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Sample records for congenital myasthenic syndromes

  1. Further Observations in Congenital Myasthenic Syndromes

    PubMed Central

    Engel, Andrew G.; Shen, Xin-Ming; Selcen, Duygu; Sine, Steven M.

    2012-01-01

    During the past five years many patients suffering from congenital myasthenic syndromes (CMS) have been identified worldwide and novel causative genes and mutations have been discovered. The disease genes now include those encoding each subunit of the acetylcholine receptor (AChR), the ColQ part of acetylcholinesterase (AChE), choline acetyltransferase, Nav 1.4, MuSK, and Dok-7. Moreover, emerging genotype-phenotype correlations are providing clues for targeted mutation analysis. This review focuses on the recent observations in selected CMS. PMID:18567859

  2. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment

    PubMed Central

    Engel, Andrew G.; Shen, Xin-Ming; Selcen, Duygu; Sine, Steven M.

    2015-01-01

    The congenital myasthenic syndromes are diverse disorders linked by abnormal signal transmission at the motor endplate that stem from defects in single or multiple proteins. Multiple endplate proteins are affected by mutations of single enzymes required for protein glycosylation, and deletion of PREPL exerts its effect by activating adaptor protein 1. Finally, neuromuscular transmission is also impaired in some congenital myopathies. The specific diagnosis of some syndromes is facilitated by clinical clues pointing to a disease gene. In absence of such clues, exome sequencing is a useful tool for finding the disease gene. Deeper understanding of disease mechanisms come from structural and in vitro electrophysiologic studies of the patient endplate, and from engineering the mutant and wild-type gene into a suitable expression system that can be interrogated by appropriate electrophysiologic and biochemical studies. Most CMS are treatable. Importantly, however, some medication beneficial in one syndrome can be detrimental in another. PMID:25792100

  3. A case of congenital myasthenic syndrome with episodic apnea

    PubMed Central

    Mallory, Leah A.; Shaw, James G.; Burgess, Stephanie L.; Estrella, Elicia; Nurko, Samuel; Burpee, Tyler M.; Agus, Michael S.; Darras, Basil T.; Kunkel, Louis M.; Kang, Peter B.

    2009-01-01

    Congenital myasthenic syndrome is difficult to diagnose, especially in the neonate when classic myasthenic signs may not be present. Congenital myasthenic syndrome with episodic apnea is a rare cause of recurrent apnea in infancy. We present an infant with nine severe episodes of apnea in the first six months of life who underwent a prolonged evaluation before ptosis was observed, leading to the diagnosis of choline acetyltransferase deficiency, a form of congenital myasthenic syndrome. Midazolam appeared to resolve the apnea on five occasions. The diagnosis was supported by edrophonium testing and repetitive nerve stimulation. Mutation analysis demonstrated compound heterozygous p. T354M and p. A557T mutations, the latter of which is novel. The patient’s respiratory status stabilized on pyridostigmine, and she is ambulatory at 3 years. Pyridostigmine is the primary therapy for choline acetyltransferase deficiency, but the observation of the efficacy of midazolam during this patient’s episodes of apnea is interesting, and bears further study. PMID:19520274

  4. Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome

    PubMed Central

    O’Connor, Emily; Töpf, Ana; Müller, Juliane S.; Cox, Daniel; Evangelista, Teresinha; Colomer, Jaume; Abicht, Angela; Senderek, Jan; Hasselmann, Oswald; Yaramis, Ahmet; Laval, Steven H.

    2016-01-01

    Congenital myasthenic syndromes are a group of rare and genetically heterogenous disorders resulting from defects in the structure and function of the neuromuscular junction. Patients with congenital myasthenic syndrome exhibit fatigable muscle weakness with a variety of accompanying phenotypes depending on the protein affected. A cohort of patients with a clinical diagnosis of congenital myasthenic syndrome that lacked a genetic diagnosis underwent whole exome sequencing in order to identify genetic causation. Missense biallelic mutations in the MYO9A gene, encoding an unconventional myosin, were identified in two unrelated families. Depletion of MYO9A in NSC-34 cells revealed a direct effect of MYO9A on neuronal branching and axon guidance. Morpholino-mediated knockdown of the two MYO9A orthologues in zebrafish, myo9aa/ab, demonstrated a requirement for MYO9A in the formation of the neuromuscular junction during development. The morphants displayed shortened and abnormally branched motor axons, lack of movement within the chorion and abnormal swimming in response to tactile stimulation. We therefore conclude that MYO9A deficiency may affect the presynaptic motor axon, manifesting in congenital myasthenic syndrome. These results highlight the involvement of unconventional myosins in motor axon functionality, as well as the need to look outside traditional neuromuscular junction-specific proteins for further congenital myasthenic syndrome candidate genes. PMID:27259756

  5. Congenital Myasthenic Syndromes with Predominant Limb Girdle Weakness

    PubMed Central

    Evangelista, Teresinha; Hanna, Mike; Lochmüller, Hanns

    2015-01-01

    Abstract Congenital myasthenic syndromes are a heterogeneous group of genetically determined disorders characterized by impaired neuromuscular transmission. They usually present from birth to childhood and are characterised by exercise induced weakness and fatigability. Genotype-phenotype correlations are difficult. However, in some patients particular phenotypic aspects may point towards a specific genetic defect. The absence of ptosis and ophthalmoparesis in patients with limb-girdle weakness makes the diagnosis of a neuromuscular transmission defect particularly challenging (LG-CMS). This is illustrated by a well-documented case published by Walton in 1956. The diagnosis of LG-CMS is secured by demonstrating a neuromuscular transmission defect with single fibre EMG or repetitive nerve stimulation, in the absence of auto-antibodies. Ultimately, a genetic test is required to identify the underlying cause and assure counselling and optimization of treatment. LG-CMS are inherited in autosomal recessive traits, and are often associated with mutations in DOK7 and GFPT1, and less frequently with mutations in COLQ, ALG2, ALG14 and DPAGT. Genetic characterization of CMS is of the upmost importance when choosing the adequate treatment. Some of the currently used drugs can either ameliorate or aggravate the symptoms depending on the underlying genetic defect. The drug most frequently used for the treatment of CMS is pyridostigmine an acetylcholinesterase inhibitor. However, pyridostigmine is not effective or is even detrimental in DOK7- and COLQ-related LG-CMS, while beta-adrenergic agonists (ephedrine, salbutamol) show some sustained benefit. Standard clinical trials may be difficult, but standardized follow-up of patients and international collaboration may help to improve the standards of care of these conditions. PMID:26870666

  6. Mutations in DPAGT1 Cause a Limb-Girdle Congenital Myasthenic Syndrome with Tubular Aggregates

    PubMed Central

    Belaya, Katsiaryna; Finlayson, Sarah; Slater, Clarke R.; Cossins, Judith; Liu, Wei Wei; Maxwell, Susan; McGowan, Simon J.; Maslau, Siarhei; Twigg, Stephen R.F.; Walls, Timothy J.; Pascual Pascual, Samuel I.; Palace, Jacqueline; Beeson, David

    2012-01-01

    Congenital myasthenic syndromes are a heterogeneous group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle weakness. We performed whole-exome sequencing to determine the underlying defect in a group of individuals with an inherited limb-girdle pattern of myasthenic weakness. We identify DPAGT1 as a gene in which mutations cause a congenital myasthenic syndrome. We describe seven different mutations found in five individuals with DPAGT1 mutations. The affected individuals share a number of common clinical features, including involvement of proximal limb muscles, response to treatment with cholinesterase inhibitors and 3,4-diaminopyridine, and the presence of tubular aggregates in muscle biopsies. Analyses of motor endplates from two of the individuals demonstrate a severe reduction of endplate acetylcholine receptors. DPAGT1 is an essential enzyme catalyzing the first committed step of N-linked protein glycosylation. Our findings underscore the importance of N-linked protein glycosylation for proper functioning of the neuromuscular junction. Using the DPAGT1-specific inhibitor tunicamycin, we show that DPAGT1 is required for efficient glycosylation of acetylcholine-receptor subunits and for efficient export of acetylcholine receptors to the cell surface. We suggest that the primary pathogenic mechanism of DPAGT1 mutations is reduced levels of acetylcholine receptors at the endplate region. These individuals share clinical features similar to those of congenital myasthenic syndrome due to GFPT1 mutations, and their disorder might be part of a larger subgroup comprising the congenital myasthenic syndromes that result from defects in the N-linked glycosylation pathway and that manifest through impaired neuromuscular transmission. PMID:22742743

  7. Salbutamol benefits children with congenital myasthenic syndrome due to DOK7 mutations.

    PubMed

    Burke, Georgina; Hiscock, Andrew; Klein, Andrea; Niks, Erik H; Main, Marion; Manzur, Adnan Y; Ng, Joanne; de Vile, Catherine; Muntoni, Francesco; Beeson, David; Robb, Stephanie

    2013-02-01

    Congenital myasthenic syndromes due to DOK7 mutations cause fatigable limb girdle weakness. Treatment with ephedrine improves muscle strength. Salbutamol, a β(2)-adrenergic receptor agonist with fewer side effects and more readily available, has been effective in adult and anecdotal childhood cases. This study reports the effects of salbutamol on motor function in childhood DOK7 congenital myasthenic syndrome. Nine children (age range 5.9-15.1years) were treated with oral salbutamol, 2-4mg TDS. The effect on timed tests of motor function, pre- and up to 28months post-treatment, was audited retrospectively. All 9 reported functional benefit within 1month, with progressive improvement to a plateau at 12-18months. Within the first month, all 3 non-ambulant children resumed walking with assistance. Although improvements were seen in some timed tests (timed 10m, arm raise time, 6min walk time) this did not fully reflect the observed functional benefits in daily living activities. No major side effects were reported. We conclude that oral salbutamol treatment significantly improves strength in children with DOK7 congenital myasthenic syndrome and is well tolerated. Outcome measures need to be refined further, both to accurately reflect functional abilities in children and to document progress and treatment response.

  8. A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis

    PubMed Central

    Habbout, Karima; Poulin, Hugo; Rivier, François; Giuliano, Serena; Sternberg, Damien; Fontaine, Bertrand; Eymard, Bruno; Morales, Raul Juntas; Echenne, Bernard; King, Louise; Hanna, Michael G.; Männikkö, Roope; Chahine, Mohamed; Nicole, Sophie

    2016-01-01

    Objective: To determine the molecular basis of a complex phenotype of congenital muscle weakness observed in an isolated but consanguineous patient. Methods: The proband was evaluated clinically and neurophysiologically over a period of 15 years. Genetic testing of candidate genes was performed. Functional characterization of the candidate mutation was done in mammalian cell background using whole cell patch clamp technique. Results: The proband had fatigable muscle weakness characteristic of congenital myasthenic syndrome with acute and reversible attacks of most severe muscle weakness as observed in periodic paralysis. We identified a novel homozygous SCN4A mutation (p.R1454W) linked to this recessively inherited phenotype. The p.R1454W substitution induced an important enhancement of fast and slow inactivation, a slower recovery for these inactivated states, and a frequency-dependent regulation of Nav1.4 channels in the heterologous expression system. Conclusion: We identified a novel loss-of-function mutation of Nav1.4 that leads to a recessive phenotype combining clinical symptoms and signs of congenital myasthenic syndrome and periodic paralysis, probably by decreasing channel availability for muscle action potential genesis at the neuromuscular junction and propagation along the sarcolemma. PMID:26659129

  9. Decoding Pathogenesis of Slow-Channel Congenital Myasthenic Syndromes using Recombinant Expression and Mice Models

    PubMed Central

    Otero-Cruz, José David; Báez-Pagán, Carlos Alberto; Dorna-Pérez, Luisamari; Grajales-Reyes, Gary Emanuel; Ramírez-Ordoñez, Rosaura Teresa; Luciano, Carlos A.; Gómez, Christopher Manuel; Lasalde-Dominicci, José Antonio

    2010-01-01

    Despite the fact that they are orphan diseases, congenital myasthenic syndromes (CMS) challenge those who suffer from it by causing fatigable muscle weakness, in the most benign cases, to a progressive wasting of muscles that may sentence patients to a wheelchair or even death. Compared to other more common neurological diseases, CMS are rare. Nevertheless, extensive research in CMS is performed in laboratories such as ours. Among the diverse neuromuscular disorders of CMS, we are focusing in the slow-channel congenital myasthenic syndrome (SCS), which is caused by mutations in genes encoding acetylcholine receptor subunits. The study of SCS has evolved from clinical electrophysiological studies to in vitro expression systems and transgenic mice models. The present review evaluates the methodological approaches that are most commonly employed to assess synaptic impairment in SCS and also provides perspectives for new approaches. Electrophysiological methodologies typically employed by physicians to diagnose patients include electromyography, whereas patient muscle samples are used for intracellular recordings, single-channel recordings and toxin binding experiments. In vitro expression systems allow the study of a particular mutation without the need of patient intervention. Indeed, in vitro expression systems have usually been implicated in the development of therapeutic strategies such as quinidine- and fluoxetine-based treatments and, more recently, RNA interference. A breakthrough in the study of SCS has been the development of transgenic mice bearing the mutations that cause SCS. These transgenic mice models have actually been key in the elucidation of the pathogenesis of the SCS mutations by linking IP-3 receptors to calcium overloading, as well as caspases and calpains to the hallmark of SCS, namely endplate myopathy. Finally, we summarize our experiences with suspected SCS patients from a local perspective and comment on one aspect of the contribution of

  10. Fundamental Gating Mechanism of Nicotinic Receptor Channel Revealed by Mutation Causing a Congenital Myasthenic Syndrome

    PubMed Central

    Wang, Hai-Long; Ohno, Kinji; Milone, Margherita; Brengman, Joan M.; Evoli, Amelia; Batocchi, Anna-Paola; Middleton, Lefkos T.; Christodoulou, Kyproula; Engel, Andrew G.; Sine, Steven M.

    2000-01-01

    We describe the genetic and kinetic defects in a congenital myasthenic syndrome due to the mutation εA411P in the amphipathic helix of the acetylcholine receptor (AChR) ε subunit. Myasthenic patients from three unrelated families are either homozygous for εA411P or are heterozygous and harbor a null mutation in the second ε allele, indicating that εA411P is recessive. We expressed human AChRs containing wild-type or A411P ε subunits in 293HEK cells, recorded single channel currents at high bandwidth, and determined microscopic rate constants for individual channels using hidden Markov modeling. For individual wild-type and mutant channels, each rate constant distributes as a Gaussian function, but the spread in the distributions for channel opening and closing rate constants is greatly expanded by εA411P. Prolines engineered into positions flanking residue 411 of the ε subunit greatly increase the range of activation kinetics similar to εA411P, whereas prolines engineered into positions equivalent to εA411 in β and δ subunits are without effect. Thus, the amphipathic helix of the ε subunit stabilizes the channel, minimizing the number and range of kinetic modes accessible to individual AChRs. The findings suggest that analogous stabilizing structures are present in other ion channels, and possibly allosteric proteins in general, and that they evolved to maintain uniformity of activation episodes. The findings further suggest that the fundamental gating mechanism of the AChR channel can be explained by a corrugated energy landscape superimposed on a steeply sloped energy well. PMID:10962020

  11. A Novel Missense Variant in the AGRN Gene; Congenital Myasthenic Syndrome Presenting With Head Drop.

    PubMed

    Karakaya, Mert; Ceyhan-Birsoy, Ozge; Beggs, Alan H; Topaloglu, Haluk

    2017-03-01

    Congenital myasthenic syndromes (CMS) are a heterogeneous group of diseases of the neuromuscular junction caused by compromised synaptic transmission. Clinical features include early-onset weakness of limbs and oculobulbar muscles resulting in hypotonia, bulbar paresis, ptosis, and hypoventilation. The first dropped head syndrome in children were detected in 2 patients with LMNA and SEPN1 mutations. We report a 17-month-old boy with dropped head and limb-girdle weakness, who had no ptosis or ophthalmoplegia at presentation. We performed whole exome sequencing, which revealed a homozygous missense variant in the AGRN gene c.5023G>A, p.Gly1675Ser in the LG2 domain, which is predicted to be likely disease causing by in silico tools. Agrin is known to play a critical role in the development and maintenance of the neuromuscular junction. Agrin-related CMS is one of the rarest subtypes. Of note, our patient is the first described patient with agrin-related CMS with dropped head phenotype.

  12. A synonymous CHRNE mutation responsible for an aberrant splicing leading to congenital myasthenic syndrome.

    PubMed

    Richard, Pascale; Gaudon, Karen; Fournier, Emmanuel; Jackson, Christopher; Bauché, Stéphanie; Haddad, Hafedh; Koenig, Jeanine; Echenne, Bernard; Hantaï, Daniel; Eymard, Bruno

    2007-05-01

    Congenital myasthenic syndromes (CMSs) are rare hereditary disorders transmitted in a recessive or dominant pattern, and are caused by mutations in the genes encoding proteins of the neuromuscular junction. They are classified in three groups depending on the origin of the molecular defect. Postsynaptic defects are the most frequent and have been reported to be partly due to abnormalities of the acetylcholine receptor, and particularly to mutations in CHRNE, the gene encoding the acetylcholine receptor epsilon-subunit. In a Portuguese patient with a mild form of recessive CMS, CHRNE sequencing identified an unknown homozygous transition. This variation affects the third nucleotide of the glycine 285 condon, and leads to a synonymous variant. Analysis of transcripts demonstrated that this single change creates a new splice donor site located 4 nucleotides upstream of the normal site, leading to a deletion and generating a frameshift in exon 9 followed by a premature termination codon. This paper relates the identification of a synonymous mutation in CHRNE that creates a new splice donor site leading to an aberrant splicing of pre-mRNAs and so to their instability. This is the first synonymous mutation in CHRNE known to generate a cryptic splice site, and mRNA quantification strongly suggests that it is the disease-causing mutation.

  13. Defective Fast Inactivation Recovery of Nav1.4 in Congenital Myasthenic Syndrome

    PubMed Central

    Arnold, W. David; Feldman, Daniel H.; Ramirez, Sandra; He, Liuyuan; Kassar, Darine; Quick, Adam; Klassen, Tara L.; Lara, Marian; Nguyen, Joanna; Kissel, John T.; Lossin, Christoph; Maselli, Ricardo A.

    2015-01-01

    Objective To describe the unique phenotype and genetic findings in a 57-year-old female with a rare form of congenital myasthenic syndrome (CMS) associated with longstanding muscle fatigability, and to investigate the underlying pathophysiology. Methods We used whole-cell voltage clamping to compare the biophysical parameters of wild-type and Arg1457His-mutant Nav1.4. Results Clinical and neurophysiological evaluation revealed features consistent with CMS. Sequencing of candidate genes indicated no abnormalities. However, analysis of SCN4A, the gene encoding the skeletal muscle sodium channel Nav1.4, revealed a homozygous mutation predicting an arginine-to-histidine substitution at position 1457 (Arg1457His), which maps to the channel’s voltage sensor, specifically D4/S4. Whole-cell patch clamp studies revealed that the mutant required longer hyperpolarization to recover from fast inactivation, which produced a profound use-dependent current attenuation not seen in the wild type. The mutant channel also had a marked hyperpolarizing shift in its voltage dependence of inactivation as well as slowed inactivation kinetics. Interpretation We conclude that Arg1457His compromises muscle fiber excitability. The mutant fast-inactivates with significantly less depolarization, and it recovers only after extended hyperpolarization. The resulting enhancement in its use dependence reduces channel availability, which explains the patient’s muscle fatigability. Arg1457His offers molecular insight into a rare form of CMS precipitated by sodium channel inactivation defects. Given this channel’s involvement in other muscle disorders such as paramyotonia congenita and hyperkalemic periodic paralysis, our study exemplifies how variations within the same gene can give rise to multiple distinct dysfunctions and phenotypes, revealing residues important in basic channel function. PMID:25707578

  14. Choline Acetyltransferase Mutations Causing Congenital Myasthenic Syndrome: Molecular Findings and Genotype-Phenotype Correlations.

    PubMed

    Arredondo, Juan; Lara, Marian; Gospe, Sídney M; Mazia, Claudio G; Vaccarezza, Maria; Garcia-Erro, Marcela; Bowe, Constance M; Chang, Celia H; Mezei, Michelle M; Maselli, Ricardo A

    2015-09-01

    Choline acetyltransferase catalyzes the synthesis of acetylcholine at cholinergic nerves. Mutations in human CHAT cause a congenital myasthenic syndrome due to impaired synthesis of ACh; this severe variant of the disease is frequently associated with unexpected episodes of potentially fatal apnea. The severity of this condition varies remarkably, and the molecular factors determining this variability are poorly understood. Furthermore, genotype-phenotype correlations have been difficult to establish in patients with biallelic mutations. We analyzed the protein expression of phosphorylated ChAT of seven CHAT mutations, p.Val136Met, p.Arg207His, p.Arg186Trp, p.Val194Leu, p.Pro211Ala, p.Arg566Cys, and p.Ser694Cys, in HEK-293 cells to phosphorylated ChAT, determined their enzyme kinetics and thermal stability, and examined their structural changes. Three mutations, p.Arg207His, p.Arg186Trp, and p.Arg566Cys, are novel, and p.Val136Met and p.Arg207His are homozygous in three families and associated with severe disease. The characterization of mutants showed a decrease in the overall catalytic efficiency of ChAT; in particular, those located near the active-site tunnel produced the most seriously disruptive phenotypic effects. On the other hand, p.Val136Met, which is located far from both active and substrate-binding sites, produced the most drastic reduction of ChAT expression. Overall, CHAT mutations producing low enzyme expression and severe kinetic effects are associated with the most severe phenotypes.

  15. Choline acetyltransferase mutations causing congenital myasthenic syndrome: molecular findings and genotype-phenotype correlations

    PubMed Central

    Arredondo, Juan; Lara, Marian; Gospe, Sídney M.; Mazia, Claudio G.; Vaccarezza, Maria; Garcia-Erro, Marcela; Bowe, Constance; Chang, Celia; Mezei, Michelle; Maselli, Ricardo A.

    2015-01-01

    Choline acetyltransferase catalyzes the synthesis of acetylcholine at cholinergic nerves. Mutations in human CHAT cause a congenital myasthenic syndrome (CMS) due to impaired synthesis of ACh; this severe variant of the disease is frequently associated with unexpected episodes of potentially fatal apnea. The severity of this condition varies remarkably, and the molecular factors determining this variability are poorly understood. Furthermore, genotype–phenotype correlations have been difficult to establish in patients with biallelic mutations. We analyzed the protein expression of seven ChAT mutations, p.Val136Met, p.Arg207His, p.Arg186Trp, p.Val194Leu, p.Pro211Ala, p.Arg566Cys and p.Ser694Cys, in HEK-293 cells to phosphorylated ChAT, determined their enzyme kinetics and thermal instability, and examined their structural changes. Three mutations, p.Arg207His, p.Arg186Trp and p.Arg566Cys, are novel, and p.Val136Met and p.Arg207His are homozygous in three families and associated with severe disease. The characterization of mutants showed a decrease in the overall catalytic efficiency of ChAT; in particular, those located near the active-site tunnel produced the most seriously disruptive phenotypic effects. On the other hand, p.Val136Met is located far from both active and substrate-binding sites produced the most drastic reduction of ChAT expression. Overall, CHAT mutations producing low enzyme expression and severe kinetic effects are associated with the most severe phenotypes. PMID:26080897

  16. A COLQ Missense Mutation in Sphynx and Devon Rex Cats with Congenital Myasthenic Syndrome

    PubMed Central

    Abitbol, Marie; Hitte, Christophe; Bossé, Philippe; Blanchard-Gutton, Nicolas; Thomas, Anne; Martignat, Lionel; Blot, Stéphane; Tiret, Laurent

    2015-01-01

    An autosomal recessive neuromuscular disorder characterized by skeletal muscle weakness, fatigability and variable electromyographic or muscular histopathological features has been described in the two related Sphynx and Devon Rex cat breeds (Felis catus). Collection of data from two affected Sphynx cats and their relatives pointed out a single disease candidate region on feline chromosome C2, identified following a genome-wide SNP-based homozygosity mapping strategy. In that region, we further identified COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase) as a good candidate gene, since COLQ mutations were identified in affected humans and dogs with endplate acetylcholinesterase deficiency leading to a synaptic form of congenital myasthenic syndrome (CMS). A homozygous c.1190G>A missense variant located in exon 15 of COLQ, leading to a C397Y substitution, was identified in the two affected cats. C397 is a highly-conserved residue from the C-terminal domain of the protein; its mutation was previously shown to produce CMS in humans, and here we confirmed in an affected Sphynx cat that it induces a loss of acetylcholinesterase clustering at the neuromuscular junction. Segregation of the c.1190G>A variant was 100% consistent with the autosomal recessive mode of inheritance of the disorder in our cat pedigree; in addition, an affected, unrelated Devon Rex cat recruited thereafter was also homozygous for the variant. Genotyping of a panel of 333 cats from 14 breeds failed to identify a single carrier in non-Sphynx and non-Devon Rex cats. Finally, the percentage of healthy carriers in a European subpanel of 81 genotyped Sphynx cats was estimated to be low (3.7%) and 14 control Devon Rex cats were genotyped as wild-type individuals. Altogether, these results strongly support that the neuromuscular disorder reported in Sphynx and Devon Rex breeds is a CMS caused by a unique c.1190G>A missense mutation, presumably transmitted through a founder effect, which

  17. Fast-channel congenital myasthenic syndrome with a novel acetylcholine receptor mutation at the α-ε subunit interface.

    PubMed

    Webster, Richard; Liu, Wei-Wei; Chaouch, Amina; Lochmüller, Hanns; Beeson, David

    2014-02-01

    Congenital myasthenic syndromes (CMS) result from the failure to achieve muscle depolarisation due to disorders in the structure and/or function of the neuromuscular synapse. Mutations of the nicotinic acetylcholine receptor (nAChR) form a major subset of CMS. We describe a patient who presented with recurrent apnoeic crises in the neonatal period requiring ventilator support. Electromyography revealed compound muscle action potential decrement upon repetitive stimulation. Sequencing of nAChR subunit genes revealed two missense mutations. One previously reported null mutation p.εTyr15His, and a second novel missense mutation, p.εThr38Lys, that is well expressed in mammalian cell culture and thus likely to exert its effect via alteration of ion channel kinetics. Functional analysis revealed abbreviated ion channel bursts characteristic of a fast channel CMS. The mutation p.εThr38Lys occurs at the interface between the α and ε subunits of the nAChR pentamer and leads to instability of the open channel. The effects of this mutation on channel function were investigated in relation to other fast channel mutants at an analogous subunit interface within the nAChR pentamer. Fast channel syndromes are frequently characterised by severe myasthenic weakness with apnoeic crises; knowledge of the underlying mutation and its functional consequences can be vital for appropriate therapy and patient management.

  18. Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic).

    PubMed Central

    Donger, C; Krejci, E; Serradell, A P; Eymard, B; Bon, S; Nicole, S; Chateau, D; Gary, F; Fardeau, M; Massoulié, J; Guicheney, P

    1998-01-01

    Congenital myasthenic syndrome (CMS) with end-plate acetylcholinesterase (AChE) deficiency is a rare autosomal recessive disease, recently classified as CMS type Ic (CMS-Ic). It is characterized by onset in childhood, generalized weakness increased by exertion, refractoriness to anticholinesterase drugs, and morphological abnormalities of the neuromuscular junctions (NMJs). The collagen-tailed form of AChE, which is normally concentrated at NMJs, is composed of catalytic tetramers associated with a specific collagen, COLQ. In CMS-Ic patients, these collagen-tailed forms are often absent. We studied a large family comprising 11 siblings, 6 of whom are affected by a mild form of CMS-Ic. The muscles of the patients contained collagen-tailed AChE. We first excluded the ACHE gene (7q22) as potential culprit, by linkage analysis; then we mapped COLQ to chromosome 3p24.2. By analyzing 3p24.2 markers located close to the gene, we found that the six affected patients were homozygous for an interval of 14 cM between D3S1597 and D3S2338. We determined the COLQ coding sequence and found that the patients present a homozygous missense mutation, Y431S, in the conserved C-terminal domain of COLQ. This mutation is thought to disturb the attachment of collagen-tailed AChE to the NMJ, thus constituting the first genetic defect causing CMS-Ic. PMID:9758617

  19. Myasthenia Gravis and the Myasthenic Syndrome

    PubMed Central

    Herrmann, Christian

    1970-01-01

    Two disorders of neuromuscular transmission producing muscle weakness and easy fatigability which may confront the physician are myasthenia gravis and the myasthenic syndrome. The former has early symptoms and signs of oculobulbar and then extremity weakness with rapid decline of action potential and contractile strength with repetitive use and nerve-muscle stimulation. Anticholinesterases improve strength. The myasthenic syndrome has early symptoms and signs of pelvic girdle, pectoral girdle and proximal limb muscle weakness. This is worst when first starting to use or carry out nerve muscle stimulation in the rested muscles. It improves significantly for a time with use or on rapid stimulation, and then declines with continued activation. Deep tendon reflexes are sluggish or absent. Small cell carcinoma of the lung is often associated. Guanidine improves the strength. Other features and possible underlying mechanisms of the two disorders help to differentiate and treat them. PMID:5457513

  20. Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1)

    PubMed Central

    Chen, Qiushi; Müller, Juliane S.; Pang, Poh-Choo; Laval, Steve H.; Haslam, Stuart M.; Lochmüller, Hanns; Dell, Anne

    2015-01-01

    Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first enzyme of the hexosamine biosynthetic pathway. It transfers an amino group from glutamine to fructose-6-phosphate to yield glucosamine-6-phosphate, thus providing the precursor for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is an essential substrate for all mammalian glycosylation biosynthetic pathways and N-glycan branching is especially sensitive to alterations in the concentration of this sugar nucleotide. It has been reported that GFPT1 mutations lead to a distinct sub-class of congenital myasthenic syndromes (CMS) termed “limb-girdle CMS with tubular aggregates”. CMS are hereditary neuromuscular transmission disorders in which neuromuscular junctions are impaired. To investigate whether alterations in protein glycosylation at the neuromuscular junction might be involved in this impairment, we have employed mass spectrometric strategies to study the N-glycomes of myoblasts and myotubes derived from two healthy controls, three GFPT1 patients, and four patients with other muscular diseases, namely CMS caused by mutations in DOK7, myopathy caused by mutations in MTND5, limb girdle muscular dystrophy type 2A (LGMD2A), and Pompe disease. A comparison of the relative abundances of bi-, tri-, and tetra-antennary N-glycans in each of the cell preparations revealed that all samples exhibited broadly similar levels of branching. Moreover, although some differences were observed in the relative abundances of some of the N-glycan constituents, these variations were modest and were not confined to the GFPT1 samples. Therefore, GFPT1 mutations in CMS patients do not appear to compromise global N-glycosylation in muscle cells. PMID:26501342

  1. Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1).

    PubMed

    Chen, Qiushi; Müller, Juliane S; Pang, Poh-Choo; Laval, Steve H; Haslam, Stuart M; Lochmüller, Hanns; Dell, Anne

    2015-10-16

    Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first enzyme of the hexosamine biosynthetic pathway. It transfers an amino group from glutamine to fructose-6-phosphate to yield glucosamine-6-phosphate, thus providing the precursor for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is an essential substrate for all mammalian glycosylation biosynthetic pathways and N-glycan branching is especially sensitive to alterations in the concentration of this sugar nucleotide. It has been reported that GFPT1 mutations lead to a distinct sub-class of congenital myasthenic syndromes (CMS) termed "limb-girdle CMS with tubular aggregates". CMS are hereditary neuromuscular transmission disorders in which neuromuscular junctions are impaired. To investigate whether alterations in protein glycosylation at the neuromuscular junction might be involved in this impairment, we have employed mass spectrometric strategies to study the N-glycomes of myoblasts and myotubes derived from two healthy controls, three GFPT1 patients, and four patients with other muscular diseases, namely CMS caused by mutations in DOK7, myopathy caused by mutations in MTND5, limb girdle muscular dystrophy type 2A (LGMD2A), and Pompe disease. A comparison of the relative abundances of bi-, tri-, and tetra-antennary N-glycans in each of the cell preparations revealed that all samples exhibited broadly similar levels of branching. Moreover, although some differences were observed in the relative abundances of some of the N-glycan constituents, these variations were modest and were not confined to the GFPT1 samples. Therefore, GFPT1 mutations in CMS patients do not appear to compromise global N-glycosylation in muscle cells.

  2. "Dropped head syndrome" caused by Lambert-Eaton myasthenic syndrome.

    PubMed

    Ueda, T; Kanda, F; Kobessho, H; Hamaguchi, H; Motomura, M

    2009-07-01

    A 67-year-old man was admitted with a 2-year history of dropped head. Neurological examination revealed ptosis, dysarthria, neck weakness, hyporeflexia of all limbs, and autonomic failure. Electrophysiologic study showed a 400% increment response to high-rate repetitive nerve stimulation. Serum anti-P/Q-voltage-gated calcium channel antibody was positive, confirming the diagnosis of Lambert-Eaton myasthenic syndrome (LEMS). His symptoms and electrophysiological abnormalities improved with oral prednisolone following plasmapheresis. This is the first report of LEMS as a cause of dropped head syndrome.

  3. Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome & Congenital Myasthenic Syndromes

    MedlinePlus

    ... treatment plan, adjust to your diagnosis and take control in maintaining the quality of your life. This pamphlet will provide you with essential information about the symptoms of MG and the best treatments ... control breathing, MG usually doesn’t shorten life expectancy. ...

  4. Presynaptic Disorders: Lambert-Eaton Myasthenic Syndrome and Botulism.

    PubMed

    Gable, Karissa L; Massey, Janice M

    2015-08-01

    Lambert-Eaton myasthenic syndrome (LEMS) and botulism are acquired presynaptic nerve terminal disorders of the neuromuscular junction. Lambert-Eaton myasthenic syndrome is an idiopathic or paraneoplastic autoimmune syndrome in which autoantibodies of the P/Q-type voltage-gated calcium channel play a role in decreasing the release of acetylcholine, resulting in clinical symptoms of skeletal muscle weakness, diminished reflexes, and autonomic symptoms. Paraneoplastic LEMS is most often associated with small cell lung cancer. Diagnosis is confirmed by positive serologic testing and electrophysiological studies, which display characteristic features of low compound muscle action potentials, a decrement at 3Hz repetitive nerve stimulation, and facilitation with exercise or high-frequency repetitive stimulation. Treatment involves cancer monitoring and treatment, 3,4-diaminopyridine, immunosuppressive medications, and acetylcholinesterase inhibitors. Botulism is another presynaptic disorder of neuromuscular transmission. Clinical features classically involve cranial and bulbar palsies followed by descending weakness of the limbs, respiratory failure, and autonomic dysfunction. Electrodiagnostic testing is important in the evaluation and diagnosis. Treatment is supportive, and administration of antitoxin is beneficial in selected cases.

  5. A mouse model of the slow channel myasthenic syndrome: Neuromuscular physiology and effects of ephedrine treatment.

    PubMed

    Webster, R G; Cossins, J; Lashley, D; Maxwell, S; Liu, W W; Wickens, J R; Martinez-Martinez, P; de Baets, M; Beeson, D

    2013-10-01

    In the slow channel congenital myasthenic syndrome mutations in genes encoding the muscle acetylcholine receptor give rise to prolonged ion channel activations. The resulting cation overload in the postsynaptic region leads to damage of synaptic structures, impaired neuromuscular transmission and fatigable muscle weakness. Previously we identified and characterised in detail the properties of the slow channel syndrome mutation εL221F. Here, using this mutation, we generate a transgenic mouse model for the slow channel syndrome that expresses mutant human ε-subunits harbouring an EGFP tag within the M3-M4 cytoplasmic region, driven by a ~1500 bp region of the CHRNB promoter. Fluorescent mutant acetylcholine receptors are assembled, cluster at the motor endplates and give rise to a disease model that mirrors the human condition. Mice demonstrate mild fatigable muscle weakness, prolonged endplate and miniature endplate potentials, and variable degeneration of the postsynaptic membrane. We use our model to investigate ephedrine as a potential treatment. Mice were assessed before and after six weeks on oral ephedrine (serum ephedrine concentration 89 ± 3 ng/ml) using an inverted screen test and in vivo electromyography. Treated mice demonstrated modest benefit for screen hang time, and in measures of compound muscle action potentials and mean jitter that did not reach statistical significance. Ephedrine and salbutamol show clear benefit when used in the treatment of DOK7 or COLQ congenital myasthenic syndromes. Our results highlight only a modest potential benefit of these β2-adrenergic receptor agonists for the treatment of the slow channel syndrome.

  6. Genetics Home Reference: congenital myasthenic syndrome

    MedlinePlus

    ... However, any of the muscles used for movement ( skeletal muscles ) can be affected in this condition. Due to ... cells results in an impaired ability to move skeletal muscles , muscle weakness, and delayed development of motor skills. ...

  7. Myasthenic syndrome of snake envenomation: a clinical and neurophysiological study.

    PubMed Central

    Sanmuganathan, P. S.

    1998-01-01

    In this prospective study, 65 consecutive patients with neurological manifestations after snake envenomation, were examined in order to describe the natural history of the reversible nature of muscle weakness. Snake envenoming led to a completely reversible muscle paralysis involving the external ocular muscles with sparing of the pupils, muscles of mastication, facial muscles, palatal muscles, neck and proximal limb muscles. The deep tendon reflexes were preserved with no sensory abnormalities. The muscular weakness usually set in within an hour of envenomation and lasted up to 10 days, with fatigability lasting for 12 days. Respiratory muscle paralysis led to ventilatory failure needing ventilation in severely envenomed patients. Motor and sensory nerve conduction were normal with normal resting compound motor action potentials on electromyography. Repetitive nerve stimulation gave rise to a decremental response during high frequency stimulation. The edrophonium test gave negative results. These manifestations are due to abnormalities of neuromuscular transmission and are not typical of myasthenia gravis. As the exact pathophysiology of venom-related neurotoxicity is not known, it is suggested that the neurological manifestations of snake envenoming be designated a myasthenic syndrome. Further studies to isolate the neurotoxin and its mechanism and exact site of blocking at the neuromuscular junction would pave the way for the development of a novel long-acting neuromuscular blocking agent. Images Figure 1 Figure 2 Figure 3 PMID:10211352

  8. Distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome

    PubMed Central

    Maddison, P.; Newsom-Davis, J.; Mills, K.

    1998-01-01

    OBJECTIVE—To assess the distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome (LEMS) to identify the most sensitive muscle to use in routine examination.
METHODS—Surface recorded compound muscle action potential (CMAP) amplitudes were made from abductor digiti minimi, abductor pollicis brevis, anconeus, biceps brachii, and trapezius in 10 patients with LEMS. The effect of 3,4-diaminopyridine (3,4-DAP) was recorded in each muscle in nine patients. CMAP amplitudes were measured at rest and immediately after 10 seconds maximal voluntary contraction in each muscle. Values were compared with results obtained from 12 healthy controls.
RESULTS—Resting CMAP amplitudes were reduced in at least one muscle in all patients compared with controls, most markedly in abductor digiti minimi and anconeus. The administration of 3,4-DAP resulted in significantly improved resting CMAP amplitudes in trapezius only. After maximal voluntary muscle contraction, characteristic increments in CMAP amplitude of over 100% above resting values were seen in abductor digiti minimi and abductor pollicis brevis in seven patients, anconeus and biceps brachii in five patients. No patient had this level of increment in trapezius.
CONCLUSION—Despite predominantly proximal limb weakness seen clinically in patients with LEMS, the most sensitive muscles for detecting characteristic electrophysiological abnormalities of low resting CMAP amplitude and increment of over 100% after 10 seconds maximal voluntary contraction are abductor digiti minimi, abductor pollicis brevis, and anconeus.

 PMID:9703174

  9. Congenital nephrotic syndrome

    MedlinePlus

    ... may be high. There may be signs of malnutrition. A urinalysis reveals fat and large amounts of ... The disorder often leads to infection, malnutrition, and kidney failure. ... die within the first year. Congenital nephrotic syndrome ...

  10. Simultaneous Combined Myositis, Inflammatory Polyneuropathy, and Overlap Myasthenic Syndrome

    PubMed Central

    Magy, Laurent; Corcia, Philippe; Ghorab, Karima; Richard, Laurence; Ciron, Jonathan; Duchesne, Mathilde; Vallat, Jean-Michel

    2016-01-01

    Immune-mediated neuromuscular disorders include pathologies of the peripheral nervous system, neuromuscular junction, and muscles. If overlap syndromes (or the association of almost two autoimmune disorders) are recognized, the simultaneous occurrence of several autoimmune neuromuscular disorders is rare. We describe two patients presenting the simultaneous occurrence of inflammatory neuropathy, myositis, and myasthenia gravis (with positive acetylcholine receptor antibodies). For each patient, we carried out a pathological analysis (nerve and muscle) and an electrophysiological study (and follow-up). To our knowledge, this is the first description of such a triple immune-mediated neuromuscular syndrome. We compared our observations with a few other cases of simultaneous diagnosis of two inflammatory neuromuscular disorders. PMID:28044116

  11. Proteasome inhibitors for malignancy-related Lambert-Eaton myasthenic syndrome.

    PubMed

    Wang, Chen; Chen, Shaobo; Feng, Bing; Guan, Yuzhou

    2014-03-01

    Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder characterized by autoantibodies against presynaptic voltage-gated calcium channels that impair neuromuscular transmission. Malignancies, especially small cell lung cancer (SCLC), have been associated with LEMS and account for approximately 60% of cases, making malignancy management a central step in LEMS therapy. In addition, immunosuppressive therapy is also recommended for symptomatic control. Interestingly, both pathological and epidemiological data suggest that the autoimmune response can inhibit progression of tumors in malignancy-associated LEMS. Thus, conventional broad-spectrum immunosuppressants may not be effective agents for treatment of LEMS, especially in those with malignancy-associated LEMS. Recent preclinical and clinical studies have indicated that proteasome inhibitors can eliminate antibody-producing cells efficiently, block dendritic cell maturation, and have anti-tumor activity. We hypothesize that proteasome inhibitors may be promising agents for treatment of malignancy-related LEMS.

  12. Myasthenia gravis and myasthenic syndrome: simulation of twitch strength with or without therapy.

    PubMed

    Nigrovic, Vladimir; Amann, Anton; Bhatt, Shashi

    2005-12-01

    To examine the quantitative relationship between indirectly evoked twitch and decreases in the number of either postsynaptic receptors or acetylcholine molecules released by a single stimulus, we studied these variables in a computer-simulated model of neuromuscular transmission. Twitch strength decreased if the number of receptors decreased to below 30% of normal or the number of acetylcholine molecules released by a stimulus decreased to below 80%. Inhibition of acetylcholine hydrolysis to 50% restored twitch strength in the presence of a decreased number of receptors. However, twitch strength was more easily restored to normalcy by augmenting the release of acetylcholine, if the release was diminished by disease. The simulations mimic the clinically known therapeutic outcomes in certain disorders of neuromuscular transmission. These results provide useful quantitative insights into the relationship between acetylcholine receptors or the stimulus-induced release of acetylcholine and muscle function in myasthenia gravis or Lambert-Eaton myasthenic syndrome.

  13. Genetics Home Reference: congenital nephrotic syndrome

    MedlinePlus

    ... 4 links) Great Ormond Street Hospital for Children (UK) MedlinePlus Encyclopedia: Congenital Nephrotic Syndrome MedlinePlus Encyclopedia: End- ... Version National Health Service: Nephrotic Syndrome in Children (UK) Orphanet: Congenital nephrotic syndrome, Finnish type Patient Support ...

  14. Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthenic syndrome.

    PubMed

    Nagashima, Toshiko; Mizutani, Yasuyuki; Kawahara, Hiromasa; Maguchi, Shiro; Terayama, Yoshihiko; Shinohara, Toshiya; Orba, Yasuko; Chuma, Takayo; Mano, Yukio; Itoh, Tomoo; Sawa, Hirofumi; Sakai, Koichiro; Motomura, Masakatsu; Nagashima, Kazuo

    2003-09-01

    Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50-year-old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. Pulmonary X-ray findings, class IIIb sputum cytology, and positive anti-Hu antibody established the diagnosis of PNS associated with small-cell lung cancer (SCLC). Two cycles of combined chemotherapy resulted in shrinkage of the lung tumor together with complete recovery of neurological symptoms and disappearance of anti-Hu antibody. Relapse of SCLC 4 months later with re-appearance of anti-Hu antibody required additional chemotherapy and irradiation. Eight months later, when multiple liver metastasis of SCLC was noticed, muscular weakness with positive waxing phenomenon compatible with Lambert-Eaton myasthenic syndrome (LEMS) developed. Postmortem examinations revealed residual SCLC in the primary lung, and massive liver metastasis with generalized lymph node involvement, but no tumors in the CNS. In the cerebellum, there was a slight loss of Purkinje cells with torpedo formation but without apparent lymphocytic infiltration. The present PNS was unique in that the relapse of SCLC was accompanied by the appearance of anti-Hu antibody, and that initial signs of brainstem-cerebellar symptoms, encephalopathy and autonomic failure were replaced by LEMS coinciding with the tumor recurrence.

  15. Conjoint occurrence of GABAB receptor antibodies in Lambert-Eaton myasthenic syndrome with antibodies to the voltage gated calcium channel.

    PubMed

    Dogan Onugoren, Müjgan; Rauschka, Helmut; Bien, Christian G

    2014-08-15

    Antibodies (abs) to the GABAB receptor have been recently found to be responsible for immune-mediated encephalitis with dominant seizures. They are in approximately 50% of cases associated with small-cell lung cancer (SCLC). GABAB receptors are mainly located in the hippocampus, thalamus and cerebellum in the presynaptic and postsynaptic regions of synapses. The main function of these receptors is to reduce activity states of neurons. In some instances, GABAB receptor abs in these patients were accompanied by other antibodies, among them VGCC abs (Lancaster et al., 2010, Boronat et al., 2011). VGCC abs cause paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) by reduction of presynaptic VGCCs (Titulaer et al., 2011). In the domain of CNS disease, VGCC abs have been found in association with paraneoplastic cerebellar ataxia (Mason et al., 1997) and rarely and at low titres also in other paraneoplastic encephalopathies together with Hu abs (Lennon et al., 1995). It has been a long-standing debate if abs in paraneoplastic conditions associate rather with the neurological syndrome or the tumour. Here, we describe the conjoint occurrence of abs to the GABAB receptor and to the VGCC in a patient with SCLC presenting only symptoms of the peripheral nervous system giving another example of the latter hypothesis.

  16. Unilateral straight hair and congenital horner syndrome.

    PubMed

    Wang, Frederick M; Wertenbaker, Christian; Cho, Hyung; Marmor, Maury A; Ahn-Lee, Sandra S; Bernard, Bruno A

    2012-06-01

    Congenital Horner syndrome is a rare disorder that accounts for less than 5% of all cases of Horner syndrome. Like Horner syndrome in general, it consists primarily of ptosis, miosis, and anhidrosis. Congenital Horner syndrome may manifest some special features such as iris heterochromia since the sympathetic nervous system is an essential component for the development and maintenance of eye color. We present 3 cases of unilateral straight hair in association with congenital Horner syndrome in which the patients had straight hair ipsilateral to the Horner syndrome, whereas on the contralateral side, it was curly, and we discuss possible mechanisms for this phenomenon.

  17. Sequential fluctuating paraneoplastic ocular flutter-opsoclonus-myoclonus syndrome and Lambert-Eaton myasthenic syndrome in small-cell lung cancer.

    PubMed

    Simister, Robert J; Ng, Karl; Lang, Bethan; Beckles, Michael; Chao, David; McCabe, Dominick J H

    2011-03-01

    Paraneoplastic cerebellar degeneration may occur in association with Lambert-Eaton myasthenic syndrome (LEMS), but to our knowledge, the co-occurrence of paraneoplastic opsoclonus-myoclonus syndrome and LEMS has not been previously reported. A 67-year-old woman presented with a complex partial seizure and evolving ocular flutter, opsoclonus, myoclonus and 'cerebellar' signs, all of which improved spontaneously within 6 weeks. Approximately 8 weeks after symptom onset, the patient became encephalopathic, she had a further complex partial seizure, and she became areflexic with potentiation of deep tendon reflexes. Radiological, bronchoscopic and histological investigations revealed small-cell lung cancer, and neurophysiological investigations confirmed a diagnosis of LEMS. High-titre anti-P/Q-type voltage-gated calcium-channel antibodies were identified in the serum, which increased as the signs of opsoclonus and myoclonus resolved. The encephalopathy and clinical features of LEMS responded dramatically to chemotherapy and radiotherapy. Spontaneous improvement of paraneoplastic opsoclonus-myoclonus syndrome may occur, and this syndrome may occur in association with LEMS. Antivoltage-gated calcium-channel antibodies are not implicated in the pathogenesis of paraneoplastic opsoclonus-myoclonus syndrome.

  18. Postural deformities in congenital nephrotic syndrome.

    PubMed Central

    Morgan, G; Postlethwaite, R J; Lendon, M; Houston, I B; Savage, J M

    1981-01-01

    Six successive cases of congenital nephrotic syndrome are described. Each one showed flexion deformities of the knees and hips, widely open anterior and posterior fontanelles, and wide separation of the skull sutures. These abnormalities were present not only in cases in which the renal histology was of the microcystic Finnish type of congenital nephrotic syndrome, but also in those in which the histological picture was one of the variants associated with congenital nephrotic syndrome. It is suggested that such abnormalities are postural deformities, possibly produced by the large placenta. Images Fig. 1 Fig. 2 PMID:7332344

  19. Genetics Home Reference: congenital central hypoventilation syndrome

    MedlinePlus

    ... on PubMed Berry-Kravis EM, Zhou L, Rand CM, Weese-Mayer DE. Congenital central hypoventilation syndrome: PHOX2B ... Abara SG, Zhou L, Berry-Kravis EM, Rand CM, Weese-Mayer DE. Later-onset congenital central hypoventilation ...

  20. Molecular Pathophysiology of Congenital Long QT Syndrome.

    PubMed

    Bohnen, M S; Peng, G; Robey, S H; Terrenoire, C; Iyer, V; Sampson, K J; Kass, R S

    2017-01-01

    Ion channels represent the molecular entities that give rise to the cardiac action potential, the fundamental cellular electrical event in the heart. The concerted function of these channels leads to normal cyclical excitation and resultant contraction of cardiac muscle. Research into cardiac ion channel regulation and mutations that underlie disease pathogenesis has greatly enhanced our knowledge of the causes and clinical management of cardiac arrhythmia. Here we review the molecular determinants, pathogenesis, and pharmacology of congenital Long QT Syndrome. We examine mechanisms of dysfunction associated with three critical cardiac currents that comprise the majority of congenital Long QT Syndrome cases: 1) IKs, the slow delayed rectifier current; 2) IKr, the rapid delayed rectifier current; and 3) INa, the voltage-dependent sodium current. Less common subtypes of congenital Long QT Syndrome affect other cardiac ionic currents that contribute to the dynamic nature of cardiac electrophysiology. Through the study of mutations that cause congenital Long QT Syndrome, the scientific community has advanced understanding of ion channel structure-function relationships, physiology, and pharmacological response to clinically employed and experimental pharmacological agents. Our understanding of congenital Long QT Syndrome continues to evolve rapidly and with great benefits: genotype-driven clinical management of the disease has improved patient care as precision medicine becomes even more a reality.

  1. Escobar syndrome mimicing congenital patellar syndrome.

    PubMed

    Ezirmik, Naci; Yildiz, Kadri; Can, Cahit Emre

    2012-08-01

    Multiple pterygium syndrome (MPS) is a syndrome that is characterized abnormal face, short length and skin pterygiums on some body legions (servical, antecubital, popliteal, interdigital and on neck). It is also called as Pterygium Colli syndrome, Escobar syndrome or Pterygium syndrome. Escobar (multyple pterygium) syndrome is a rare syndrome. Intrauterin growth reterdation, abnormal face, wide-spead pterygiums that resulted in joint contractures, ptosis, chryptoorchidism, patellar dysplasia and foot deformities are seen on this syndrome. Primarly autosomal resesive crossing are observed; also autosomal dominant and X-linked crossing. This case were presented as it has components of Escobar syndrome and Isolated Patellar Aplasia syndrome in same time.

  2. Assessment for congenital long QT syndrome.

    PubMed

    Heidenreich, Wayne F

    2003-01-01

    A 29-year-old male presented for an evaluation of his risk for having congenital long QT syndrome. Despite being asymptomatic and having a normal QTc interval on the resting ECG, a suggestive family history was an indication for a thorough cardiac evaluation. A geneticist reviewed this workup and recommended against genetic testing. While up to 10% of affected carriers of a congenital long QT syndrome gene mutation can be asymptomatic with a normal QTc, consideration of all of the clinical factors allowed for further risk stratification. The evaluation of an ECG for the long QT syndrome includes calculating a corrected QT interval for the heart rate and assessing the T-waves for morphology associated with this syndrome.

  3. Handicapping Conditions Associated with the Congenital Rubella Syndrome.

    ERIC Educational Resources Information Center

    Vernon, McCay; And Others

    1980-01-01

    The authors discuss the incidence of impairments diagnosed among children with congenital rubella syndrome. Approximately 73 percent are hearing impaired, at least 35 percent have congenital heart disorders, and 33 percent have visual defects. (Author)

  4. Congenital lobar emphysema associated with polysplenia syndrome

    PubMed Central

    Choh, Naseer A.; Choh, Suhil A.; Jehangir, Majid; Naikoo, Bashir A.

    2010-01-01

    Polysplenia, or left isomerism, is a rare heterotaxy syndrome characterized by bilateral bi-lobed lungs, bilateral pulmonary atria, a symmetrical midline liver, and multiple aberrant splenic nodules. We report a case of polysplenia associated with congenital lobar emphysema apart from other typical anomalies. Such an association has not been previously reported. The patient was a young male with progressive exertional breathlessness referred for high resolution CT of the lungs. CT, MRI and echocardiography revealed (in addition to congenital lobar emphysema of right lung) a hemiazygos continuation of the inferior vena cava, a persistent left superior vena cava, multiple splenunculi in the right hypochondrium, midline liver, bilateral bilobed lungs, a large pulmonary artery (suggestive of severe pulmonary artery hypertension) and a large VSD—a typical constellation of findings described in polysplenia syndrome. PMID:20864788

  5. [Synchronous appearance and improvement with anticancer chemotherapy of paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome complicated with small cell lung cancer].

    PubMed

    Koriyama, Haruki; Kyoraku, Itaru; Yamashita, Shuichi; Shiomi, Kazutaka; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2013-01-01

    A 62-year-old man who had suffered from instability of gait and double vision for two months was admitted to our hospital because of weakness of the extremities and ataxia of the extremities and trunk. Chest X-rays and CT scans showed enlargement of the left hilar lymph nodes and a nodular shadow in the left lung. Transbronchial biopsy revealed small cell lung cancer. We diagnosed the patient with two conditions: paraneoplastic cerebellar degeneration (PCD), based on cerebellar ataxia, the presence of Hu antineuronal antibodies, and the absence of cerebellar atrophy and malignancy; and Lambert-Eaton myasthenic syndrome (LEMS), based on weakness of the extremities, the presence of P/Q-type voltage-gated calcium channel antibodies, and waxing in the evoked electromyogram. Anticancer chemoradiation therapy that was started within three months of symptom onset resulted in reductions in size of the hilar lymph nodes and the nodule. Concurrently, cerebellar ataxia, weakness of the extremities, and double vision all disappeared. Anticancer chemotherapy is effective against LEMS while usually less effective against PCD. Early commencement of anticancer chemotherapy is recommended for the treatment of PCD with LEMS.

  6. Congenital Syndromes and Mildly Handicapped Students: Implications for Special Educators.

    ERIC Educational Resources Information Center

    Smith, Sandra M.

    1989-01-01

    Many learning disabilities or cases of mild retardation are due to medically diagnosable, congenital syndromes, such as fetal alcohol syndrome, sex chromosome abnormalities, multiple anomaly syndromes, phenylketonuria, and Tourette Syndrome. These syndromes are discussed, and suggestions are given for special education management. (Author/JDD)

  7. Congenital Melanocytic Nevus Syndrome: A Case Series.

    PubMed

    Recio, A; Sánchez-Moya, A I; Félix, V; Campos, Y

    2017-01-19

    Congenital melanocytic nevus syndrome (CMNS) is the result of an abnormal proliferation of melanocytes in the skin and central nervous system caused by progenitor-cell mutations during embryonic development. Mutations in the NRAS gene have been detected in many of these cells. We present 5 cases of giant congenital melanocytic nevus, 3 of them associated with CMNS; NRAS gene mutation was studied in these 3 patients. Until a few years ago, surgery was the treatment of choice, but the results have proved unsatisfactory because aggressive interventions do not improve cosmetic appearance and only minimally reduce the risk of malignant change. In 2013, trametinib was approved for use in advanced melanoma associated with NRAS mutations. This drug, which acts on the intracellular RAS/RAF/MEK/pERK/MAPK cascade, could be useful in pediatric patients with CMNS. A better understanding of this disease will facilitate the development of new strategies.

  8. [Congenital bone marrow failure syndromes. The last 20 years by the example of congenital neutropenia].

    PubMed

    Zeidler, C; Welte, K

    2007-12-01

    Congenital bone marrow failure syndromes are rare diseases characterised by a reduction of mature blood cells (erythrocytes, platelets, neutrophils). Examples of such disorders include congenital aplastic anemia (Fanconi anemia), congenital hypoplastic anemia (Diamond-Blackfan anemia), congenital neutropenias (Kostmann syndrome, cyclic neutropenia, Shwachman-Diamond syndrome and others), and congenital thrombocytopenias (TAR syndrome, amegacaryocytic thrombocytopenia). In Germany the prevalence of congenital bone marrow failure syndromes can be estimated to be 10/1,000,000 children and adolescents. Although rare, these diseases contributed significantly to the current knowledge on normal haematopoiesis. The documentation of rare diseases by patient registries and the cooperation of clinical centres within networks are most important for the resolution of such disorders. In the following, congenital neutropenia will be presented as an example: Until the 1980s congenital neutropenia could only be classified clinically. Few cases had been reported in the literature. All subtypes were therefore collected under the general term "congenital neutropenia". The establishment of an international network of experts and the long-term documentation of the courses of disease in a common database allowed for statistically workable data in response to therapy, secondary diagnoses and the long-term prognosis. A close cooperation with scientists finally led to the characterisation of genetically different disorders with common pathomechanisms.

  9. Modeling Syndromic Congenital Heart Defects in Zebrafish.

    PubMed

    Grant, Meagan G; Patterson, Victoria L; Grimes, Daniel T; Burdine, Rebecca D

    2017-01-01

    Cardiac development is a dynamic process regulated by spatial and temporal cues that are integrated to effect molecular, cellular, and tissue-level events that form the adult heart. Disruption of these highly orchestrated events can be devastating for cardiac form and function. Aberrations in heart development result in congenital heart defects (CHDs), which affect 1 in 100 infants in the United States each year. Zebrafish have proven informative as a model organism to understand both heart development and the mechanisms associated with CHDs due to the similarities in heart morphogenesis among vertebrates, as well as their genetic tractability and amenability to live imaging. In this review, we discuss the mechanisms of zebrafish heart development and the utility of zebrafish for understanding syndromic CHDs, those cardiac abnormalities that occur in the context of multisystem disorders. We conclude with avenues of zebrafish research that will potentially inform future therapeutic approaches for the treatment of CHDs.

  10. PHACE syndrome and congenitally absent thyroid gland at MR imaging.

    PubMed

    Mamlouk, Mark D; Yu, John-Paul J; Asch, Sarah; Mathes, Erin F

    2016-01-01

    PHACE syndrome is a rare neurocutaneous disorder characterized by posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, and abnormalities of the eye. Thyroid disorders associated with PHACE syndrome have been described, although there are limited reports of this rare occurrence. We report a case of PHACE syndrome with congenital hypothyroidism in an infant, for which absent thyroid gland was diagnosed at magnetic resonance imaging.

  11. Primary congenital glaucoma associated with Patau syndrome with long survival.

    PubMed

    Jaru-Ampornpan, Pimkwan; Kuchtey, John; Dev, V G; Kuchtey, Rachel

    2010-06-23

    Ocular abnormalities are common in Patau syndrome (trisomy 13), but only a few cases with congenital glaucoma have been reported, some of which were associated with other ocular defects. This report describes a case of primary congenital glaucoma in an 11-year-old patient with full trisomy 13.

  12. Autosomal dominant congenital Horner's syndrome in a Dutch family.

    PubMed Central

    Hageman, G; Ippel, P F; te Nijenhuis, F C

    1992-01-01

    A Dutch family is reported with congenital Horner's syndrome in five cases spanning five generations, with symptoms of varying degree but mainly ptosis and meiosis. Heterochromia iridium, anhidrosis, and enophthalmos were not present. The site of the lesion may be in the region between Gasser's ganglion and the short vertical segment of the internal carotid artery near the siphon. There are only four previous reports showing autosomal dominant inheritance of congenital Horner's syndrome. Images PMID:1548493

  13. Autosomal dominant congenital Horner's syndrome in a Dutch family.

    PubMed

    Hageman, G; Ippel, P F; te Nijenhuis, F C

    1992-01-01

    A Dutch family is reported with congenital Horner's syndrome in five cases spanning five generations, with symptoms of varying degree but mainly ptosis and meiosis. Heterochromia iridium, anhidrosis, and enophthalmos were not present. The site of the lesion may be in the region between Gasser's ganglion and the short vertical segment of the internal carotid artery near the siphon. There are only four previous reports showing autosomal dominant inheritance of congenital Horner's syndrome.

  14. Congenital rubella syndrome with autistic disorder.

    PubMed

    Hwang, Shyh-Jou; Chen, Ying-Sheue

    2010-02-01

    Congenital rubella syndrome (CRS) consists of a group of abnormalities that develop in children as a result of maternal infection with rubella virus. CRS may lead to new physical symptoms during adolescence or adulthood, referred to as "late manifestations". Psychiatric disorders are often seen among CRS patients, with an incidence of 4.12-7.3% for autism. We report a case of adolescent CRS with autism. A 20-year-old man had received treatment with antipsychotics and antidepressants since the age of 12 years because of unstable moods, violence, and stereotypic behavior. During follow-up, he developed some insidious-onset physical problems, including hyperlipidemia, dyspnea, constipation, torticollis and a tilted trunk. Under careful survey and evaluation, some physical problems were recognized as side effects of psychotropics, which gradually subsided after adjustment of the medications, and some of the problems were considered partially as manifestations of CRS, such as progressive pulmonary artery stenosis-related dyspnea. We managed some of the patient's physical problems and then he received catheterization for pulmonary artery stenosis. His general physical condition improved and some further improvement in psychiatric status was noted thereafter. Because of a high comorbidity rate for patients with autistic disorder, the clinician should be aware of the possibility of CRS if the patient has multiple congenital physical abnormalities with a history of maternal rubella infection. If patients develop physical symptoms in adolescence, awareness of late manifestations of CRS and differentiation from the adverse effects of psychotropic medications are essential. In addition to psychiatric treatment, management of physical problems associated with CRS would be beneficial for the patients' psychiatric condition.

  15. Baller-Gerold syndrome associated with congenital portal venous malformation.

    PubMed Central

    Savarirayan, R; Tomlinson, P; Thompson, E

    1998-01-01

    We report a 4 year old boy in whom the clinical features of craniosynostosis and bilateral absent radii led to a diagnosis of Baller-Gerold syndrome. Additional congenital abnormalities included midface hypoplasia, atrial and ventricular septal defects, right hydronephrosis, partial sacral agenesis, and anterior ectopic anus. Evidence of portal venous hypertension was present from 8 months and a congenital portal venous malformation was discovered at 2 years. This is the first reported case of Baller-Gerold syndrome associated with a congenital portal venous malformation. We discuss the diagnostic confusion between this syndrome and other overlapping malformation syndromes and propose optimal evaluation strategies aimed at clarifying the nosology of these syndromes. Images PMID:9733037

  16. Arrhythmic risk in congenital long QT syndrome.

    PubMed

    Kaufman, Elizabeth S

    2011-01-01

    One of the most important and challenging aspects of caring for patients with congenital long QT syndrome (LQTS) is assessing an individual's risk of sudden cardiac death (SCD) because of torsades de pointes. Current risk assessment integrates clinical and genetic features known to be associated with SCD, but more accurate methods of risk assessment could lead to more appropriate use of therapies, potentially saving lives and avoiding overtreatment. Conventional indices of risk include sex, age, extent of QT prolongation, history of symptoms (syncope or aborted SCD), and genetic subtype. The biophysical properties of specific mutations (eg, those that affect transmembrane segments of the ion channel protein or those that cause a dominant negative effect on ion channel function vs haplotype insufficiency) also contribute to risk. A growing body of basic mechanistic and clinical evidence points to heterogeneity of repolarization as a potent determinant of risk in LQTS patients. Mechanistically, heterogeneities of repolarization provide substrate for reentry, which likely causes perpetuation of torsades de pointes. Clinical markers that reflect heterogeneity of repolarization include abnormal microvolt-level T wave alternans, increased Tpeak-end interval, and dispersion of mechanical contraction time. The optimal methodology for using these indices as risk predictors in LQTS remains under active investigation. Further studies are needed to determine how indices of heterogeneity such as microvolt-level T wave alternans, Tpeak-end interval, and dispersion of mechanical contraction can be incorporated into models of risk prediction in LQTS, both for initial risk stratification and for assessment of efficacy of therapies.

  17. Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect.

    PubMed

    Guo, Yiran; Menezes, Minal J; Menezes, Manoj P; Liang, Jinlong; Li, Dong; Riley, Lisa G; Clarke, Nigel F; Andrews, P Ian; Tian, Lifeng; Webster, Richard; Wang, Fengxiang; Liu, Xuanzhu; Shen, Yulan; Thorburn, David R; Keating, Brendan J; Engel, Andrew; Hakonarson, Hakon; Christodoulou, John; Xu, Xun

    2015-03-01

    Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes.

  18. Lambert-Eaton Myasthenic Syndrome

    MedlinePlus

    ... Association National Office - 222 S. Riverside Plaza Suite 1500 Chicago IL Chicago, IL 60606 mda@mdausa.org http://www.mda. ... Association National Office - 222 S. Riverside Plaza Suite 1500 Chicago IL Chicago, IL 60606 mda@mdausa.org http:// ...

  19. Bilateral congenital cataracts in an infant with Klinefelter syndrome.

    PubMed

    Nur, Banu Güzel; Altıok-Clark, Özden; İlhan, Hatice Deniz; Sayar, Ersin; Yücel, İclal; Mıhçı, Ercan

    2014-01-01

    Congenital cataract is one of the most treatable causes of visual impairment and blindness during infancy, with an estimated prevalence of approximately 2.5:10,000 infants under the age of 1 year. Congenital cataract can be observed with certain chromosomal abnormalities, such as trisomies, deletions, translocations and Turner syndrome. In Klinefelter syndrome, however, ocular complications and cataract are not commonly encountered, so reports in the literature are very rare. In this manuscript, we present a 3-month-old male infant who had congenital cataracts. Chromosomal analysis revealed that his karyotype was 47,XXY. He did not show any of the main clinical signs of Klinefelter syndrome because of his very young age. To the best of our knowledge, our patient is only the second-ever case reported in the literature in which congenital cataracts have been found in an infant with a nonmosaic 47,XXY karyotype. The aim of the present report is to both describe the ocular abnormalities that can sometimes be found in Klinefelter syndrome and to emphasize the importance of performing a karyotype analysis in order to rule out chromosome abnormalities in patients with congenital cataracts.

  20. Congenital upper eyelids ectropion in Down’s syndrome

    PubMed Central

    Corredor-Osorio, Rafael; Tovilla-Pomar, José Luis; Tovilla-Canales, José Luis

    2017-01-01

    Congenital bilateral ectropion of the upper eyelids is a rare, benign condition reported in ophthalmic literature. It is more frequently associated with Down’s syndrome, ichthyosis, and sporadic cases in newborns from black population. We report three cases of congenital bilateral upper eyelid ectropion associated with Down’s syndrome. Management of these patients usually requires medial and lateral canthoplasties, full-thickness pentagonal resection of the upper eyelids and placement of skin grafts. We present herein the evolution of one of these patients and we will discuss the mechanism of the eyelid ectropion and its treatment. PMID:28194320

  1. Diaphragm pacers as a treatment for congenital central hypoventilation syndrome.

    PubMed

    Chen, Maida Lynn; Tablizo, Mary Anne; Kun, Sheila; Keens, Thomas G

    2005-09-01

    Congenital central hypoventilation syndrome is a rare syndrome present from birth, and is defined as the failure of automatic control of breathing. All patients with congenital central hypoventilation syndrome require life-long ventilatory support during sleep, although approximately a third of patients require ventilatory support 24 h per day. Diaphragm pacers offer a modality of ventilatory support that affords congenital central hypoventilation syndrome patients with maximal mobility for full-time ventilatory patients, and they may allow for a more normal lifestyle in the appropriate patient. They may permit tracheostomy decannulation in those requiring only support during sleep. Diaphragm pacing entails surgical placement of an electrode onto the phrenic nerve, connected to a subcutaneous receiver. There is an external battery-operated transmitter and antenna placed on the skin over the receiver. The transmitter emits energy, similar to radio transmission, which is converted into an electrical current by the receiver. This stimulates the phrenic nerve resulting in a diaphragmatic contraction. Settings on the transmitter include respiratory rate and electrical voltage, and are adjusted to give enough tidal volume to allow for adequate oxygenation and ventilation. Therefore, diaphragm pacing is an attractive alternative mode of mechanically assisted ventilation for many patients with congenital central hypoventilation syndrome.

  2. Congenital High Airway Obstruction Syndrome (CHAOS) as part of Fraser syndrome: ultrasound and autopsy findings.

    PubMed

    Mesens, T; Witters, I; Van Robaeys, J; Peeters, H; Fryns, J P

    2013-01-01

    Congenital High Airway Obstruction Syndrome (CHAOS) is a potential lethal condition. We describe a case report of CHAOS, with additional malformations diagnosed at 20 weeks. Autopsy findings are suggestive for Fraser syndrome (cryptophthalmos-syndactyly syndrome; OMIM 219000). The diagnosis was confirmed by mutation analysis of FRAS1.

  3. Congenital horner syndrome and hemiplegia secondary to carotid dissection.

    PubMed

    Gupta, Mohit; Dinakaran, Subramanian; Chan, Tan K

    2005-01-01

    A 5-month-old infant had right Horner syndrome and left hemiplegia. Magnetic resonance imaging confirmed smaller cerebral hemisphere and magnetic resonance angiography showed reduced blood flow in the internal carotid artery on the right. A diagnosis of congenital hemiplegia and carotid occlusion secondary to maternal trauma during pregnancy was made.

  4. Associated congenital anomalies among cases with Down syndrome.

    PubMed

    Stoll, Claude; Dott, Beatrice; Alembik, Yves; Roth, Marie-Paule

    2015-12-01

    Down syndrome (DS) is the most common congenital anomaly widely studied for at least 150 years. However, the type and the frequency of congenital anomalies associated with DS are still controversial. Despite prenatal diagnosis and elective termination of pregnancy for fetal anomalies, in Europe, from 2008 to 2012 the live birth prevalence of DS per 10,000 was 10. 2. The objectives of this study were to examine the major congenital anomalies occurring in infants and fetuses with Down syndrome. The material for this study came from 402,532 consecutive pregnancies of known outcome registered by our registry of congenital anomalies between 1979 and 2008. Four hundred sixty seven (64%) out of the 728 cases with DS registered had at least one major associated congenital anomaly. The most common associated anomalies were cardiac anomalies, 323 cases (44%), followed by digestive system anomalies, 42 cases (6%), musculoskeletal system anomalies, 35 cases (5%), urinary system anomalies, 28 cases (4%), respiratory system anomalies, 13 cases (2%), and other system anomalies, 26 cases (3.6%). Among the cases with DS with congenital heart defects, the most common cardiac anomaly was atrioventricular septal defect (30%) followed by atrial septum defect (25%), ventricular septal defect (22%), patent ductus arteriosus (5%), coarctation of aorta (5%), and tetralogy of Fallot (3%). Among the cases with DS with a digestive system anomaly recorded, duodenal atresia (67%), Hirschsprung disease (14%), and tracheo-esophageal atresia (10%) were the most common. Fourteen (2%) of the cases with DS had an obstructive anomaly of the renal pelvis, including hydronephrosis. The other most common anomalies associated with cases with DS were syndactyly, club foot, polydactyly, limb reduction, cataract, hydrocephaly, cleft palate, hypospadias and diaphragmatic hernia. Many studies to assess the anomalies associated with DS have reported various results. There is no agreement in the literature as to

  5. Nitric oxide-sensitive pulmonary hypertension in congenital rubella syndrome.

    PubMed

    Raimondi, Francesco; Migliaro, Fiorella; Di Pietro, Elisa; Borgia, Francesco; Rapacciuolo, Antonio; Capasso, Letizia

    2015-01-01

    Persistent pulmonary hypertension is a very rare presentation of congenital virus infection. We discuss the case of complete congenital rubella syndrome presenting at echocardiography with pulmonary hypertension that worsened after ductus ligation. Cardiac catheterization showed a normal pulmonary valve and vascular tree but a PAP = 40 mmHg. The infant promptly responded to inhaled nitric oxide while on mechanical ventilation and was later shifted to oral sildenafil. It is not clear whether our observation may be due to direct viral damage to the endothelium or to the rubella virus increasing the vascular tone via a metabolic derangement.

  6. The phenotypic spectrum of congenital Zika syndrome.

    PubMed

    Del Campo, Miguel; Feitosa, Ian M L; Ribeiro, Erlane M; Horovitz, Dafne D G; Pessoa, André L S; França, Giovanny V A; García-Alix, Alfredo; Doriqui, Maria J R; Wanderley, Hector Y C; Sanseverino, Maria V T; Neri, João I C F; Pina-Neto, João M; Santos, Emerson S; Verçosa, Islane; Cernach, Mirlene C S P; Medeiros, Paula F V; Kerbage, Saile C; Silva, André A; van der Linden, Vanessa; Martelli, Celina M T; Cordeiro, Marli T; Dhalia, Rafael; Vianna, Fernanda S L; Victora, Cesar G; Cavalcanti, Denise P; Schuler-Faccini, Lavinia

    2017-04-01

    In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.

  7. Congenital complete heart block in Klippel-Feil syndrome.

    PubMed

    Elumalai, Raja Saravanan; Nainar, Madhu Sankar; Vaidyanathan, Kirthivasan; Somasundaram, Ganesh; Balasubramaniam, Govini

    2013-04-01

    A 36-year-old man with a short neck, low hairline, and mild kyphoscoliosis, presented with history of syncope. Chest radiography revealed a diaphragmatic hernia. Computed tomography demonstrated fusion of C2-C6 vertebral bodies, Electrocardiography indicated complete heart block. Ultrasonography showed a right pelvic kidney. He was diagnosed with Klippel-Feil syndrome and underwent permanent pacemaker implantation and corrective surgery for the congenital diaphragmatic hernia.

  8. Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome.

    PubMed

    Seaver, L H; Joffe, L; Spark, R P; Smith, B L; Hoyme, H E

    1993-04-15

    An apparently autosomal recessive syndrome of hereditary vitreoretinal degeneration (VRD) with retinal detachment, high myopia, and congenital encephalocele was described in 1971 by Knobloch and Layer [J Pediatr Ophthalmol 8:181-184]. Clinical confirmation of the presence of encephaloceles was lacking, and no neuropathologic studies were reported. We have evaluated a similarly affected family with 2 sibs with high myopia, VRD, and occipital scalp defects. Histologic examination of the scalp defects showed heterotopic neuronal tissue in both instances. The older girl has had a unilateral retinal detachment. Her other eye and both eyes of the younger sib have so far been treated successfully with prophylactic retinal cryotherapy. Both children have normal to above normal intelligence. The family reported by Knobloch and Layer [1971] and the sibship herein described appear to represent a distinct autosomal recessive trait. Analysis of the associated defects suggests an underlying defect in early cephalic neuroectodermal morphogenesis. Data from these families imply that congenital occipital scalp defects rather than true encephaloceles may, as is true in some cases of Meckel syndrome, accompany Knobloch syndrome. The presence of a congenital midline scalp defect should alert the clinician to possible underlying central nervous system and/or ocular pathology and should lead to consideration of further diagnostic evaluations and prophylactic measures.

  9. Genitourinary anomaly in congenital varicella syndrome: case report and review.

    PubMed

    Fujita, Hisayo; Yoshii, Akira; Maeda, Jun; Kosaki, Kenjiro; Shishido, Seiichiro; Nakai, Hideo; Awazu, Midori

    2004-05-01

    We describe a 1-year-old boy with congenital varicella syndrome who had vesicoureteral reflux (VUR) and neurogenic bladder. His mother had varicella during the 3rd month of pregnancy. At birth the patient presented with right microphthalmia, right microcornea, and persistent hyperplastic primary vitreous of the right eye. He had chronic constipation from 3 months of age. He had urinary tract infection at 1 year of age. Urological investigation revealed left grade V VUR and neurogenic bladder. His varicella zoster virus IgG titer measured by ELISA was 39.4 antibody index (normal <0.1). He had repeated episodes of urinary tract infection despite antibiotic prophylaxis and clean intermittent catheterization, and underwent a uretero-vesiconeostomy at 2 years of age. Maternal infection during early pregnancy and the serological evidence of varicella zoster IgG antibodies without a history of varicella after birth led to the diagnosis of congenital varicella syndrome. Urogenital anomalies have previously been described in 14 cases of congenital varicella syndrome. Most of these patients had neurogenic bladder, the pathophysiology of which could be explained by the known neurotropic nature of the virus.

  10. Human congenital long QT syndrome: more than previously thought?

    PubMed

    Attali, Bernard

    2002-06-01

    Mutations in KCNQ1 and KCNE1, the alpha- and beta-subunits of the I(KS) K+ channel, produce the cardiac long QT (LQT) syndrome. These subunits are expressed in heart and inner ear, but also in epithelial tissues such as kidney or intestine where their functional roles have remained elusive. Recent work has shown that KCNE1-deficient mice display chronic hypokalemia and hyperaldosteronism. These results have significant implications for human congenital LQT syndromes because hypokalemia increases the risk of ventricular arrhythmia and cardiac sudden death.

  11. Treatment of steroid-resistant post-transplant nephrotic syndrome with cyclophosphamide in a child with congenital nephrotic syndrome.

    PubMed

    Flynn, J T; Schulman, S L; deChadarevian, J P; Dunn, S P; Kaiser, B A; Polinsky, M S; Baluarte, H J

    1992-11-01

    A child with congenital nephrotic syndrome underwent renal transplantation, was treated for acute rejection, and then developed nephrotic syndrome and renal failure. He was felt to have minimal change disease on allograft biopsy, but failed to respond to therapy with corticosteroids. Cyclophosphamide was substituted for cyclosporine and rapidly induced a complete remission of his nephrotic syndrome. We feel that this case not only represents an important example of a useful therapeutic approach to the child with congenital nephrotic syndrome who develops nephrotic syndrome post transplantation, and also raises questions concerning the pathogenesis of congenital nephrotic syndrome.

  12. Genetic and clinical advances in congenital long QT syndrome.

    PubMed

    Mizusawa, Yuka; Horie, Minoru; Wilde, Arthur A M

    2014-01-01

    Congenital long QT syndrome (LQTS) is an inherited arrhythmia syndrome characterized by a prolonged QT interval on the 12-lead ECG, torsades de pointes and a higher chance of sudden cardiac death. LQTS segregates in a Mendelian fashion, which includes Romano-Ward syndrome with an autosomal dominant pattern as well as a rare autosomal recessive pattern (Jervell and Lange-Nielsen syndrome). Since 1957 when Jervell and Lange-Nielsen reported the first familial LQTS with congenital deafness, progress in understanding the genetic and electrophysiological mechanisms of LQTS has tremendously improved diagnostic methods and treatments. In the meantime, it has become evident that LQTS may not always be explained by a single gene mutation, but seems to follow a more complex genetic model intertwined with genetic common polymorphisms that have a mild to moderate effect on disease expression. In this review, we summarize the characteristics of LQTS (mainly LQT1-3) and briefly describe the most recent advances in LQTS clinical diagnostics as well as genetics.

  13. Mounier-Kuhn syndrome or congenital tracheobronchomegaly: a literature review.

    PubMed

    Krustins, Eduards; Kravale, Zaiga; Buls, Atis

    2013-12-01

    Mounier-Kuhn syndrome or congenital tracheobronchomegaly is a chronic airway condition which for currently unknown reasons mostly affects males. It is commonly overlooked on conventional chest X-rays, and is considered to be rare, but the prevalence might be higher as commonly assumed. The hallmark of it is a dilatation of the main airways which frequently, but not always, causes marked, mainly respiratory, symptoms, and patients usually present with varying degrees of recurrent infections, breathlessness, haemoptysis, dyspnoea. Although at least 200 case reports have been published, there have been only a few attempts to review them, and none in the last 20 years. Due to the lack of clinical trials and wide variability of case-report format, a systematic review was deemed not feasible, therefore PubMed and Medline databases were searched using terms "Mounier-Kuhn syndrome", "tracheobronchomegaly", "tracheomegaly", and "bronchomegaly", without any time restrictions, to summarize currently known facts about the syndrome. To the authors' best knowledge, the result is currently the most comprehensive review of previously published literature about the congenital tracheobronchomegaly, and summarizes what's known about symptoms, prevalence, disease associations, and treatment options for this syndrome.

  14. [Pulmonary hypertension associated with congenital heart disease and Eisenmenger syndrome].

    PubMed

    Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel

    2015-01-01

    Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy.

  15. Congenital rubella syndrome in child of woman without known risk factors, New Jersey, USA.

    PubMed

    Pitts, Samantha I; Wallace, Gregory S; Montana, Barbara; Handschur, Elizabeth F; Meislich, Debrah; Sampson, Alethia C; Canuso, Suzanne; Horner, Jennifer; Barskey, Albert E; Abernathy, Emily S; Icenogle, Joseph P

    2014-02-01

    We report a case of congenital rubella syndrome in a child born to a vaccinated New Jersey woman who had not traveled internationally. Although rubella and congenital rubella syndrome have been eliminated from the United States, clinicians should remain vigilant and immediately notify public health authorities when either is suspected.

  16. Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome).

    PubMed

    Desir, Julie; Abramowicz, Marc

    2008-10-15

    Harboyan syndrome is a degenerative corneal disorder defined as congenital hereditary endothelial dystrophy (CHED) accompanied by progressive, postlingual sensorineural hearing loss. To date, 24 cases from 11 families of various origin (Asian Indian, South American Indian, Sephardi Jewish, Brazilian Portuguese, Dutch, Gypsy, Moroccan, Dominican) have been reported. More than 50% of the reported cases have been associated with parental consanguinity. The ocular manifestations in Harboyan syndrome include diffuse bilateral corneal edema occurring with severe corneal clouding, blurred vision, visual loss and nystagmus. They are apparent at birth or within the neonatal period and are indistinguishable from those characteristic of the autosomal recessive CHED (CHED2). Hearing deficit in Harboyan is slowly progressive and typically found in patients 10-25 years old. There are no reported cases with prelinglual deafness, however, a significant hearing loss in children as young as 4 years old has been detected by audiometry, suggesting that hearing may be affected earlier, even at birth. Harboyan syndrome is caused by mutations in the SLC4A11 gene located at the CHED2 locus on chromosome 20p13-p12, indicating that CHED2 and Harboyan syndrome are allelic disorders. A total of 62 different SLC4A11 mutations have been reported in 98 families (92 CHED2 and 6 Harboyan). All reported cases have been consistent with autosomal recessive transmission. Diagnosis is based on clinical criteria, detailed ophthalmological assessment and audiometry. A molecular confirmation of the clinical diagnosis is feasible. A variety of genetic, metabolic, developmental and acquired diseases presenting with clouding of the cornea should be considered in the differential diagnosis (Peters anomaly, sclerocornea, limbal dermoids, congenital glaucoma). Audiometry must be performed to differentiate Harboyan syndrome from CHED2. Autosomal recessive types of CHED (CHED2 and Harboyan syndrome) should

  17. Congenital Mirror Movements in Gorlin Syndrome: A Case Report With DTI and Functional MRI Features.

    PubMed

    Sag, Erdal; Gocmen, Rahsan; Yildiz, F Gokcem; Ozturk, Zeynelabidin; Temucin, Cagri; Teksam, Ozlem; Utine, Eda

    2016-03-01

    Congenital mirror movements are rare conditions that define the inability to perform unimanual movements. Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a genetic disorder with multiple nevi predisposing to basal cell carcinoma, odontogenic keratocysts, and skeletal malformations. Herein we report on an adolescent patient with Gorlin syndrome and coexisting congenital mirror movements. To our knowledge, this is the first patient in the literature who has both of these very rare conditions.

  18. Congenital Zika syndrome with arthrogryposis: retrospective case series study

    PubMed Central

    Filho, Epitacio Leite Rolim; Lins, Otavio Gomes; Aragão, Maria de Fátima Viana Vasco; Brainer-Lima, Alessandra Mertens; Cruz, Danielle Di Cavalcanti Sousa; Rocha, Maria Angela Wanderley; Sobral da Silva, Paula Fabiana; Carvalho, Maria Durce Costa Gomes; do Amaral, Fernando José; Gomes, Joelma Arruda; Ribeiro de Medeiros, Igor Colaço; Ventura, Camila V; Ramos, Regina Coeli

    2016-01-01

    Objective To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. Design Retrospective case series study. Setting Association for Assistance of Disabled Children, Pernambuco state, Brazil. Participants Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. Results The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. Conclusions Congenital Zika syndrome should be added to the differential diagnosis of congenital

  19. Severe congenital thrombocytopaenia--first clinical manifestation of Noonan syndrome.

    PubMed

    Nunes, Paula; Aguilar, Sara; Prado, Sara Noéme; Palaré, Maria João; Ferrão, Anabela; Morais, Anabela

    2012-03-20

    This report focuses on a male infant, the first born of non-consanguineous parents diagnosed with polyhydramnios at 26 weeks of gestation. The newborn was admitted during the neonatal period with bleeding diathesis associated with a low platelet count at birth (5×10(9)/l).The authors registered a persistent low platelet count (9000-129 000/l) during the infants 1st year of life. Physical examination revealed a petechial rash, a dysmorphic face and bilateral cryptorchidism, in the absence of organomegaly. Additionally, cardiologic evaluation revealed an aortic valve dysplasia and an atrial septal defect, while bone marrow biopsy and aspiration were found normal. Throughout the investigation, the authors excluded congenital infection, alloimmune and familiar thrombocytopaenia, Fanconi anaemia and thrombocytopaenia absent radius syndrome. The cytogenetic analysis revealed a mutation in the PTPN11 gene associated with Noonan syndrome. Here the author highlights that severe neonatal thrombocytopaenia is a manifestation that should be considered in the diagnosis and clinical management of Noonan's syndrome.

  20. Severe congenital thrombocytopaenia – first clinical manifestation of Noonan syndrome

    PubMed Central

    Nunes, Paula; Aguilar, Sara; Prado, Sara Noéme; Palaré, Maria João; Ferrão, Anabela; Morais, Anabela

    2012-01-01

    This report focuses on a male infant, the first born of non-consanguineous parents diagnosed with polyhydramnios at 26 weeks of gestation. The newborn was admitted during the neonatal period with bleeding diathesis associated with a low platelet count at birth (5×109/l).The authors registered a persistent low platelet count (9000–129 000/l) during the infants 1st year of life. Physical examination revealed a petechial rash, a dysmorphic face and bilateral cryptorchidism, in the absence of organomegaly. Additionally, cardiologic evaluation revealed an aortic valve dysplasia and an atrial septal defect, while bone marrow biopsy and aspiration were found normal. Throughout the investigation, the authors excluded congenital infection, alloimmune and familiar thrombocytopaenia, Fanconi anaemia and thrombocytopaenia absent radius syndrome. The cytogenetic analysis revealed a mutation in the PTPN11 gene associated with Noonan syndrome. Here the author highlights that severe neonatal thrombocytopaenia is a manifestation that should be considered in the diagnosis and clinical management of Noonan’s syndrome. PMID:22605701

  1. Congenital Auricular Malformations: Description of Anomalies and Syndromes.

    PubMed

    Bartel-Friedrich, Sylva

    2015-12-01

    Half of the malformations in the ear, nose, and throat region affect the ear. Malformations of the external ear (pinna or auricle with external auditory canal [EAC]) are collectively termed microtia. Microtia is a congenital anomaly that ranges in severity from mild structural abnormalities to complete absence of the external ear (anotia). Microtia occurs more frequently in males (∼2 or 3:1), is predominantly unilateral (∼70-90%), and more often involves the right ear (∼60%). The reported prevalence varies geographically from 0.83 to 17.4 per 10,000 births. Microtia may be genetic (with family history, spontaneous mutations) or acquired. Malformations of the external ear can also involve the middle ear and/or inner ear. Microtia may be an isolated birth defect, but associated anomalies or syndromes are described in 20 to 60% of cases, depending on study design. These generally fit within the oculo-auriculo-vertebral spectrum; defects are located most frequently in the facial skeleton, facial soft tissues, heart, and vertebral column, or comprise a syndrome (e.g., Treacher Collins syndrome). Diagnostic investigation of microtia includes clinical examination, audiologic testing, genetic analysis and, especially in higher grade malformations with EAC deformities, computed tomography (CT) or cone-beam CT for the planning of surgery and rehabilitation procedures, including implantation of hearing aids.

  2. Cortical thickness in a case of congenital unilateral perisylvian syndrome.

    PubMed

    Kotini, A; Camposano, S; Hara, K; Salat, D; Cole, A; Stufflebeam, S; Halgren, E

    2004-11-30

    In congenital perisylvian syndrome, there is polymicrogyric cortex distributed in variable extensions around the sylvian fissure. Unilateral cases usually present with congenital hemiparesis, while bilateral cases have pseudobulbar paralysis of the oropharingoglossal region. Both unilateral and bilateral cases have a high rate of epilepsy. Polymicrogyric cortex is characterized by too many small convolutions. Often there are no intervening sulci, and almost no white matter can be seen under them. On MRI they appear to have increased thickness. Bilateral and symmetric polimycrogiria can be hard to recognize on standard MRIs. Accurate and automated methods for measuring the thickness of cerebral cortex are available. They have mainly been used to study a variety of disorders with diminished cortical thickness. We studied a case of right perisylvian polymicrogyria, who presented in adult life with epilepsy and had a normal neurological exam. Fischl and Dale's automated cortical thickness analysis rendered a very clear picture of increased cortical thickness with values up to 9 mm in the affected areas (normal cortical thickness varies between 1 and 4.5 mm). The thickest areas were seen over grossly abnormal gyri on the reconstructed cerebral cortex. On MEG he presented a prominent and monotonous 9 Hz activity that was located within the limits of a thick gyrus. There was a significant difference of thickness between homologous hemispheric areas. To our surprise some areas of the left hemisphere also appeared to have increased thickness, raising the question of a bilateral asymmetric case.

  3. Craniorachischisis Totalis with Congenital Diaphragmatic Hernia-A Rare Presentation of Fryns Syndrome.

    PubMed

    Singh, Aneet; Pilli, Ganga S; Bannur, Hema

    2016-01-01

    Fryns syndrome is a multiple congenital anomaly syndrome with an autosomal recessive inheritance. Here we describe the autopsy case findings of a 19-week male fetus, born out of a consanguineous marriage. The dissection revealed left-sided diaphragmatic hernia, resulting in pulmonary hypoplasia and shift of heart to the right side. In addition, anencephaly and spina bifida throughout the vertebral column were observed. All six criteria for Fryns syndrome were met. Such a presentation of Fryns syndrome associated with Craniorachischisis Totalis has not been reported so far. We have also tabulated the overlapping features of some multiple congenital anomaly syndromes that need to be distinguished at autopsy for an accurate diagnosis.

  4. Recurrent Congenital Diaphragmatic Hernia in Ehlers-Danlos Syndrome

    SciTech Connect

    Lin, I.C.; Ko, S.F.; Shieh, C.S.; Huang, C.F.; Chien, S.J.; Liang, C.D.

    2006-10-15

    Ehlers-Danlos syndrome (EDS) includes a group of connective tissue disorders with abnormal collagen metabolism and a diverse clinical spectrum. We report two siblings with EDS who both presented with congenital diaphragmatic hernia (CDH). The elder sister suffered from recurrent diaphragmatic hernia twice and EDS was overlooked initially. Echocardiography as well as contrast-enhanced magnetic resonance angiography (MRA) showed dilatation of the pulmonary artery, and marked elongation and tortuosity of the aorta and its branches. A diagnosis of EDS was eventually established when these findings were coupled with the clinical features of hyperelastic skin. Her younger brother also had similar features. This report emphasizes that EDS may present as CDH in a small child which could easily be overlooked. Without appropriate surgery, diaphragmatic hernia might occur. Echocardiographic screening is recommended in patients with CDH. Contrast-enhanced MRA can be helpful in delineation of abnormally tortuous aortic great vessels that are an important clue to the early diagnosis of EDS.

  5. Congenital Deafness with Cardiac Arrhythmias: The Jervell and Lange-Nielsen Syndrome.

    ERIC Educational Resources Information Center

    Wahl, Richard A.; Macdonald, Dick, II

    1980-01-01

    The Jervell and Lange-Nielsen syndrome, affecting 0.3 percent of congenitally deaf persons, consists of severe cardiac arrhythmias and sensorineural hearing loss. The authors recommend that every congenitally deaf child with suspicious symptoms receive an electrocardiogram and that professionals who work with deaf children not only inform…

  6. Association of misoprostol, Moebius syndrome and congenital central alveolar hypoventilation. Case report.

    PubMed

    Nunes, M L; Friedrich, M A; Loch, L F

    1999-03-01

    We report a case showing the association of Moebius syndrome, the use of misoprostol during pregnancy and the development of central congenital alveolar hypoventilation. Pathophysiological aspects of these three diseases are discussed and also the unfavorable prognosis of this association.

  7. Overview of Usher's Syndrome: Congenital Deafness and Progressive Loss of Vision

    ERIC Educational Resources Information Center

    Vernon, McCay

    1974-01-01

    Usher's syndrome, a genetic condition causing congenital profound hearing loss and a progressive blindness due to retinitis pigmentosa, affects an estimated three to six percent of children in educational and rehabilitative programs for the hearing impaired. (Author)

  8. Poorly Controlled Congenital Hypothyroidism due to an Underlying Allgrove Syndrome

    PubMed Central

    van Tellingen, V.; Finken, M.J.J.; Israëls, J.; Hendriks, Y.M.C.; Kamp, G.A.; van Santen, H.M.

    2016-01-01

    Background Congenital hypothyroidism of thyroidal origin (CHT) is a common disorder in pediatric endocrinology practices, which can be difficult to manage. Elevated thyrotropin (TSH) concentrations are in the great majority of cases explained by poor compliance to levothyroxine therapy. Methods Case description. Results We present a boy with CHT, with 2 heterozygous mutations in the TSH receptor gene, who showed persistently elevated TSH concentrations and psychomotor retardation, initially misinterpreted as malcompliance. At the age of 4 years, he was diagnosed with adrenal insufficiency, wherefore a broad diagnostic search was initiated. After the start of glucocorticoid replacement therapy, his TSH normalized and the levothyroxine could be lowered. At the age of 6 years, his TSH increased again, this time caused by malabsorption of levothyroxine due to esophageal achalasia. In retrospect, alacrima was also present and the diagnosis of Allgrove syndrome was genetically confirmed. The CHT was considered a separate disease entity. Conclusions In case of persistently elevated TSH levels in children with CHT, causes other than noncompliance must be considered. Second, in establishing the cause of adrenal insufficiency, specific symptoms, such as alacrima, are easily overlooked. Third, Allgrove syndrome is a rare disorder, in which diagnostic delay can lead to potentially life-threatening complications. PMID:27255745

  9. Nonclassic congenital adrenal hyperplasia misdiagnosed as Turner syndrome.

    PubMed

    Mishra, Vineet V; Pritti, Kumari; Aggarwal, Rohina; Choudhary, Sumesh

    2015-01-01

    We present a patient with nonclassic congenital adrenal hyperplasia (NCAH) misdiagnosed as mosaic Turner syndrome. She presented with complaints of primary infertility. Short stature, the presence of facial hair and hoarse voice was also noted. She had primary amenorrhea and was advised for karyotype at 16 years of age, which was reported as 45, X[20]/46, XX[80], stating her as a case of mosaic Turner syndrome. Clitoroplasty was done at 21 years of age for clitoromegaly, which was noticed during puberty. The diagnosis of mosaic Turner could not explain the virilization. Therefore, we repeated the karyotype, which revealed 46, XX in more than 100 metaphases and was sufficient to exclude mosaicism. Furthermore, the endocrinological evaluation revealed high testosterone level with a normal 17 alpha-hydroxyprogesterone (17-OHP). The presence of pubertal onset virilization with a karyotype of 46, XX and raised testosterone level with normal 17-OHP level, raised the suspicion of NCAH for which adrenocorticotropic hormone stimulation test was done which confirmed the diagnosis of NCAH.

  10. Nonclassic congenital adrenal hyperplasia misdiagnosed as Turner syndrome

    PubMed Central

    Mishra, Vineet V.; Pritti, Kumari; Aggarwal, Rohina; Choudhary, Sumesh

    2015-01-01

    We present a patient with nonclassic congenital adrenal hyperplasia (NCAH) misdiagnosed as mosaic Turner syndrome. She presented with complaints of primary infertility. Short stature, the presence of facial hair and hoarse voice was also noted. She had primary amenorrhea and was advised for karyotype at 16 years of age, which was reported as 45, X[20]/46, XX[80], stating her as a case of mosaic Turner syndrome. Clitoroplasty was done at 21 years of age for clitoromegaly, which was noticed during puberty. The diagnosis of mosaic Turner could not explain the virilization. Therefore, we repeated the karyotype, which revealed 46, XX in more than 100 metaphases and was sufficient to exclude mosaicism. Furthermore, the endocrinological evaluation revealed high testosterone level with a normal 17 alpha-hydroxyprogesterone (17-OHP). The presence of pubertal onset virilization with a karyotype of 46, XX and raised testosterone level with normal 17-OHP level, raised the suspicion of NCAH for which adrenocorticotropic hormone stimulation test was done which confirmed the diagnosis of NCAH. PMID:26751945

  11. Congenital heart defects in two siblings in an Axenfeld-Rieger syndrome family.

    PubMed

    Akkus, Mehmet Necdet; Argin, Atilla

    2010-04-01

    Axenfeld-Rieger syndrome is a genetically heterogeneous, autosomal dominant disorder characterized by anomalies of the anterior segment of the eye, face, teeth, and umbilicus. Many other extraocular findings, including congenital heart defects, have been reported in association with this syndrome. It has been suggested by some investigators that the coexistence of Axenfeld-Rieger syndrome and congenital heart defects is not a chance event but it represents a distinct entity. We report a family in which four members in three generations have typical ocular features of Axenfeld-Rieger syndrome. Two of them, who are siblings, also have congenital heart defects. The congenital heart defect was bicuspid aortic valve anomaly with severe stenosis and mild regurgitation in one sibling and ostium secundum atrial septal defect in the other. To our knowledge, the combination of congenital heart defects with Axenfeld-Rieger syndrome in siblings has not been reported previously. Our observation further strengthens the notion that Axenfeld-Rieger syndrome associated with congenital heart defects is not a chance event.

  12. Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

    PubMed

    Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R

    2015-11-01

    Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations.

  13. 14q12 Microdeletion syndrome and congenital variant of Rett syndrome.

    PubMed

    Mencarelli, Maria Antonietta; Kleefstra, Tjitske; Katzaki, Eleni; Papa, Filomena Tiziana; Cohen, Monika; Pfundt, Rolph; Ariani, Francesca; Meloni, Ilaria; Mari, Francesca; Renieri, Alessandra

    2009-01-01

    Only two patients with 14q12 deletion have been reported to date. Here, we describe an additional patient with a similar deletion in order to improve the clinical delineation of this new microdeletion syndrome. The emerging phenotype is characterized by a Rett-like clinical course with an almost normal development during the first months of life followed by a period of regression. A peculiar facial phenotype is also present and it is characterized by mild dysmorphisms such as downslanting palpebral fissures, bilateral epicanthic folds, depressed nasal bridge, bulbous nasal tip, tented upper lip, everted lower lip and large ears. The relationship between this microdeletion syndrome and the congenital variant of Rett syndrome due to point mutations in one of the genes included in the deleted region, FOXG1, is discussed.

  14. Congenital cataract, microphthalmia, hypoplasia of corpus callosum and hypogenitalism: report and review of Micro syndrome.

    PubMed

    Derbent, Murat; Agras, Pinar Isik; Gedik, Sansal; Oto, Sibel; Alehan, Füsun; Saatçi, Umit

    2004-07-30

    We report on a 7-month-old boy with Micro syndrome who was referred for assessment of mental-motor retardation and reduced vision with cataract. The characteristics of Micro syndrome are mental retardation, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism. The differential diagnosis includes cerebro-oculo-facio-skeletal syndrome (COFS); a syndrome involving cataract, arthrogryposis, microcephaly, and kyphoscoliosis (CAMAK); a syndrome with cataract, microcephaly, failure to thrive, and kyphoscoliosis (CAMFAK); Martsolf syndrome; Neu-Laxova syndrome; Lenz microphthalmia syndrome; and Smith-Lemli-Opitz syndrome. Till date, no renal malformations have been reported in Micro syndrome. Our patient had fusion of the lower poles of the kidneys and his left kidney was ectopic. Ocular findings are the most reliable neonatal diagnostic signs of Micro syndrome. Minör anomalies in Micro syndrome may be subtle and therefore not of significant diagnostic value. Micro syndrome is an autosomal recessive trait. Till date, most reported cases have been in individuals of Muslim origin. In countries with high rates of consanguineous marriage, such as Turkey, it is important that physicians be able to recognize this syndrome. Micro syndrome should be considered in any infant with congenital cataract.

  15. Prenatal Diagnosis of Non-Syndromic Congenital Heart Defects

    PubMed Central

    Ailes, Elizabeth C.; Gilboa, Suzanne M.; Riehle-Colarusso, Tiffany; Johnson, Candice Y.; Hobbs, Charlotte A.; Correa, Adolfo; Honein, Margaret A.

    2015-01-01

    Objectives Congenital heart defects (CHDs) occur in nearly 1% of live births. We sought to assess factors associated with prenatal CHD diagnosis in the National Birth Defects Prevention Study (NBDPS). Methods We analyzed data from mothers with CHD-affected pregnancies from 1998–2005. Prenatal CHD diagnosis was defined as affirmative responses to questions about abnormal prenatal ultrasounds and/or fetal echocardiography obtained during a structured telephone interview. Results Fifteen percent (1,097/7,299) of women with CHD-affected pregnancies (excluding recognized syndromes and single-gene disorders) reported receiving a prenatal CHD diagnosis. Prenatal CHD diagnosis was positively associated with advanced maternal age, family history of CHD, type 1 or type 2 diabetes, twin or higher order gestation, CHD complexity and presence of extracardiac defects. Prenatal CHD diagnosis was inversely associated with maternal Hispanic race/ethnicity, prepregnancy overweight or obesity, and pre-existing hypertension. Prenatal CHD diagnosis varied by time to NBDPS interview and NBDPS study site. Conclusions Further work is warranted to identify reasons for the observed variability in maternal reports of prenatal CHD diagnosis and the extent to which differences in health literacy or health system factors such as access to specialized prenatal care and/or fetal echocardiography may account for such variability. PMID:24222433

  16. Ethical considerations with the management of congenital central hypoventilation syndrome.

    PubMed

    Massie, John; Gillam, Lynn

    2015-05-01

    Congenital central hypoventilation syndrome (CCHS) is a well-recognized disorder of the autonomic nervous system caused by mutations in the PHOX2B gene. The most characteristic feature is failure of ventilatory control, resulting in the need for respiratory support while asleep, and in some cases when awake also. Most cases present in infancy or early childhood. Technological advances allow patients with mild to moderate phenotypesto receive adequate support by non-invasive ventilation (NIV), or diaphragm pacing (or combination of the two) avoiding the need for long-term ventilation by tracheostomy. Daytime functioning of patients with CCHS who require sleep-time ventilation only is expected to be good, with some additional surveillance to ensure they don't accidentally fall asleep without respiratory support available. Some children with CCHS have other complications, such as Hirschprung's disease, learning difficulties, and cardiac arrhythmias (leading in some instances to heart block and the requirement for a pacemaker). In a few cases, patients can develop neurogenic malignancies. Parents bear a significant burden for the care of their child with CCHS including provision of NIV at home, close monitoring, and regular surveillance for complications. Information about patients with CCHS comes from databases in the United States and Europe, but these don't include infants or children for whom ventilator support was not offered. In this paper we use a case study to explore the ethical issues of provision of treatment, or non-treatment, of children with CCHS.

  17. Rubella 1974 and its aftermath, congenital rubella syndrome.

    PubMed Central

    Faulkner, R. S.; Gough, D. A.

    1976-01-01

    An epidemic of rubella reached its peak in the Atlantic provinces in 1974, subsiding in early 1975. With the exception of Quebec the remainder of Canada showed a reverse trend, with a large increase in the numbers of cases reported in the first 41/2 months of 1975. The Halifax virus laboratory reported 106 serologically proven cases of rubella in 1974, 44 of them in pregnant women. In the aftermath of the epidemic many infants were born with the congenital rubella syndrome (CRS). A study carried out from Sept. 1, 1974 through Apr. 30, 1975 showed an 80% correlation between clinical diagnosis and the presence of rubella-specific IgM antibodies in 35 of these infants. Of the 23 infants in whom the diagnosis of CRS was made by laboratory or clinical findings or both, laboratory criteria were met in 20 (87.0%), clinical criteria in 19 (82.6%) and both laboratory and clinical criteria in 16 (69.6%). PMID:1253045

  18. Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future

    PubMed Central

    2015-01-01

    The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime. PMID:26790381

  19. Dilated Basilar Arteries in Patients with Congenital Central Hypoventilation Syndrome

    PubMed Central

    Kumar, Rajesh; Nguyen, Haidang D.; Macey, Paul M.; Woo, Mary A.; Harper, Ronald M.

    2009-01-01

    Congenital central hypoventilation syndrome (CCHS) patients show hypoventilation during sleep and severe autonomic impairments, including aberrant cardiovascular regulation. Abnormal sympathetic patterns, together with increased and variable CO2 levels, lead to the potential for sustained cerebral vasculature changes. We performed high-resolution T1-weighted imaging in 13 CCHS and 31 control subjects using a 3.0-Tesla magnetic resonance imaging scanner, and evaluated resting basilar and bilateral middle cerebral artery cross-sections. Two T1-weighted image series were acquired; images were averaged and reoriented to common space, and regions containing basilar and both middle cerebral arteries were oversampled. Cross-sections of the basilar and middle cerebral arteries were manually outlined to calculate cross-sectional areas, and differences between and within groups were evaluated. Basilar arteries in CCHS were significantly dilated over control subjects, but both middle cerebral artery cross-sections were similar between groups. No significant differences appeared between left and right middle cerebral arteries within either group. Basilar artery dilation may result from differential sensitivity to high CO2 over other vascular beds, damage to serotonergic or other chemosensitive cells accompanying the artery, or enhanced microvascular resistance, and that dilation may impair tissue perfusion, leading to further neural injury in CCHS. PMID:19822189

  20. Congenital diaphragmatic hernia in a case of patau syndrome: a rare association.

    PubMed

    A, Jain; P, Kumar; A, Jindal; Yk, Sarin

    2015-01-01

    Congenital diaphragmatic hernia (CDH) occurs in 5-10% associated with chromosomal abnormalities like, Pallister Killian syndrome, Trisomy 18, and certain deletions.. Association of CDH with trisomy 13 (Patau syndromes) is very rare. Here, we report such an unusual association, where surgical repair was done, but eventually the case succumbed as a result of multiple fatal co-morbidities.

  1. Persistent Intraocular Rubella Infection in a Patient with Fuchs' Uveitis and Congenital Rubella Syndrome

    PubMed Central

    Varga, Zsolt; Parmar, Dipak; Brown, Kevin E.

    2013-01-01

    There is growing evidence for the role of rubella virus in Fuchs' uveitis syndrome (FUS). This report is the first to show persistent intraocular rubella virus in a 28-year-old man with congenital rubella syndrome (CRS), who presented with blurred vision and was diagnosed with FUS. PMID:23426927

  2. RFT1-congenital disorder of glycosylation (CDG) syndrome: a cause of early-onset severe epilepsy.

    PubMed

    Aeby, Alec; Prigogine, Cynthia; Vilain, Catheline; Malfilatre, Geneviève; Jaeken, Jaak; Lederer, Damien; Van Bogaert, Patrick

    2016-03-01

    RFT1-congenital disorder of glycosylation (CDG) syndrome, a recessive N-glycosylation disorder caused by mutation in the RFT1 gene, is a very rare subtype of CDG syndrome associated with deafness, developmental delay, and non-specific epilepsy. The aim of this report is to describe the electroclinical presentation of epilepsy associated with this condition. [Published with video sequences online].

  3. Congenital Diaphragmatic Hernia in a Case of Patau Syndrome: A Rare Association

    PubMed Central

    A, Jain; P, Kumar; A, Jindal; Yk, Sarin

    2015-01-01

    Congenital diaphragmatic hernia (CDH) occurs in 5-10% associated with chromosomal abnormalities like, Pallister Killian syndrome, Trisomy 18, and certain deletions.. Association of CDH with trisomy 13 (Patau syndromes) is very rare. Here, we report such an unusual association, where surgical repair was done, but eventually the case succumbed as a result of multiple fatal co-morbidities. PMID:26034714

  4. Major congenital anomalies in babies born with Down syndrome: a EUROCAT population-based registry study.

    PubMed

    Morris, Joan K; Garne, Ester; Wellesley, Diana; Addor, Marie-Claude; Arriola, Larraitz; Barisic, Ingeborg; Beres, Judit; Bianchi, Fabrizio; Budd, Judith; Dias, Carlos Matias; Gatt, Miriam; Klungsoyr, Kari; Khoshnood, Babak; Latos-Bielenska, Anna; Mullaney, Carmel; Nelen, Vera; Neville, Amanda J; O'Mahony, Mary; Queisser-Luft, Annette; Randrianaivo, Hanitra; Rankin, Judith; Rissmann, Anke; Rounding, Cath; Sipek, Antonin; Stoianova, Sylvia; Tucker, David; de Walle, Hermien; Yevtushok, Lyubov; Loane, Maria; Dolk, Helen

    2014-12-01

    Previous studies have shown that over 40% of babies with Down syndrome have a major cardiac anomaly and are more likely to have other major congenital anomalies. Since 2000, many countries in Europe have introduced national antenatal screening programs for Down syndrome. This study aimed to determine if the introduction of these screening programs and the subsequent termination of prenatally detected pregnancies were associated with any decline in the prevalence of additional anomalies in babies born with Down syndrome. The study sample consisted of 7,044 live births and fetal deaths with Down syndrome registered in 28 European population-based congenital anomaly registries covering seven million births during 2000-2010. Overall, 43.6% (95% CI: 42.4-44.7%) of births with Down syndrome had a cardiac anomaly and 15.0% (14.2-15.8%) had a non-cardiac anomaly. Female babies with Down syndrome were significantly more likely to have a cardiac anomaly compared to male babies (47.6% compared with 40.4%, P < 0.001) and significantly less likely to have a non-cardiac anomaly (12.9% compared with 16.7%, P < 0.001). The prevalence of cardiac and non-cardiac congenital anomalies in babies with Down syndrome has remained constant, suggesting that population screening for Down syndrome and subsequent terminations has not influenced the prevalence of specific congenital anomalies in these babies.

  5. Active surveillance for congenital rubella syndrome in Yangon, Myanmar.

    PubMed Central

    Thant, Kyaw-Zin; Oo, Win-Mar; Myint, Thein-Thein; Shwe, Than-Nu; Han, Aye-Maung; Aye, Khin-Mar; Aye, Kay-Thi; Moe, Kyaw; Thein, Soe; Robertson, Susan E.

    2006-01-01

    OBJECTIVE: Rubella vaccine is not included in the immunization schedule in Myanmar. Although surveillance for outbreaks of measles and rubella is conducted nationwide, there is no routine surveillance for congenital rubella syndrome (CRS). Therefore, we organized a study to assess the burden of CRS. METHODS: From 1 December 2000 to 31 December 2002 active surveillance for CRS was conducted among children aged 0-17 months at 13 hospitals and 2 private clinics in Yangon, the capital city. Children with suspected CRS had a standard examination and a blood sample was obtained. All serum samples were tested for rubella-specific IgM; selected samples were tested for rubella-specific IgG and for rubella RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). FINDINGS: A total of 81 children aged 0-17 months were suspected of having CRS. Of these, 18 children had laboratory-confirmed CRS (7 were IgM positive; 7 were RT-PCR positive; and 10 were IgG positive at > 6 months of age). One additional child who tested positive by RT-PCR and whose mother had had rubella during pregnancy but who had a normal clinical examination was classified as having congenital rubella infection. During 2001-02 no rubella outbreaks were detected in Yangon Division. In the 31 urban townships of Yangon Division, the annual incidence was 0.1 laboratory-confirmed cases of CRS per 1000 live births. CONCLUSION: This is the first population-based study of CRS incidence from a developing country during a rubella-endemic period; the incidence of CRS is similar to endemic rates found in industrialized countries during the pre-vaccine era. Rubella-specific IgG tests proved practical for diagnosing CRS in children aged > 6 months. This is one of the first studies to report on the use of rubella-specific RT-PCR directly on serum samples; further studies are warranted to confirm the utility of this method as an additional means of diagnosing CRS. PMID:16501710

  6. A case of Moebius syndrome presenting with congenital bilateral vocal cord paralysis.

    PubMed

    Kanemoto, Nobuko; Kanemoto, Katsuyoshi; Kamoda, Tomohiro; Hasegawa, Makoto; Arinami, Tadao

    2007-08-01

    We describe a female infant with bilateral facial paralysis and abducens palsy. To the best of our knowledge, this is the first report of Moebius syndrome presenting with congenital bilateral vocal cord paralysis (CBVCP). Although CBVCP can be part of a recognizable syndrome, i.e. Down syndrome, 22q deletion syndrome, Robinow's syndrome and cerebro-oculo-facio-skeletal syndrome, no reports of Moebius syndrome with CBVCP were found in the literature. CBVCP is often associated with central nervous system abnormalities. However, our patient had no detectable brain abnormalities. The etiology of Moebius syndrome remains unknown. It is interesting that the clinical manifestations of Moebius syndrome can include CBVCP. However, the pathophysiology of CBVCP is unknown and further investigations into the etiology of Moebius syndrome are required.

  7. Congenital and drug-induced long-QT syndrome: an update

    PubMed Central

    Wehrens, X.H.T.; Doevendans, P.A.

    2004-01-01

    The congenital long-QT syndrome is a potentially life-threatening condition characterised clinically by prolonged QT intervals, syncope and sudden cardiac death. The abnormally prolonged repolarisation is the result of mutations in genes encoding cardiac ion channels. The diagnosis of long-QT syndrome is based on clinical, electrocardiographic, and genetic criteria. Beta-blocking therapy is important in the treatment of long-QT syndrome, although pacemakers and implantable cardioverter defibrillators (ICD) are useful in certain categories of patients. In the near future, mutation-specific treatment will probably become a novel approach to this potentially lethal syndrome. Drug-induced long-QT syndrome has been associated with silent mutations and common polymorphisms in potassium and sodium channel genes associated with congenital long-QT syndrome. Genetic screening for such mutations and polymorphisms may become an important instrument in preventing drug-induced 'torsades de pointes' arrhythmias in otherwise asymptomatic patients. PMID:25696318

  8. Modelling the incidence of congenital rubella syndrome in developing countries.

    PubMed

    Cutts, F T; Vynnycky, E

    1999-12-01

    Inclusion of rubella vaccine in the national immunization program was found to be implemented in less than one-third of the developing countries in a review conducted by WHO. This paper examines the incidence of congenital rubella syndrome (CRS) cases in developing countries using published rubella infection prevalence. Documented literature of previous studies and medical data on women attending antenatal clinics were gathered and rubella antibody prevalence was identified before the wide-scale rubella vaccination. A catalytic model was used in describing age-specific prevalence of rubella virus infection in given populations, while expressions for the average prevalence of susceptibility to infection and incidence of infection during gestation was used to estimate the incidence of infection among pregnant women. Using the data gathered from each country and WHO regions, an overall risk of 65% after infection in the first 16 weeks and zero risk of defect later in pregnancy was assumed to estimate the incidence of CRS. Results revealed that the estimated mean incidence of CRS per 100,000 live births was significantly lower in the eastern Mediterranean region (77.4, range 0-212) and higher in the Americas (175, range 0-598). On the other hand, the 1996 CRS mean estimate for developing countries was approximately 110,000, ranging from 14,000 to 308,000 cases. This study concludes with the stated need for an improved CRS program in developing countries as well as adequate data collection necessary for cost-effectiveness evaluation of potential global rubella control programs.

  9. A case of Klippel-Feil syndrome with congenital enlarged Eustachian tube.

    PubMed

    Jovankovičová, A; Jakubíková, J; Durovčíková, D

    2012-04-01

    The Klippel-Feil syndrome is a congenital anomaly characterized by fusion of the cervical vertebrae. It is often associated with serious congenital anomalies of the nervous, cardiovascular and urogenital systems. One of the anomalies which have not been thoroughly investigated to date are that accompanying Klippel-Feil syndrome and enlarged Eustachian tube. We report a case of type III Klippel-Feil syndrome with associated rib anomalies such as hypoplastic and bifid ribs, scoliosis and elevated scapula (Sprengel's disease). The patient also presented hemifacial microsomia and central facial palsy of the lower right side of the face, urogenital and cardiovascular anomaly, congenital anorectal atresia and right-sided congenital aural atresia with microtia. Computer tomography of temporal bone showed abnormal extension of the right Eustachian tube with anomalies of the middle and inner ear on this particular side. In this case report we discuss the associated anomalies of the patient with Klippel-Feil syndrome. The aim of this case report is to draw attention to very rare case of patient with Klippel-Feil syndrome and enlarged pharyngotympanic tube.

  10. Congenital diaphragmatic hernia is part of the new 15q24 microdeletion syndrome.

    PubMed

    Van Esch, Hilde; Backx, Liesbeth; Pijkels, Elly; Fryns, Jean-Pierre

    2009-01-01

    The recurrent microdeletion 15q24 syndrome is rare with only 5 cases reported thus far. Here we describe an additional patient with this deletion, presenting with many features common to this syndrome, including developmental delay, loose connective tissue, digital and genital anomalies and a distinct facial gestalt. Interestingly, in addition, this patient has a large congenital diaphragmatic hernia, as was described in one other patient with a 15q24 microdeletion, indicating that this feature might be part of the syndrome. Chromosome 15q24 has a highly polymorphic architecture that is prone to genomic rearrangements underlying this novel microdeletion syndrome.

  11. Pulmonary Hypertension in a Patient With Congenital Heart Defects and Heterotaxy Syndrome

    PubMed Central

    Yousuf, Tariq; Kramer, Jason; Jones, Brody; Keshmiri, Hesam; Dia, Muhyaldeen

    2016-01-01

    Background: Heterotaxy syndrome, also called isomerism, is a condition in which abdominal and thoracic organs are located in abnormal body positions. Pulmonary hypertension (PHTN) is an uncommon clinical feature of heterotaxy syndrome. Case Report: We describe the case of a 26-year-old male who developed PHTN as a rare manifestation of heterotaxy syndrome. To our knowledge, PHTN has never been reported as a prominent clinical feature in a patient with heterotaxy syndome and congenital cardiac abnormalities. Conclusion: It is important for the clinician to be aware of potentially serious consequences of PHTN in the setting of heterotaxy syndrome. PMID:27660582

  12. A family with Townes-Brocks syndrome with congenital hypothyroidism and a novel mutation of the SALL1 gene.

    PubMed

    Choi, Won Ik; Kim, Ji Hye; Yoo, Han Wook; Oh, Sung Hee

    2010-12-01

    Townes-Brocks syndrome (TBS) is a rare autosomal dominant congenital disorder caused by mutations in the SALL1 gene. Its signs and symptoms overlap with other genetic syndromes, including VACTERL association, Pendred syndrome, Baller-Gerold syndrome, and cat eye syndrome. Structural vertebral abnormalities, hypoplasia of the thumb, and radial bone abnormalities, which are not usually associated with TBS, help in the differential diagnosis of these syndromes. We report the case of a family whose members were diagnosed with TBS with congenital hypothyroidism and had a novel SALL1 gene mutation.

  13. Congenital bilateral perisylvian syndrome (CBPS): do concomitant esophageal malformations indicate a poor prognosis?

    PubMed

    Küker, W; Friese, S; Riethmüller, J; Krägeloh-Mann, I

    2000-12-01

    Congenital bilateral perisylvian syndrome (CBPS) is a syndrome of cortical malformation characterized by faciopharyngoglossomasticatory diplegia. We report on two cases of CBPS with associated esophageal malformations and a poor mental and motor development. The association of CBPS and esophageal malformations may indicate a subgroup of patients with a very early prenatal injury, characterised by a bad prognosis due to severe cortical disorganization. However, it can not be excluded that the association of CBPS and esophageal malformation is purely coincidental.

  14. Congenital heart block associated with Sjögren syndrome: case report

    PubMed Central

    Moutasim, Karwan A; Shirlaw, Penelope J; Escudier, Michael P; Poate, Timothy WJ

    2009-01-01

    Background Congenital heart block is a rare complication of pregnancy associated with Sjögren Syndrome that may result in the death of the foetus or infant, or the need for pacing in the newborn or at a later stage. Case report The case is presented of a 64-year-old patient with primary Sjögren Syndrome and a history of having given birth to two sons with congenital heart block, both of whom required pacing several years later. Conclusion The literature relating to this association is discussed including the suggested mechanism, long-term outcome of mothers of children with congenital heart block and preventive treatment strategies. PMID:19638228

  15. Maternal manifestation of Ballantyne's syndrome occurring concomitantly with the development of fetal congenital mesoblastic nephroma.

    PubMed

    Takahashi, Hironori; Matsubara, Shigeki; Kuwata, Tomoyuki; Ohkuchi, Akihide; Mukoda, Yukiko; Saito, Koyomi; Usui, Rie; Suzuki, Mitsuaki

    2014-04-01

    Various fetal or placental disorders cause Ballantyne's (mirror) syndrome. For the first time, we report a maternal manifestation of Ballantyne's syndrome occurring concomitantly with the development of fetal congenital mesoblastic nephroma (CMN). In a pregnant woman with a CMN fetus, lung edema, hypertension, hyperthyroidism, and high serum human chorionic gonadotrophin level occurred, all of which characterize maternal manifestation of Ballantyne's syndrome. The fetus and placenta were devoid of 'edema', lacking 'triple edema', and thus this condition was not diagnosed as Ballantyne's syndrome; however, we considered this condition as the maternal manifestation of Ballantyne's syndrome. We performed emergent cesarean section at 28 weeks. Delivery acutely ameliorated maternal symptoms. Tumor was resected and was confirmed as CMN. Maternal manifestations of Ballantyne's syndrome, such as lung edema and hypertension, can occur in a mother with fetal CMN even without fetal and/or placental edema. The clinical course of this patient may suggest an etiology of Ballantyne's syndrome.

  16. Early Growth and Neurologic Outcomes of Infants with Probable Congenital Zika Virus Syndrome

    PubMed Central

    Ganz, Jucelia Sousa Santos; Sousa, Patricia da Silva; Doriqui, Maria Juliana Rodvalho; Ribeiro, Marizelia Rodrigues Costa; Branco, Maria dos Remédios Freitas Carvalho; Queiroz, Rejane Christine de Sousa; Pacheco, Maria de Jesus Torres; Vieira da Costa, Flavia Regina; Silva, Francelena de Sousa; Simões, Vanda Maria Ferreira; Pacheco, Marcos Antonio Barbosa; Lamy-Filho, Fernando; Lamy, Zeni Carvalho; Soares de Britto e Alves, Maria Teresa Seabra

    2016-01-01

    We report the early growth and neurologic findings of 48 infants in Brazil diagnosed with probable congenital Zika virus syndrome and followed to age 1–8 months. Most of these infants had microcephaly (86.7%) and craniofacial disproportion (95.8%). The clinical pattern included poor head growth with increasingly negative z-scores, pyramidal/extrapyramidal symptoms, and epilepsy. PMID:27767931

  17. Effect of Congenital Heart Defects on Language Development in Toddlers with Down Syndrome

    ERIC Educational Resources Information Center

    Visootsak, J.; Hess, B.; Bakeman, R.; Adamson, L. B.

    2013-01-01

    Background: Down syndrome (DS, OMIM #190685) is the most commonly identified genetic form of intellectual disability with congenital heart defect (CHD) occurring in 50% of cases. With advances in surgical techniques and an increasing lifespan, this has necessitated a greater understanding of the neurodevelopmental consequences of CHDs. Herein, we…

  18. Influence of Congenital Heart Defect on Psychosocial and Neurodevelopmental Outcomes in Children with Down Syndrome

    PubMed Central

    Visootsak, Jeannie; Huddleston, Lillie; Buterbaugh, Allison; Perkins, Adrienne; Sherman, Stephanie; Hunter, Jessica

    2015-01-01

    Objective To evaluate the family psychosocial outcomes of children with Down syndrome and atrioventricular septal defect, and examine the impact of these variables on the child’s neurodevelopmental outcome. Methods This was a cross-sectional study that consisted of 57 children with Down syndrome (20 cases and 37 controls), approximately 12–14 months of age. In both groups, we assessed the development of the child, the quality of the child’s home environment, and parenting stress. Results Compared with the Down syndrome without congenital heart defect group, the atrioventricular septal defect group revealed lower scores in all developmental domains, less optimal home environments, and higher parental stress. Significant differences in development were seen in the areas of cognition (p=0.04), expressive language (p=0.05), and gross motor (p<0.01). The Home Observation for Measurement of the Environment revealed significant differences in emotional and verbal responsiveness of the mother between the two groups. The Parenting Stress Index revealed the Down syndrome with atrioventricular septal defect group had a significantly higher child demandingness subdomain scores compared to the Down syndrome without congenital heart defect group. Conclusions The diagnosis of a congenital heart defect in addition to the diagnosis of Down syndrome may provide additional stress to the child and parents, elevating parental concern and disrupting family dynamics, resulting in further neurodevelopmental deficits. Finding that parental stress and home environment may play a role in the neurodevelopmental outcomes may prompt new family-directed interventions and anticipatory guidance for the families of children with Down syndrome who have a congenital heart defect. PMID:25683160

  19. Congenital scoliosis in Smith-Magenis syndrome: a case report and review of the literature.

    PubMed

    Li, Zheng; Shen, Jianxiong; Liang, Jinqian; Sheng, Lin

    2015-05-01

    The Smith-Magenis syndrome (SMS) is a complex and rare congenital condition that is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioral, and neurocognitive abnormalities, as well as variable multisystemic manifestations. Little is reported about spinal deformity associated with this syndrome.This study is to present a case of scoliosis occurring in the setting of SMS and explore the possible mechanisms between the 2 diseases.The patient is a 13-year-old Chinese female with congenital scoliosis and Tetralogy of Fallot, mental retardation, obstructive sleep apnea, hypertrophy of tonsil, conductive hearing loss, and agenesis of the epiglottis. An interphase fluorescent in situ hybridization at chromosome 17p11.2 revealed a heterozygous deletion, confirming a molecular diagnosis of SMS. She underwent a posterior correction at thoracic 1-lumbar 1 (T1-L1) levels, using the Moss-SI spinal system. At 6-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of correction.Congenital cardiac disease, immunodeficiency, and severe behavioral problems can affect the surgical outcome following spine fusion and need to be taken into consideration for the surgeon and anesthesiologist. Scoliosis is not uncommon among patients with SMS, and there is a potential association between congenital scoliosis and SMS. The potential mechanisms in the pathogenesis of congenital scoliosis of SMS included retinoic acid-induced 1 (RAI1) microdeletion and RAI1 gene point mutation.

  20. Profuse congenital familial milia with absent dermatoglyphics (Basan's Syndrome): description of a new family.

    PubMed

    Luna, Paula Carolina; Larralde, Margarita

    2012-01-01

    Milia are common, small, keratin-containing cysts frequently seen in all age groups. They may arise spontaneously or develop after a variety of stimuli. They can be found alone or as part of syndromes. We present a female neonate born not only with profuse facial milia, but also with acral bullae and absent dermatoglyphics. Similar features were seen in several members of her family. These findings correspond to the syndrome known as Basan's syndrome, a rare autosomal-dominant inherited dermatosis characterized by profuse congenital milia, transient neonatal acral bullae, and absence of dermatoglyphics.

  1. Congenital vertical talus in Cri du Chat Syndrome: a case report

    PubMed Central

    2013-01-01

    Background Congenital vertical talus is a rare deformity of the foot which can cause substantial pain and disability. Its incidence is approximately 1 in 100,000 live births. It has an association with other neuromuscular abnormalities and identified genetic syndromes in 50% of cases [1-5]. This report presents a case of congenital vertical talus in an infant with Cri du Chat Syndrome (CdCS) which - to our knowledge - has not been previously reported. Case presentation A 2 week-old Caucasian, male infant was referred for congenital feet abnormalities and a “clicky” hip at the post-natal baby check. The diagnosis was vertical talus of the right foot and oblique talus of the left foot. Treatment involved serial plaster casts in the “reverse-Ponseti” position until surgery 16 weeks later. The correction was maintained and the feet remain in good position at follow-up. General concern over the infant’s development, failing to reach appropriate milestones, prompted paediatric referral. Genetic analysis was finally carried out, giving a diagnosis of Cri du Chat syndrome at two and a half years of age. Conclusion In light of other reports of chromosomal anomalies causing congenital vertical talus, the learning point from this case is to investigate early for possible aetiologies, not only spinal/neuromuscular, but also those of a genetic basis. PMID:23849392

  2. Life and Death of a Child with Down Syndrome and a Congenital Heart Condition: Experiences of Six Couples

    ERIC Educational Resources Information Center

    Reilly, Deirdre; Huws, Jaci; Hastings, Richard; Vaughan, Frances

    2010-01-01

    Individuals with Down syndrome are at increased risk of congenital heart conditions (CHCs), and mortality is higher in people with Down syndrome and a CHC than those without (J. C. Vis et al., 2009). As a consequence, parents of children with Down syndrome and a CHC are more likely to outlive their child. In this research, semistructured…

  3. Evaluation of congenital dysautonomia other than Riley-Day syndrome.

    PubMed

    Alvarez, E; Ferrer, T; Pérez-Conde, C; López-Terradas, J M; Pérez-Jiménez, A; Ramos, M J

    1996-02-01

    We report on four children, from different families, who suffer from a congenital autonomic disorder, presumably inherited. Three of them have a sensory neuropathy but do not fit any described hereditary sensory and autonomic neuropathy. All four were examined along with some of their immediate family members. We assessed the cardiovagal, sympathetic adrenergic and sympathetic cholinergic functions with a battery of non-invasive tests. Results demonstrated that sudomotor and cardiovascular orthostatic regulation exhibited the greatest abnormalities, pointing to a predominant impairment of sympathetic components, both cholinergic and adrenergic. The overall examination showed a heterogeneous group of congenital dysautonomia, exclusive of Riley-Day or other recognized hereditary sensory and autonomic neuropathies. We emphasize the importance of studying whole family groups to diagnose subclinical impairment and to provide correct genetic counselling.

  4. A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy.

    PubMed

    Okamoto, Nobuhiko; Toribe, Yasuhisa; Nakajima, Tohru; Okinaga, Takeshi; Kurosawa, Kenji; Nonaka, Ikuya; Shimokawa, Osamu; Matsumoto, Noamichi

    2002-01-01

    Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene -/- mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome.

  5. Down syndrome: Molecular mapping of the congenital heart disease and duodenal stenosis

    SciTech Connect

    Korenburg, J.R. ); Bradley, C.; Disteche, C.M. )

    1992-02-01

    Down syndrome (DS) is a major cause of congenital heart and gut disease and mental retardation. DS individuals also have characteristic facies, hands, and dermatoglyphics, in addition to abnormalities of the immune system, and increased risk of leukemia, and an Alzheimer-like dementia. Although their molecular basis is unknown, recent work on patients with DS and partial duplications of chromosome 21 has suggested small chromosomal regions located in band q22 that are likely to contain the genes for some of these features. The authors now extend these analyses to define molecular markers for the congenital heart disease, the duodenal stenosis, and an 'overlap' region for the facial and some of the skeletal features. They report the clinical, cytogenetic, and molecular analysis of two patients. These studies provide the molecular basis for the construction of a DS phenotypic map and focus the search for genes responsible for the physical features, congenital heart disease, and duodenal stenosis of DS.

  6. Genotype–Phenotype Correlation of Congenital Anomalies in Multiple Congenital Anomalies Hypotonia Seizures Syndrome (MCAHS1)/ PIGN-Related Epilepsy

    PubMed Central

    Fleming, Leah; Lemmon, Monica; Beck, Natalie; Johnson, Maria; Mu, Weiyi; Murdock, David; Bodurtha, Joann; Hoover-Fong, Julie; Cohn, Ronald; Bosemani, Thangamadhan; Barañano, Kristin; Hamosh, Ada

    2016-01-01

    Mutations in PIGN, resulting in multiple congenital anomalies-hypotonia-seizures syndrome, a glycosylphosphatidylinositol anchor deficiency, have been published in four families to date. We report four patients from three unrelated families with epilepsy and hypotonia in whom whole exome sequencing yielded compound heterozygous variants in PIGN. As with previous reports Patients 1 and 2 (full siblings) have severe global developmental delay, gastroesophageal reflux disease, and minor dysmorphic features, including high palate, bitemporal narrowing, depressed nasal bridge, and micrognathia; Patient 3 had early global developmental delay with later progressive spastic quadriparesis, intellectual disability, and intractable generalized epilepsy; Patient 4 had bilateral narrowing as well but differed by the presence of hypertelorism, markedly narrow palpebral fissures, and long philtrum, had small distal phalanges of fingers 2, 3, and 4, absent distal phalanx of finger 5 and similar toe anomalies, underdeveloped nails, unusual brain anomalies, and a more severe early clinical course. These patients expand the known clinical spectrum of the disease. The severity of the presentations in conjunction with the patients’ mutations suggest a genotype–phenotype correlation in which congenital anomalies are only seen in patients with biallelic loss-of-function. In addition, PIGN mutations appear to be panethnic and may be an underappreciated cause of epilepsy. PMID:26394714

  7. Niikawa-Kuroki (Kabuki) syndrome with congenital sensorineural deafness: evidence for a wide spectrum of inner ear abnormalities.

    PubMed

    Tekin, Mustafa; Fitoz, Suat; Arici, Serap; Cetinkaya, Ergun; Incesulu, Armagan

    2006-05-01

    Hearing loss, mainly due to recurrent otitis media, has been reported in approximately 40% of individuals with Niikawa-Kuroki (Kabuki) syndrome (NKS). Sensorineural hearing loss leading to congenital or prelingual deafness has been described rarely. We have identified two unrelated individuals with Niikawa-Kuroki syndrome among 535 probands who have severe to profound sensorineural deafness. Bilateral absence of the cochlea with dilated dysplastic vestibule and unilateral enlarged vestibule were demonstrated in these two individuals. In conclusion, Niikawa-Kuroki syndrome should be kept in mind when evaluating an individual with congenital deafness and a wide spectrum of inner ear abnormalities occurs in this syndrome.

  8. Co-occurrence of congenital hydronephrosis and FOXL2-associated blepharophimosis, ptosis, epicanthus inversus syndrome (BPES).

    PubMed

    Gulati, Reena; Verdin, Hannah; Halanaik, Dhanapathi; Bhat, B Vishnu; De Baere, Elfride

    2014-10-01

    Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is an autosomal dominantly inherited congenital malformation of the eyelids. Diagnostic criteria include blepharophimosis, ptosis, epicanthus inversus and telecanthus. Type І BPES has additional features of premature ovarian failure and female infertility, while type ІІ occurs isolated. We report a two-year old male child with typical features of BPES and bilateral congenital hydronephrosis. The child, first-born to non-consanguineous parents, presented to us with hypertension. Congenital hydronephrosis and reduced renal function were confirmed by renal dynamic scan. Pyeloplasty and stent placement were performed with subsequent resolution of hypertension. On follow up, growth and development are appropriate for age. His father has similar but less severe features of BPES. Sequencing of the FOXL2 gene revealed a heterozygous FOXL2 mutation c.672_701dup, which is a recurrent 30-bp duplication leading to expansion of the polyalanine tract (p.Ala225_Ala234dup), in both father and son. Additional atypical clinical features have been reported previously in BPES patients with this mutation. However, this is the first report of a renal congenital anomaly in a BPES patient with this or other mutations. Although a pleiotropic effect of the FOXL2 mutation cannot be excluded, the co-occurrence of congenital hydronephrosis and BPES may represent two different entities.

  9. A new autosomal recessive congenital contractural syndrome in an Israeli Bedouin kindred.

    PubMed

    Landau, Daniella; Mishori-Dery, Anat; Hershkovitz, Reli; Narkis, Ginat; Elbedour, Khalil; Carmi, Rivka

    2003-02-15

    We describe 23 cases with a syndrome of congenital contractures belonging to a large, inbred Israeli-Bedouin kindred. The phenotype described is similar to the Finnish type lethal congenital contracture syndrome yet differs in the following ways: by some additional craniofacial/ocular findings, by the lack of hydrops, multiple pterygia, and fractures, and by the normal duration of pregnancy. The major unique and previously undescribed clinical feature in our patients is a markedly distended urinary bladder as well as other urinary abnormalities. The vast majority of the cases died shortly after birth. Sonographic prenatal diagnosis was possible as early as 15 weeks gestation by demonstrating fetal akinesia, limb contractures, hydramnios, and distended urinary bladder. Linkage to 5q and 9q34 loci has been excluded.

  10. Long-term bosentan treatment of complex congenital heart disease and Eisenmenger's syndrome.

    PubMed

    Díaz-Caraballo, Eva; González-García, Ana E; Reñones, Margarita; Sánchez-Recalde, Angel; García-Río, Francisco; Oliver-Ruiz, José M

    2009-09-01

    The BREATHE-5 study demonstrated that bosentan, an oral endothelin receptor antagonist, provides clinical benefits in patients with Eisenmenger's syndrome. As a result, the European Medicines Agency (EMEA) approved its use for this indication. However, follow-up in that study was limited to 16 weeks and patients with complex congenital heart disease were excluded. We assessed the effect of long-term bosentan treatment in 10 patients with complex congenital heart disease and Eisenmenger's syndrome. In the mean clinical follow-up period of 25 months, all patients reached the target dose without developing side effects and without experiencing a change in arterial oxygen consumption at either rest or maximal exercise. Moreover, there were significant changes in clinical parameters: NYHA functional class improved from 3.3+/-0.7 to 2.5+/-0.9 (P=.002) and the 6-minute walk distance increased from 266+/-161 m to 347+/-133 m (P=.015).

  11. Three Novel Mutations in the NPHS1 Gene in Vietnamese Patients with Congenital Nephrotic Syndrome

    PubMed Central

    Nguyen, Thi Kim Lien; Pham, Van Dem; Nguyen, Thu Huong; Pham, Trung Kien; Nguyen, Thi Quynh Huong

    2017-01-01

    Congenital nephrotic syndrome, a rare and severe disease, is inherited as an autosomal recessive trait. The disease manifests shortly after birth and occurs predominantly in families of Finnish origin but has now been observed in all countries and races. Mutations in the NPHS1 gene, which encodes nephrin, are the main causes of congenital nephrotic syndrome in patients. In this study, we report the first mutational analysis of the NPHS1 gene in three unrelated children from three different Vietnamese families. These patients were examined and determined to be suffering from congenital nephrotic syndrome in the Department of Pediatrics, Vietnam National Hospital of Pediatrics. All 29 exons and exon-intron boundaries of NPHS1 were analyzed by PCR and DNA sequencing. Genetic analysis of the NPHS1 gene revealed one compound heterozygous variant p.Glu117Lys, one heterozygous missense mutation p.Asp310Asn, and one heterozygous frame-shifting mutation (c.3250_3251insG causing p.Val1084Glyfs⁎12) in patient 1. In patient 2, one heterozygous variant p.Glu117Lys and one novel heterozygous missense mutation p.Ser324Ala were identified. Finally, a novel missense mutation p.Arg802Leu and a novel nonsense mutation (c.2442C>G causing p.K792⁎) were identified in patient 3.

  12. Congenital Horner Syndrome with Heterochromia Iridis Associated with Ipsilateral Internal Carotid Artery Hypoplasia

    PubMed Central

    Coulier, Julie; Rommel, Denis; Boschi, Antonella

    2015-01-01

    Background Horner syndrome (HS), also known as Claude-Bernard-Horner syndrome or oculosympathetic palsy, comprises ipsilateral ptosis, miosis, and facial anhidrosis. Case Report We report herein the case of a 67-year-old man who presented with congenital HS associated with ipsilateral hypoplasia of the internal carotid artery (ICA), as revealed by heterochromia iridis and confirmed by computed tomography (CT). Conclusions CT evaluation of the skull base is essential to establish this diagnosis and distinguish aplasia from agenesis/hypoplasia (by the absence or hypoplasia of the carotid canal) or from acquired ICA obstruction as demonstrated by angiographic CT. PMID:25749818

  13. Congenital Chylous Ascites and Ehlers-Danlos Syndrome Type VI

    PubMed Central

    Pohl, John; Esty, Brittany; Sempler, Jessica K.; Carey, John C.; O’Gorman, Molly A.

    2016-01-01

    We report the first observation of a patient with contgenital chylous ascites (CCA) and Ehlers-Danlos syndrome type VI due to primary lymphatic defect with additional vascular anomaly. CCA is a rare condition, and there is limited understanding of its pathophysiology and treatment options. We also review the patient’s treatment course mitigated with octreotide and total parenteral nutritional support, as there are no current established guidelines for CCA. Early recognition of possible association with Ehlers-Danlos syndrome is important for quick intervention and successful management of pediatric patients. PMID:28119937

  14. Successful surgical management of congenital Kasabach-Merritt syndrome.

    PubMed

    Pascal, Sébastien; Bettex, Quentin; Andre, Nicolas; Petit, Philippe; Casanova, Dominique; Degardin, Nathalie

    2017-01-01

    Since the first description of Kasabach-Merritt syndrome (KMS) in 1940, many treatments have been proposed combining pharmacologic and non-pharmacologic approaches, which can be effective on the pathology but can have adverse and unpredictable side-effects with long-term use. Herein we describe the solely surgical treatment of Kasabach-Merritt syndrome in a neonate with a severe and rapidly progressive thrombocytopenia. The patient's condition normalized at 7 days postoperatively, with rapid increase in platelet count and normalization of d-dimer concentration.

  15. Glaucoma in Fuchs' heterochromic cyclitis associated with congenital Horner's syndrome.

    PubMed

    Regenbogen, L S; Naveh-Floman, N

    1987-11-01

    We report a retrospective study of five patients with monocular Fuchs' heterochromic cyclitis associated with an ipsilateral Horner's syndrome. The minimum follow-up was 10 years. The presenting findings were cyclitis in three of the patients and heterochromia iridis associated with blepharoptosis in the other two. The major factors affecting all five patients were cataract and glaucoma. The intraocular pressure was uncontrolled even with maximal therapy, and antiglaucomatous surgery was performed in all cases. A short period of good postoperative control was followed by an intractable ocular hypertension, causing loss of useful vision in all patients. The remarkable combination of Horner's syndrome with glaucoma and their interaction is discussed.

  16. Congenital rubella syndrome, hyper-IgM syndrome and autoimmunity in an 18-year-old girl.

    PubMed

    Palacin, Pere Soler; Castilla, Yolanda; Garzón, Paula; Figueras, Concepció; Castellví, Joan; Español, Teresa

    2007-10-01

    Congenital rubella syndrome can be associated with disgammaglobulinaemia and autoimmune phenomena in adult and paediatric population. The aim of this article is to present the association between a congenital rubella syndrome with hypogammaglobulinaemia and hyper IgM diagnosed at the age of 8 months and autoimmune manifestations in an 18-year-old girl. A medical chart review of this patient since admission at our institution at 8 months of age was carried out. During infancy she presented the classical manifestations of a rubella syndrome (sensorineural deafness and brain calcifications in basal ganglia) with respiratory and gastrointestinal infections. She was also diagnosed of localised scleroderma and thyroiditis. She has been on intravenous immunoglobulin since diagnosis, with rapid normalisation of IgG and IgM levels, decreased incidence of infectious processes, but with persistent autoimmune phenomena. At 18 years of age she was admitted because of a thyroid mass. Fine needle aspiration biopsy was not conclusive and thyroidectomy was performed. Pathology studies showed no malignancy. She is now on replacement therapy with thyroid hormones. Our aim is to emphasise the importance of the association between autoimmune phenomena in patients with immunodeficiencies, even secondary to some infections, and the increased frequency of malignancies owing to the persistent immunologic defect in this syndrome.

  17. Congenital hypertrichosis (Were Wolf Syndrome): a case report.

    PubMed

    Alam, S T; Rahman, M M; Akhter, S; Hossain, M A; Islam, K A

    2012-07-01

    Hypertrichosis is abnormal increase in body hair, when it becomes extensive known as Were Wolf Syndrome. Any part of body can be affected and body hairs are longer and darker. Hairs may be of any type like lanugo, vellous or terminal. It may be present since birth or may occur later in life. A 8 years old boy was admitted in our hospital with excess body hair, he was diagnosed as a case of Were Wolf syndrome after excluding possible acquired causes of hypertrichosis. He had history of delayed developmental milestone and has been suffering from epilepsy. He was treated with developmental stimulation and anti epileptic drug. Then he was discharged after proper counseling.

  18. Autoimmune lymphoproliferative syndrome (ALPS): a case with congenital onset.

    PubMed

    Kahwash, Samir B; Fung, Bonita; Savelli, Stephanie; Bleesing, Jack J; Qualman, Stephen J

    2007-01-01

    We describe a case of autoimmune lymphoproliferative syndrome (ALPS), which is very unusual with regard to a clinical onset soon after birth, and a clinical picture dominated by splenomegaly, jaundice, and consumptive peripheral blood cytopenias, with minimal lymphadenopathy. Our documented close follow up demonstrated initial involvement of the spleen, followed by involvement of the bone marrow and the peripheral blood. The patient underwent bone marrow transplant and is alive and well 20 months after diagnosis.

  19. A new 48, XXYY/47, XYY syndrome associated with multiple skeletal abnormalities, congenital heart disease and mental retardation.

    PubMed

    Mutesa, Leon; Jamar, Mauricette; Hellin, Anne Cecile; Pierquin, Genevieve; Bours, Vincent

    2012-09-01

    While the XYY and XXYY syndromes have been several time described in patients, the combination of both syndromes in an individual is a rare event and may result in a severe phenotype. In the present observation, a boy with congenital scoliosis due to segmented thoracic hemivertebra associated with radioulnar synostosis and congenital heart disease is described. Chromosome G-banding and FISH analysis demonstrated a de novo mosaic karyotype 48, XXYY/47, XYY in this patient. To the best of our knowledge, this is the first report of a combination of XYY and XXYY syndromes.

  20. Characterization of ocular motor deficits in congenital facial weakness: Moebius and related syndromes.

    PubMed

    Rucker, Janet C; Webb, Bryn D; Frempong, Tamiesha; Gaspar, Harald; Naidich, Thomas P; Jabs, Ethylin Wang

    2014-04-01

    Congenital facial weakness is present in a heterogeneous group of conditions. Among them is Moebius syndrome, which has been defined as a disorder with congenital, non-progressive facial weakness and limited abduction of one or both eyes. It is typically attributed to agenesis of the abducens and facial cranial nerves. This paper details ocular motor findings of 40 subjects (23 months to 64 years; 24 females, 16 males) with congenital facial weakness: 38 presented at a Moebius Syndrome Conference and two were clinic patients. A new classification scheme of patterns based on ocular motor phenotype is presented. Of 40 subjects, 37 had bilateral and three had unilateral facial weakness. The most common ocular motor pattern (Pattern 1, n=17, 43%) was bilateral horizontal gaze palsy with intact vertical range. Pattern 2 (n=10, 26%) was bilateral horizontal gaze palsy with variable vertical limitations. Pattern 3, which was rare, was isolated abduction deficits (n=2, 5%). Others had full motility range and did not meet minimal criteria for the diagnosis of Moebius syndrome (Pattern 4, n=10, 26%). One subject was too severely affected to characterize. Abnormal vertical smooth pursuit was present in 17 (57%) of 30 subjects: nine with Pattern 1, five with Pattern 2, and three with Pattern 4. Abnormal vertical saccades were present in 10 (34%) of 29 subjects. Vertical saccades appeared slow in nine: six with Pattern 1 and three with Pattern 2. Vertical saccades were absent in one subject with Pattern 2. Abnormal vertical optokinetic nystagmus was present in 19 (68%) of 28 subjects: 10 with Pattern 1, six with Pattern 2, one with Pattern 3, and two with Pattern 4. Reduced convergence was present in 19 (66%) of 29 subjects: nine with Pattern 1, six with Pattern 2, one with Pattern 3, and three with Pattern 4. The most common pattern of ocular motor deficit in Moebius syndrome is bilateral horizontal gaze palsy from pontine abducens nuclear defects, rather than abducens nerve

  1. Lumbo-costo-vertebral syndrome with congenital lumbar hernia.

    PubMed

    Gupta, Lucky; Mala, Tariq Ahmed; Gupta, Rahul; Malla, Shahid Amin

    2014-01-01

    Lumbo-costo-vertebral syndrome (LCVS) is a set of rare abnormalities involving vertebral bodies, ribs, and abdominal wall. We present a case of LCVS in a 2-year-old girl who had a progressive swelling over left lumbar area noted for the last 12 months. Clinical examination revealed a reducible swelling with positive cough impulse. Ultrasonography showed a defect containing bowel loops in the left lumbar region. Chest x-ray showed scoliosis and hemivertebrae with absent lower ribs on left side. Meshplasty was done.

  2. Congenital pseudarthrosis of the clavicle causing thoracic outlet syndrome

    PubMed Central

    Watson, Hannah Isabella; Hopper, Graeme Philip; Kovacs, Peter

    2013-01-01

    A 7-year-old girl presented with an asymptomatic right supraclavicular swelling. Radiographs were interpreted as showing a non-union of her clavicle. No treatment was given at this time. However, she represented 12 years later with right upper limb pain and altered sensation. Examination revealed a positive Allen's test on the right. Repeat radiographs demonstrated a pseudarthrosis of the clavicle, associated with a secondary complication of thoracic outlet syndrome with vascular and neurological complications present. Non-operative management failed to relieve her symptoms. Operative intervention successfully treated her symptoms. PMID:23975919

  3. Emergence of Epidemic Zika Virus Transmission and Congenital Zika Syndrome: Are Recently Evolved Traits to Blame?

    PubMed Central

    2017-01-01

    ABSTRACT The mechanisms responsible for the dramatic emergence of Zika virus (ZIKV), accompanied by congenital Zika syndrome and Guillain-Barré syndrome (GBS), remain unclear. However, two hypotheses are prominent: (i) evolution for enhanced urban transmission via adaptation to mosquito vectors, or for enhanced human infection to increase amplification, or (ii) the stochastic introduction of ZIKV into large, naive human populations in regions with abundant Aedes aegypti populations, leading to enough rare, severe infection outcomes for their first recognition. Advances in animal models for human infection combined with improvements in serodiagnostics, better surveillance, and reverse genetic approaches should provide more conclusive evidence of whether mosquito transmission or human pathogenesis changed coincidentally with emergence in the South Pacific and the Americas. Ultimately, understanding the mechanisms of epidemic ZIKV emergence, and its associated syndromes, is critical to predict future risks as well as to target surveillance and control measures in key locations. PMID:28074023

  4. The epileptic spectrum in the congenital bilateral perisylvian syndrome. CBPS Multicenter Collaborative Study.

    PubMed

    Kuzniecky, R; Andermann, F; Guerrini, R

    1994-03-01

    We studied the frequency, clinical and EEG characteristics, and outcome of the epileptic syndrome in 31 patients with a congenital neurologic syndrome characterized by pseudobulbar palsy, cognitive deficits, and bilateral perisylvian polymicrogyria. Seizures were present in 27 of 31 patients (87%) and usually began between the ages of 4 and 12 years; they commonly consisted of atypical absence, atonic/tonic, and generalized tonic-clonic seizures. Partial attacks were present in 26%. EEG demonstrated generalized spike and wave abnormalities and, less frequently, multifocal discharges, predominantly in centro-parietal regions. Seizures were poorly controlled in 65%, with the remaining patients well controlled. Seven patients underwent callosotomy, which resulted in seizure improvement. This study indicates that the epileptic spectrum in this syndrome is broad but follows predictable patterns. Callosotomy is a valuable treatment strategy in those with intractable drop attacks.

  5. Microform holoprosencephaly with bilateral congenital elbow dislocation; increasing the phenotypic spectrum of Steinfeld syndrome.

    PubMed

    Jones, Gabriela E; Robertson, Lisa; Maniyar, Amit; Shammas, Christos; Phelan, Marie M; Vasudevan, Pradeep C; Tanteles, George A

    2016-03-01

    Steinfeld syndrome (MIM #184705) was first reported in 1982. It is characterised by holoprosencephaly and limb defects, however other anomalies may also be present. Following the initial description, three further cases have been reported in the literature. We report on a 23-year-old girl, with features of microform holoprosencephaly and bilateral congenital elbow dislocation in association with hypoplastic radial heads. She was identified to have a variant in the CDON gene inherited from her father who had ocular hypotelorism, but no other clinical features. We discuss the clinical features of Steinfeld syndrome, and broaden the phenotypic spectrum of this condition. Structural analysis suggests that this variant could lead to destabilisation of binding of CDON with hedgehog proteins. Further work needs to be done to confirm whether mutations in the CDON gene are the cause of Steinfeld syndrome.

  6. Inflammation and Rupture of a Congenital Pericardial Cyst Manifesting Itself as an Acute Chest Pain Syndrome

    PubMed Central

    Cheong, Benjamin Y.C.; Lufschanowski, Roberto

    2016-01-01

    We present the case of a 63-year-old woman with a remote history of supraventricular tachycardia and hyperlipidemia, who presented with recurrent episodes of acute-onset chest pain. An electrocardiogram showed no evidence of acute coronary syndrome. A chest radiograph revealed a prominent right-sided heart border. A suspected congenital pericardial cyst was identified on a computed tomographic chest scan, and stranding was noted around the cyst. The patient was treated with nonsteroidal anti-inflammatory drugs, and the pain initially abated. Another flare-up was treated similarly. Cardiac magnetic resonance imaging was then performed after symptoms had resolved, and no evidence of the cyst was seen. The suspected cause of the patient's chest pain was acute inflammation of a congenital pericardial cyst with subsequent rupture and resolution of symptoms. PMID:28100978

  7. Fragile X syndrome in two siblings with major congenital malformations

    SciTech Connect

    Giampietro, P.F.; Haas, B.R.; Lipper, E.

    1996-05-17

    We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2{1/2}, had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High-resolution chromosome analysis showed a 46,XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed. 24 refs., 4 figs.

  8. An unusual combination of congenital anomalies in an adult patient: patent ductus arteriosus, Kommerell's diverticulum with aberrant right subclavian artery, and heterotaxy syndrome.

    PubMed

    Celik, Murat; Celik, Turgay; Iyisoy, Atila; Guler, Adem

    2011-01-01

    The heterotaxy syndrome is a rare and sporadic disorder. This syndrome presents with situs ambiguus, splenic malformations such as asplenia or polysplenia, and congenital heart disease. Congenital heart diseases associated with this syndrome include a broad variety of manifestations. Patent ductus arteriosus is one of them and percutaneous transcatheter closure can be challenging in the setting of this syndrome. Kommerell's diverticulum is a saccular aneurysmal dilation at the origin of an aberrant subclavian artery, and can be related with other congenital anomalies. However, there is no previous report of Kommerell's diverticulum being found together with patent ductus arteriosus and heterotaxy syndrome.

  9. Clinical and molecular characterization of two patients with palmoplantar keratoderma-congenital alopecia syndrome type 2.

    PubMed

    Castori, M; Morlino, S; Sana, M E; Paradisi, M; Tadini, G; Angioni, A; Malacarne, M; Grammatico, P; Iascone, M; Forzano, F

    2016-08-01

    Palmoplantar keratoderma-congenital alopecia (PPKCA) syndrome is a rare genodermatosis, with two clinically recognizable forms: dominant (Type 1) and recessive (Type 2). Reports of only 18 patients have been published to date, and the molecular basis of the condition is unknown. We describe two cases with PPKCA Type 2 (PPKCA2), comprising a novel patient, originally reported as an example of autosomal ichthyosis follicularis-atrichia-photophobia syndrome, and the 6-year follow-up of a previously published case. Extensive molecular studies of both patients excluded mutations in all the known genes associated with PPK and partially overlapping syndromes. The striking similarities between these two patients confirm PPKCA2 as a discrete genodermatosis, of which the main features are congenital and universal alopecia, diffuse keratosis pilaris, facial erythema, and a specific PPK with predominant involvement of the fingertips and borders of the hands and feet, with evolution of sclerodactyly, contractures and constrictions. Clinical follow-up of these patients has demonstrated progressive worsening of the hand involvement and attenuation of facial erythema.

  10. Klippel-Feil syndrome associated with congenital cervical dislocation: report of an autopsy case.

    PubMed

    Shintaku, Masayuki; Wada, Kyosuke; Koyama, Takashi; Kohno, Hiroaki; Sakamoto, Takeshi; Hida, Shinya

    2013-01-01

    Klippel-Feil syndrome is an uncommon congenital anomaly that is characterized by abnormal fusion of the cervical vertebrae and occasionally accompanied by various anomalies of other bones and internal organs. We report the autopsy case of a 5-year-old girl with this syndrome ssociated with congenital cervical dislocation, with special reference to the pathological findings of the vertebral column and spinal cord. Principal anomalies of the cranio-spinal axis were as follows: partial defect of the clivus, scoliosis, hypoplasia of the whole cervical vertebrae, anterior dislocation of C7 with S-shaped deformity of the spinal canal, fusion of the spinous processes of the cervical and thoracic vertebrae, fusion of the vertebral bodies of C6 and C7 with collapse of C7, and spina bifida occulta of L5 and S1. In addition to these skeletal anomalies, subarachnoid vascular malformation in the medulla oblongata, a bronchogenic cyst in the posterior mediastinum, anomalous lobation of the lungs, and the mobile cecum were found at autopsy. The cervical cord showed an increase of the antero-posterior diameter, multifocal spongy changes of the white matter, and partial branching or duplication of the central canal. The brain showed features of anoxic encephalopathy. The partial defect of the clivus, C7 dislocation, and various lesions of the medulla oblongata and cervical cord were interpreted as integral components of, or lesions closely associated with, Klippel-Feil syndrome.

  11. Assisted reproductive technology and congenital overgrowth: some speculations on a case of Pallister-Killian syndrome.

    PubMed

    Chiurazzi, P; Bajer, J; Tabolacci, E; Pomponi, M G; Lecce, R; Zollino, M; Neri, G

    2004-10-15

    We report on a boy with Pallister-Killian syndrome (PKS) who was conceived by assisted reproductive technology (ART), specifically in vitro fertilization (IVF) with parents' gametes. A prenatal diagnosis performed elsewhere by CVS failed to detect the presence of the isochromosome 12p that was demonstrated postnatally in approximately 50% of cultured skin fibroblasts. Given that the patient did not show the congenital overgrowth typical of PKS, we speculate that ART might have restricted overgrowth in this particular case. More broadly, we hypothesize that overgrowth might protect from early demise fetuses conceived by ART, a technology known to cause low and very low birth weight.

  12. Congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes.

    PubMed

    Pavone, Piero; Praticò, Andrea D; Falsaperla, Raffaele; Ruggieri, Martino; Zollino, Marcella; Corsello, Giovanni; Neri, Giovanni

    2015-08-05

    Hypertrichosis is defined as an excessive growth in body hair beyond the normal variation compared with individuals of the same age, race and sex and affecting areas not predominantly androgen-dependent. The term hirsutism is usually referred to patients, mainly women, who show excessive hair growth with male pattern distribution.Hypertrichosis is classified according to age of onset (congenital or acquired), extent of distribution (generalized or circumscribed), site involved, and to whether the disorder is isolated or associated with other anomalies. Congenital hypertrichosis is rare and may be an isolated condition of the skin or a component feature of other disorders. Acquired hypertrichosis is more frequent and is secondary to a variety of causes including drug side effects, metabolic and endocrine disorders, cutaneous auto-inflammatory or infectious diseases, malnutrition and anorexia nervosa, and ovarian and adrenal neoplasms. In most cases, hypertrichosis is not an isolated symptom but is associated with other clinical signs including intellective delay, epilepsy or complex body malformations.A review of congenital generalized hypertrichosis is reported with particular attention given to the disorders where excessive diffuse body hair is a sign indicating the presence of complex malformation syndromes. The clinical course of a patient, previously described, with a 20-year follow-up is reported.

  13. Congenital Insensitivity to Pain and Anhydrosis (CIPA) Syndrome; A Report of 4 Cases

    PubMed Central

    Daneshjou, Khadije; Jafarieh, Hanieh; Raaeskarami, Seyed-Reza

    2012-01-01

    Background Background: Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by recurrent episodes of infections and unexplained fever, anhidrosis (inability to sweat), and absence of reaction to noxious stimuli, self-mutilating behavior, mental retardation and damages to oral structures. Case Presentation In this article, we have demonstrated the signs and symptoms of 4 children that refer to the pediatrics department of the Imam Khomeini hospital and assay about their complications with this disease. They mostly presented by recurrent osteomyelitis in their feet that severely controlled by antibiotic therapy and even surgery. They had no pain sensation in spite of deep sore and infection. Conclusion This syndrome can be diagnosed by clinical and paraclinical tests together but it would be better to confirm by genetic test. The diagnosis of this syndrome helps us to try for the better quality of life for the patients and avoid unnecessary amputations. PMID:23400697

  14. Child with Deletion 9p Syndrome Presenting with Craniofacial Dysmorphism, Developmental Delay, and Multiple Congenital Malformations

    PubMed Central

    Sirisena, Nirmala D.; Wijetunge, U. Kalpani S.; de Silva, Ramya; Dissanayake, Vajira H. W.

    2013-01-01

    A 4-month-old Sri Lankan male child case with a de novo terminal deletion in the p22→pter region of chromosome 9 is described. The child presented with craniofacial dysmorphism, developmental delay, and congenital malformations in agreement with the consensus phenotype. A distinctive feature observed in this child was complete collapse of the left lung due to malformation of lung tissue. Cytogenetic studies confirmed terminal deletion of the short arm of chromosome 9 distal to band p22 [46,XY,del(9)(p22→pter)]. This is the first reported case of a de novo deletion 9p syndrome associated with pulmonary hypoplasia. This finding contributes to the widening of the spectrum of phenotypic features associated with deletion 9p syndrome. PMID:23984121

  15. Congenital long QT syndrome: severe torsades de pointes provoked by epinephrine in a digenic mutation carrier.

    PubMed

    Tan, Vern Hsen; Duff, Henry; Kuriachan, Vikas; Gerull, Brenda

    2014-01-01

    Congenital Long QT Syndrome (LQTS) is a potentially lethal cardiac channelopathy characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram. The hallmark phenotypic features are syncope, seizure or sudden death, however most of the mutation carriers are asymptomatic and their risk for arrhythmias such as Torsade de pointes (TdP) are low. We report a case of Long QT syndrome with a corrected QT of 520 ms. For symptom - arrhythmia correlation a loop recorder was implanted with no documented arrhythmias. Epinephrine testing was performed for clinical risk stratification leading to Torsades de pointes during recovery phase which required defibrillation. Genetic testing discovered two pathogenic heterozygous mutations in two different LQT genes (SCN5A and KCNQ1). We propose a calcium homeostasis mechanism for the interaction of both mutations that exaggerated the phenotype, while each mutation by itself is causing a relatively modest phenotype.

  16. Muckle-Wells syndrome: a treatable cause of congenital sensorineural hearing loss.

    PubMed

    Stew, B T; Fishpool, S J C; Owens, D; Quine, S

    2013-01-01

    Muckle-Wells syndrome (MWS) is a rare autosomal dominant condition with variable expression. It is a subset of auto-inflammatory diseases characterised by recurrent inflammatory crises and is associated with chronic recurrent urticaria, sensorineural deafness, periodic arthritis and secondary amyloidosis. The diagnosis of MWS is a clinical one with sufferers classically presenting in childhood with a moderate fever and non-pruiginous urticaria. We describe a case of a six-year-old girl who was successfully diagnosed and treated with Anakinra. Muckle and Wells originally described this syndrome in 1962; however, only recently was it discovered to be genetically linked to chromosome 1q44 and subsequently to missense mutations in the CIAS1/NALP3/PYPAF1 gene. Since then, treatment has evolved and it remains one of few treatable causes of congenital profound sensorineural hearing loss.

  17. Bilateral agenesis of arcuate fasciculus demonstrated by fiber tractography in congenital bilateral perisylvian syndrome.

    PubMed

    Kilinc, Ozden; Ekinci, Gazanfer; Demirkol, Ezgi; Agan, Kadriye

    2015-03-01

    Congenital bilateral perisylvian syndrome (CBPS) is a type of cortical developmental abnormality associated with distinctive clinical and imaging features. Clinical spectrum of this syndrome is quite heterogeneous, with different degrees of neurological impairment in affected individuals. High-definition magnetic resonance imaging (MRI) has a great importance in revealing the presence of CBPS, but is limited in elucidating the heterogeneous clinical spectrum. The arcuate fasciculus (AF) is a prominent language tract in the perisylvian region interconnecting Broca and Wernicke areas, and has a high probability of being affected developmentally in CBPS. Herein, we report a case of CBPS with investigation of AF using diffusion tensor imaging (DTI) and fiber tractography in relation to clinical findings. We postulated that proven absence of AF on DTI and fiber tractography would correlate with a severe phenotype of CBPS.

  18. Severe Dumping Syndrome in a 6-year-old Girl with Congenital Microgastria Treated by Hunt-Lawrence Pouch

    PubMed Central

    Filisetti, Claudia; Maestri, Luciano; Meroni, Milena; Marinoni, Federica; Riccipetitoni, Giovanna

    2017-01-01

    Microgastria is a rare congenital condition often associated with other anomalies. In the present report we describe the case of a 6-year-old girl with isolated CM who presented with dumping syndrome successfully treated by a Hunt-Lawrence pouch. PMID:28361011

  19. Spigelian-cryptorchidism syndrome: a case report and discussion of the basic elements in a possibly new congenital syndrome.

    PubMed

    Rushfeldt, C; Oltmanns, G; Vonen, B

    2010-09-01

    Pediatric cases of Spigelian hernias are rare. Only a few reports on this condition, in combination with ipsilateral cryptorchidism and testis in the hernia sac, have been published. We report on Spigelian hernia in a 3-week-old boy containing both the ipsilateral testis, without a gubernaculum and an incarcerated loop of the small intestine. It has been suggested that the combination of Spigelian hernia and ipsilateral cryptorchidism is part of a new syndrome. We discuss whether the lack of a gubernaculum and an inguinal canal reported in other similar cases may be additional elements of this new syndrome. We present a comprehensive overview of pediatric patients with Spigelian-cryptorchidism syndrome reported in the English language literature. In 75% of male infants with Spigelian hernia, there is an associated ipsilateral cryptorchidism, and in 87% of these patients, the testis is found inside the hernia sac. Thus, the surgeon dealing with a congenital Spigelian hernia should look for an undescended testis and be prepared to find it in the hernia sac.

  20. Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome).

    PubMed

    Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika

    2016-12-01

    Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

  1. Ellis-van Creveld syndrome and congenital heart defects: presentation of an additional 32 cases.

    PubMed

    Hills, Christine B; Kochilas, Lazaros; Schimmenti, Lisa A; Moller, James H

    2011-10-01

    Ellis-van Creveld (EVC) syndrome is a rare genetic abnormality that has been linked to a mutation in the EVC or EVC2 genes. Common atrium (CA) is an uncommon cardiac malformation, and yet it is commonly found in patients with EVC. We performed a retrospective review of the cases submitted to the Pediatric Cardiac Care Consortium (PCCC) between 1982 and 2007. A review of the English-language literature for previously published cases, as well as current genetic research findings, was also performed. Thirty-two pediatric patients with congenital heart disease (CHD) and EVC syndrome were identified in the PCCC database. Twenty-eight (88%) had an endocardial cushion defect, with 15 of these having primary failure of atrial septation resulting in CA. Persistent left superior vena cava (LSVC) and pulmonary venous connection abnormalities were common. The incidence of persistent LSVC and pulmonary venous abnormalities were greater than previously reported for patients with EVC. Our study reviews the reported literature and adds 32 additional cases from the PCCC database. Review of the cardiac phenotype in patients with EVC syndrome reveals a characteristic pattern of atrioventricular canal defects with systemic and pulmonary venous abnormalities. The frequent association of these abnormalities is strongly reminiscent of the cardiac phenotype found in patients with heterotaxy syndromes. Emerging molecular and developmental studies suggest that EVC and EVC2 proteins may be important for cilia function, which is implicated in the pathogenesis of heterotaxy syndromes. It is speculated that coordinate function between the EVC proteins is required for a cilia-dependent cardiac morphogenesis.

  2. Congenital Cardiac, Aortic Arch, and Vascular Bed Anomalies in PHACE Syndrome (From The International PHACE Syndrome Registry)

    PubMed Central

    Bayer, Michelle L.; Frommelt, Peter C.; Blei, Francine; Breur, Johannes M.P.J.; Cordisco, Maria R.; Frieden, Ilona J.; Goddard, Deborah S.; Holland, Kristen E.; Krol, Alfons L.; Maheshwari, Mohit; Metry, Denise W.; Morel, Kimberly D.; North, Paula E.; Pope, Elena; Shieh, Joseph T.; Southern, James F.; Wargon, Orli; Siegel, Dawn H.; Drolet, Beth A.

    2014-01-01

    PHACE syndrome represents the association of large infantile hemangiomas of the head and neck with brain, cerebrovascular, cardiac, ocular, and ventral/midline defects. Cardiac and cerebrovascular anomalies are the most common extracutaneous features of PHACE, and they also constitute the greatest source of potential morbidity. Congenital heart disease in PHACE is incompletely described, and this study was conducted to better characterize its features. This study of the International PHACE Syndrome Registry represents the largest central review of clinical, radiology, and pathology data for cardiovascular anomalies in PHACE patients to date. 62/150 (41%) subjects had intracardiac, aortic arch, or brachiocephalic vessel anomalies. Aberrant origin of a subclavian artery was the most common cardiovascular anomaly (present in 31/150 (21%) of subjects). Coarctation was the second most common anomaly, identified in 28/150 (19%), and can be missed clinically in PHACE patients because of the frequent association of arch obstruction with aberrant subclavian origin. 23/62 (37%) subjects with cardiovascular anomalies required procedural intervention. A higher percentage of hemangiomas were located on the left side of the head/neck in patients with coarctation (46% vs. 39%); however, hemangioma distribution did not predict the presence of cardiovascular anomalies overall. In conclusion, PHACE is associated with a high risk of congenital heart disease. Cardiac and aortic arch imaging with detailed assessment of arch patency and brachiocephalic origins is essential for any patient suspected of having PHACE. Longitudinal investigation is needed to determine the long-term outcomes of cardiovascular anomalies in PHACE. PMID:24079520

  3. 14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype.

    PubMed

    Ellaway, Carolyn J; Ho, Gladys; Bettella, Elisa; Knapman, Alisa; Collins, Felicity; Hackett, Anna; McKenzie, Fiona; Darmanian, Artur; Peters, Gregory B; Fagan, Kerry; Christodoulou, John

    2013-05-01

    Rett syndrome is a clinically defined neurodevelopmental disorder almost exclusively affecting females. Usually sporadic, Rett syndrome is caused by mutations in the X-linked MECP2 gene in ∼90-95% of classic cases and 40-60% of individuals with atypical Rett syndrome. Mutations in the CDKL5 gene have been associated with the early-onset seizure variant of Rett syndrome and mutations in FOXG1 have been associated with the congenital Rett syndrome variant. We report the clinical features and array CGH findings of three atypical Rett syndrome patients who had severe intellectual impairment, early-onset developmental delay, postnatal microcephaly and hypotonia. In addition, the females had a seizure disorder, agenesis of the corpus callosum and subtle dysmorphism. All three were found to have an interstitial deletion of 14q12. The deleted region in common included the PRKD1 gene but not the FOXG1 gene. Gene expression analysis suggested a decrease in FOXG1 levels in two of the patients. Screening of 32 atypical Rett syndrome patients did not identify any pathogenic mutations in the PRKD1 gene, although a previously reported frameshift mutation affecting FOXG1 (c.256dupC, p.Gln86ProfsX35) was identified in a patient with the congenital Rett syndrome variant. There is phenotypic overlap between congenital Rett syndrome variants with FOXG1 mutations and the clinical presentation of our three patients with this 14q12 microdeletion, not encompassing the FOXG1 gene. We propose that the primary defect in these patients is misregulation of the FOXG1 gene rather than a primary abnormality of PRKD1.

  4. Further efforts in the achievement of congenital rubella syndrome/rubella elimination.

    PubMed

    Cozza, Vanessa; Martinelli, Domenico; Cappelli, Maria Giovanna; Tafuri, Silvio; Fortunato, Francesca; Prato, Rosa

    2015-01-01

    The Italian National Plan of Measles and Rubella Elimination 2010-2015 has deferred the objective to reduce congenital rubella syndrome (CRS) to <1 case per 100 000 live births to 2015 and has highlighted the need to reduce to <5% susceptibility to rubella among women in childbearing-age. In Puglia region, MMR vaccine coverage is 93% in newborns (cohort 2010; one dose), 85% in children 5-6 years old and 77% in adolescents (cohort 2005 and 1997, respectively; two doses). Combining available seroepidemiological data and results of a survey on the attitude towards rubella vaccination and rubella testing before pregnancy, we could estimate that 5.7% of Apulian women in childbearing-age are currently susceptible to rubella infection. The regional infectious disease routine notification system reported no cases of CRS and rubella in pregnancy in 2001-2010 period. The inconsistency among the mentioned data triggered the evaluation of the reliability of disease reporting. We performed a retrospective case-finding for the years 2003-2011. We scanned the regional hospital discharge registry to identify hospitalizations for rubella in pregnancy and CRS and retrieve individual records. We also searched for clinical history of CRS mothers in the delivery assistance certificate registry. We identified one CRS, two confirmed and four suspected congenital infections, and seven cases of rubella in pregnancy. Passive surveillance of CRS and rubella in pregnancy appears not to be reliable in the light of strengthening rubella elimination strategies.

  5. Rubella and Congenital Rubella Syndrome in the Philippines: A Systematic Review

    PubMed Central

    Fabay, Xenia Cathrine J.; Vinarao, Ariel B.; Manalastas, Ricardo

    2016-01-01

    Background. As part of regional elimination efforts, rubella-containing vaccines (RCV) have recently been introduced in the Philippines, yet the true burden of rubella and congenital rubella syndrome (CRS) in the country is largely unknown. Objective. To provide baseline information on rubella and CRS prior to routine vaccine introduction in the Philippines. Methods. We conducted a systematic literature review on rubella and CRS in the Philippines, including a cross-sectional study conducted in 2002 among 383 pregnant women attending the obstetric outpatient clinic of the Philippine General Hospital to assess rubella susceptibility of women of childbearing age. Results. 15 locally published and unpublished studies were reviewed. Susceptibility to rubella among women of childbearing age was higher in rural communities. Retrospective reviews revealed congenital heart diseases, cataracts, and hearing impairments to be most common presentations in children of CRS. In the cross-sectional study, 59 (15.4%) of the 383 pregnant women enrolled were seronegative for rubella IgG. Conclusion. Similar to other countries introducing RCV, it was only recently that surveillance for rubella has been established. Previous studies show substantial disabilities due to CRS and a substantial proportion of susceptible women who are at risk for having babies affected with CRS. Establishment of CRS surveillance and enhanced awareness on rubella case detection should be prioritized. PMID:28115948

  6. Identification of Ocular and Auditory Manifestations of Congenital Rubella Syndrome in Mbingo

    PubMed Central

    Rudnisky, Chris J.; Tambe, Emmanuel; Tipple, Graham; Tennant, Matthew T. S.

    2014-01-01

    Purpose. Congenital rubella syndrome (CRS) is a global cause of preventable hearing impairment, blindness, and intellectual impairment. The present study sought to identify ocular and auditory manifestations of CRS in school-aged children in Mbingo, Cameroon. Design. Cross sectional study. Subjects. Students at two schools, one for children with hearing impairment, were screened for cataract, congenital glaucoma, and pigmentary retinopathy. Methods. Students underwent seven-field digital fundus photography through a dilated pupil using a Topcon NW200 nonmydriatic camera. Images were assessed by retina specialists in Canada via teleophthalmology. Clinical evidence was integrated to form case definitions for CRS based on Center for Disease Control and Prevention guidelines. Serological evidence of rubella infection was obtained using standardized IgG antibody titers. Main Outcome Measure. Number of probable and suspicious cases of CRS. Results. Between September 2009 and May 2010, 320 students participated. There were 28 (10.2%) probable cases, 104 (37.8%) suspects, and 143 (52.0%) unaffected. Rubella IgG serology was positive in 79 (48.7%) of children with hearing impairment and 11 (7.4%) of children with normal hearing. Conclusions. The present study identified 28 probable cases of CRS. Furthermore, 92.6% of students with normal hearing did not possess rubella IgG antibodies making future cases of CRS likely without intervention. PMID:25525427

  7. Trauma due to Self-aggression in Patient with Waardenburg Syndrome associated with Congenital Anomalies.

    PubMed

    Marta, Sara Nader; Kawakami, Roberto Yoshio; Sgavioli, Claudia Almeida Prado Piccino; Correa, Ana Eliza; D'Árk de Oliveira El Kadre, Guaniara; Carvalho, Ricardo Sandri

    2016-08-01

    Waardenburg syndrome (WS) is an inherited autosomal dominant genetic disorder presenting variable penetrance and expressivity, with an estimated prevalence of 1:42,000. Clinical characteristics of WS include lateral displacement of the internal eye canthus, hyperplasia of the medial portion of the eyebrows, prominent and broad nasal base, congenital deafness, pigmentation of the iris and skin, and white forelock. A 24-year-old male patient, previously diagnosed with WS, was referred to the Special Needs Dental Clinic of Sacred Heart University, Bauru, Brazil. Parents reported that the patient was experiencing self-mutilation, particularly in the oral region. He presented multiple congenital anomalies, including anophthalmia, mental retardation, low-set ears, and leg deformities. Clinical oral examination revealed hypodontia, abnormalities in dental morphology, extensive dental caries, periodontal disease, and fistulae. Extensive scars on the tongue, lips, and hands caused by self-mutilation were also observed. In accordance with his family and neurologist, full-mouth extraction under general anesthesia was performed, especially considering his severe self-aggressive behavior and the necessity to be fed with soft-food diet due to his inability to chew. After the surgical procedure, a significant reduction in the patient's irritability and gain of weight were reported in the follow-ups of 30, 60, and 180 days.

  8. Congenital heart disease

    MedlinePlus

    ... defect - heartbeat Patent ductus arteriosis (PDA) - series References Fraser CD, Carberry KE. Congenital heart disease. In: Townsend ... ASD) Coarctation of the aorta Ellis-van Creveld syndrome Fetal alcohol syndrome Hypoplastic left heart syndrome Marfan ...

  9. WAGR syndrome and congenital hypothyroidism in a child with a Mosaic 11p13 deletion.

    PubMed

    Huynh, Minh Tuan; Boudry-Labis, Elise; Duban, Bénédicte; Andrieux, Joris; Tran, Cong Toai; Tampere, Heidi; Ceraso, Delphine; Manouvrier, Sylvie; Tachdjian, Gérard; Roche-Lestienne, Catherine; Vincent-Delorme, Catherine

    2017-04-11

    Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, a rare genetic disorder, is caused by the loss of 11p13 region including PAX6 and WT1. We report novel findings in a 28-month-old boy with aniridia, Wilm's tumor, congenital hypothyroidism, and sublingual thyroid ectopia. He was found to have a mosaic 5.28 Mb interstitial deletion of chromosome 11p13 deleting PAX6 and WT1. In order to clarify the mechanism underlying his thyroid dysgenesis, sequence analysis of candidate thyroid developmental genes was performed. We identified a FOXE1: c.532_537delGCCGCC p.(Ala178_Ala179del) variant that predisposes to thyroid ectopia. Taken together, this is the first report of mosaic 11p13 deletion in association with thyroid dysgenesis. We also propose a model of complex interactions of different genetic variants for this particular phenotype in the present patient.

  10. A new case of holoprosencephaly-polydactyly syndrome with alobar holoprosencephaly, preaxial polydactyly and congenital glaucoma.

    PubMed

    Sandal, G; Tok, L; Ormeci, A R

    2014-01-01

    We report a case of a female baby born at 34 weeks of gestation. Birth weight was 1760 g (10th-25th centile), length 41cm (10th-25th centile) and head circumference 27cm (< 10th centile). Clinical examination revealed microcephaly, hypotelorism, micrognathia, a flat rudimentary nose, high palate, thick dysplastic low-set ears, a short neck, preaxial polydactyly of the right hand, and overriding toes. Investigations showed bilateral congenital glaucoma, alobar holoprosencephaly, severe ventriculomegaly and absence midline structures of the brain, a large atrial septal defect. The karyotype was 46,XX. The case was also diagnosed as having holoprosencephaly-polydactyly syndrome (pseudotrisomy 13) because she had alobar holoprosencephaly, preaxial polydactyly, facial dysmorfism (hypotelorism, micrognathia, a flat rudimentary nose, high palate, thick dysplastic low-set ears) and normal karyotype.

  11. Genotype- and Phenotype-Guided Management of Congenital Long QT Syndrome

    PubMed Central

    Giudicessi, John R.; Ackerman, Michael J.

    2014-01-01

    Congenital Long QT syndrome (LQTS) is a genetically heterogeneous collection of heritable disorders of myocardial repolarization linked by their shared clinical phenotype of QT prolongation on electrocardiogram and an increased risk of potentially life-threatening cardiac arrhythmias. At the molecular level, mutations in 15 distinct LQTS-susceptibility genes that encode ion channel pore-forming α-subunits and accessory/auxiliary subunits central to the electromechanical function of the heart have been implicated in its pathogenesis. Over the past two decades, our evolving understanding of the electrophysiological mechanisms by which specific genetic substrates perturb the cardiac action potential has translated into vastly improved approaches to the diagnosis, risk stratification, and treatment of patients with LQTS. In this Review, we detail how our understanding of the molecular underpinnings of LQTS has yielded numerous clinically meaningful genotype-phenotype correlations and how these insights have translated into genotype- and phenotype-guided approaches to the clinical management of LQTS. PMID:24093767

  12. Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome.

    PubMed

    Goumy, Carole; Laffargue, Fanny; Eymard-Pierre, Eléonore; Kemeny, Stéphen; Gay-Bellile, Mathilde; Gouas, Laetiti; Gallot, Denis; Francannet, Christine; Tchirkov, Andrei; Pebrel-Richard, Céline; Vago, Philippe

    2015-01-01

    Microdeletions of 17q12 encompassing TCF2 are associated with maturity-onset of diabetes of the young type 5, cystic renal disease, pancreatic atrophy, Mullerian aplasia in females and variable cognitive impairment. We report on a patient with a de novo 17q12 microdeletion, 1.8 Mb in size, associated with congenital diaphragmatic hernia (CDH). The 5-year-old male patient presented multicystic renal dysplasia kidneys, minor facial dysmorphic features and skeletal anomalies, but neither developmental delay nor behavioral abnormalities. CDH has been previously associated with the 17q12 microdeletion syndrome only in one prenatal case. The present study reinforces the hypothesis that CDH is part of the phenotype for 17q12 microdeletion and that 17q12 encompasses candidate(s) gene(s) involved in diaphragm development. We suggest that PIGW, a gene involved in an early step of GPI biosynthesis, could be a strong candidate gene for CDH.

  13. Bilateral congenital lacrimal fistulas in an adult as part of ectrodactyly-ectodermal dysplasia-clefting syndrome: A rare anomaly.

    PubMed

    Ghosh, Debangshu; Saha, Somnath; Basu, Sumit Kumar

    2015-10-01

    Ectrodactyly-ectodermal dysplasia and clefting syndrome or "Lobster claw" deformity is a rare congenital anomaly that affects tissues of ectodermal and mesodermal origin. Nasolacrimal duct (NLD) obstruction with or without atresia of lacrimal passage is a common finding of such a syndrome. The authors report here even a rarer presentation of the syndrome which manifested as bilateral NLD obstruction and lacrimal fistula along with cleft lip and palate, syndactyly affecting all four limbs, mild mental retardation, otitis media, and sinusitis. Lacrimal duct obstruction and fistula were managed successfully with endoscopic dacryocystorhinostomy (DCR) which is a good alternative to lacrimal probing or open DCR in such a case.

  14. SCALP syndrome: sebaceous nevus syndrome, CNS malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis: a distinct syndromic entity.

    PubMed

    Lam, Joseph; Dohil, Magdalene A; Eichenfield, Lawrence F; Cunningham, Bari B

    2008-05-01

    Nevus sebaceus syndrome (SNS) is a constellation of nevus sebaceus with extracutaneous findings, including the ophthalmologic nervous, and musculoskeletal systems. Didymosis aplasticosebacea is a recently described entity consisting of aplasia cutis congenita and nevus sebaceus, implying twin spotting (didymosis). We describe a neonate with a nevus sebaceus on the scalp and a limbal dermoid on her left eye. Contiguous with the nevus sebaceus was a giant congenital melanocytic nevus and numerous areas of membranous aplasia cutis congenita. We propose the acronym SCALP (nevus sebaceus, central nervous system malformations, aplasia cutis congenita, limbal dermoid, pigmented nevus) to summarize the unique features of this case and review the two similar cases in the literature.

  15. Phakomatosis Pigmentovascularis Associated With Sturge–Weber Syndrome, Ota Nevus, and Congenital Glaucoma

    PubMed Central

    Yang, Yangfan; Guo, Xiujuan; Xu, Jiangang; Ye, Yiming; Liu, Xiaoan; Yu, Minbin

    2015-01-01

    Abstract Phakomatosis pigmentovascularis (PPV) is a rare congenital malformation syndrome that is characterized by a combination of capillary abnormalities and dermal melanocytosis. We describe 3 cases of PPV combined with bilateral Sturge–Weber syndrome (SWS), Ota nevus, and congenital glaucoma. Case 1 was a 2-year-old boy. Facial port-wine stains distributed along the 3 branches of his trigeminal nerves, which suggested the existence of SWS. Gray-blue patches were spread over the frontal and temporal areas of bilateral face, waist, buttocks, and thigh. Bilateral triangular alopecia was found on the temporal scalp. The diagnosis of Ota nevus was made by the bilateral scleral malanocystosis. Increased intraocular pressure, enlarged cornea, and pathologic optic disc cupping supported the diagnoses of infantile bilateral glaucoma. Case 2 was a 4-year-old boy. Port-wine stains were found on the face along the 3 branches of the trigeminal nerve and distributed along the trunk, arms, and legs. Mongolian spots spread over his frontal and temporal areas of the bilateral face, waist, buttocks, thigh, abdomen, and back. Infantile glaucoma was found in both eyes. Ota nevus were found in the both eyes. Optic coherent tomography (OCT) scans revealed increased thickness of choroid. Case 3 was a 5-year-old boy. Besides Ota nevus and infantile glaucoma in both eyes, color Doppler ultrasonography showed choroidal hemagioma. OCT scan showed increased choroidal thickness. The bilateral triangular alopecia on the child's temporal scalp was similar to that of Case 1. Cases 1 and 2 presented with port-wine stain patches that were consistent with the characteristic manifestation of PPV type IIb. However, the CMTC of Case 3 met the diagnostic criteria for PPV type Vb. Case 1 was treated with trabeculotomies in both eyes. For Cases 2 and 3, surgical interventions were not considered due to the high risks of antiglaucomatous operation complications. We prescribed them antiglaucoma

  16. Mutations in SPINT2 Cause a Syndromic Form of Congenital Sodium Diarrhea

    PubMed Central

    Heinz-Erian, Peter; Müller, Thomas; Krabichler, Birgit; Schranz, Melanie; Becker, Christian; Rüschendorf, Franz; Nürnberg, Peter; Rossier, Bernard; Vujic, Mihailo; Booth, Ian W.; Holmberg, Christer; Wijmenga, Cisca; Grigelioniene, Giedre; Kneepkens, C. M. Frank; Rosipal, Stefan; Mistrik, Martin; Kappler, Matthias; Michaud, Laurent; Dóczy, Ludwig-Christoph; Siu, Victoria Mok; Krantz, Marie; Zoller, Heinz; Utermann, Gerd; Janecke, Andreas R.

    2009-01-01

    Autosomal-recessive congenital sodium diarrhea (CSD) is characterized by perinatal onset of a persistent watery diarrhea with nonproportionally high fecal sodium excretion. Defective jejunal brush-border Na+/H+ exchange has been reported in three sporadic patients, but the molecular basis of the disease has not been elucidated. We reviewed data from a large cohort of CSD patients (n = 24) and distinguished CSD associated with choanal or anal atresia, hypertelorism, and corneal erosions—i.e., a syndromic form of CSD—occurring in ten families from an isolated form—i.e., classic CSD—presenting in seven families. Patients from both groups have a high risk of mortality due to immediate electrolyte imbalances and complications from long-term parenteral nutrition in the first years of life, but survivors can eventually adapt to partial or complete enteral nutrition. A genome-wide SNP scan was applied and identified a homozygous c.593−1G→A splicing mutation in SPINT2, encoding a Kunitz-type serine-protease inhibitor, in one extended kindred with syndromic CSD. The same mutation and four distinct, homozygous or compound heterozygous mutations (p.Y163C, c.1A→T, c.337+2T→C, c.553+2T→A) were identified in all syndromic patients. No SPINT2 mutations were found in classic-CSD patients. SPINT2 mutations were associated with loss of protein synthesis or failure to inhibit the serine protease trypsin in vitro. We delineate syndromic CSD as a distinct disease entity caused by SPINT2 loss-of-function mutations. SPINT2 mutations might lead to an excess of yet unknown serine protease activity in affected tissues. PMID:19185281

  17. Four systems involved with congenital abnormalities: a new type of syndromic hearing loss - ADOC Wang's syndrome?

    PubMed

    Wang, Qiuju; Zhao, Fei-Fan; Shi, Yong-Bing

    2011-10-01

    Syndromic hearing impairment encompasses hundreds of phenotypes. We identified a young female patient affected by the unique combination of dysplasia of the auricular system, patent ductus arteriosus (PDA), choroideremia, and enamel hypoplasia. The patient was treated with PDA ligature and left exploratory tympanotomy. Impairment in all four systems suggests a correlation with the neural crest. It is presumed that all of the features result from the same origin, probably through autosomal recessive inheritance or a novel mutation during the embryonic period. When audio-dento-oculo-cardio systems are involved, we suggest that this new syndrome can be named 'ADOC Wang's syndrome', summarizing the disorders of the four systems and indicative of the founding person (Dr Wang, the first and corresponding author of the paper).

  18. Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

    PubMed Central

    Mourato, Felipe Alves; Villachan, Lúcia Roberta R.; Mattos, Sandra da Silva

    2014-01-01

    OBJECTIVE: To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis. METHODS: Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7. RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age. CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension. PMID:25119745

  19. Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome in PMEL17 (Silver) mutant ponies: five cases

    PubMed Central

    Komáromy, András M.; Rowlan, Jessica S.; La Croix, Noelle C.; Mangan, Brendan G.

    2011-01-01

    Objective To describe the clinical phenotype and genetics of equine Multiple Congenital Ocular Anomalies (MCOA) syndrome in PMEL17 (Silver) mutant ponies. Animals studied Five presumably unrelated ponies. Procedures The ponies were examined under field conditions in their barn by slit lamp biomicroscopy, indirect ophthalmoscopy, and applanation tonometry. Blood was collected and genomic DNA extracted for MCOA genotyping using the PMEL17ex11 marker. Results One pony solely presented with temporal ciliary body cysts, suggestive of the less severe Cyst phenotype of MCOA; the animal was heterozygous at the MCOA locus. Multiple bilateral anterior segment anomalies were identified in four ponies, consistent with the more severe MCOA phenotype characterized by cornea globosa, iris hypoplasia, encircling granula iridica along the pupillary ruff, and cataracts. These animals were homozygous for the mutant MCOA allele. Four of the ponies had a silver dapple or chocolate coat color with white or flaxen manes and tails. Silver dappling was masked by the palomino coloring of a 5th pony that was homozygous at the MCOA locus. Conclusions The MCOA syndrome can be seen in ponies. The results of both clinical evaluation and genotyping resembled the previously described MCOA of both Rocky Mountain and Kentucky Mountain Saddle horses. PMID:21929608

  20. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

    PubMed

    Sifrim, Alejandro; Hitz, Marc-Phillip; Wilsdon, Anna; Breckpot, Jeroen; Turki, Saeed H Al; Thienpont, Bernard; McRae, Jeremy; Fitzgerald, Tomas W; Singh, Tarjinder; Swaminathan, Ganesh Jawahar; Prigmore, Elena; Rajan, Diana; Abdul-Khaliq, Hashim; Banka, Siddharth; Bauer, Ulrike M M; Bentham, Jamie; Berger, Felix; Bhattacharya, Shoumo; Bu'Lock, Frances; Canham, Natalie; Colgiu, Irina-Gabriela; Cosgrove, Catherine; Cox, Helen; Daehnert, Ingo; Daly, Allan; Danesh, John; Fryer, Alan; Gewillig, Marc; Hobson, Emma; Hoff, Kirstin; Homfray, Tessa; Kahlert, Anne-Karin; Ketley, Ami; Kramer, Hans-Heiner; Lachlan, Katherine; Lampe, Anne Katrin; Louw, Jacoba J; Manickara, Ashok Kumar; Manase, Dorin; McCarthy, Karen P; Metcalfe, Kay; Moore, Carmel; Newbury-Ecob, Ruth; Omer, Seham Osman; Ouwehand, Willem H; Park, Soo-Mi; Parker, Michael J; Pickardt, Thomas; Pollard, Martin O; Robert, Leema; Roberts, David J; Sambrook, Jennifer; Setchfield, Kerry; Stiller, Brigitte; Thornborough, Chris; Toka, Okan; Watkins, Hugh; Williams, Denise; Wright, Michael; Mital, Seema; Daubeney, Piers E F; Keavney, Bernard; Goodship, Judith; Abu-Sulaiman, Riyadh Mahdi; Klaassen, Sabine; Wright, Caroline F; Firth, Helen V; Barrett, Jeffrey C; Devriendt, Koenraad; FitzPatrick, David R; Brook, J David; Hurles, Matthew E

    2016-09-01

    Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.

  1. Congenital long QT syndrome with compound mutations in the KCNH2 gene.

    PubMed

    Bando, Sachiko; Soeki, Takeshi; Matsuura, Tomomi; Niki, Toshiyuki; Ise, Takayuki; Yamaguchi, Koji; Taketani, Yoshio; Iwase, Takashi; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Akaike, Masashi; Aiba, Takeshi; Shimizu, Wataru; Sata, Masataka

    2014-07-01

    Congenital long QT syndrome is a genetic disorder encompassing a family of mutations that can lead to aberrant ventricular electrical activity. We report on two brothers with long QT syndrome caused by compound mutations in the KCNH2 gene inherited from parents who had no prolonged QT interval on electrocardiography. The proband had syncope, and his elder brother suffered from ventricular fibrillation. Genetic testing revealed that both brothers had multiple mutations in the KCNH2 gene, including a missense mutation of C1474T (exon 6) as well as a frameshift/nonsense mutation, resulting from the insertion of 25 nucleotides, which caused an altered amino acid sequence beginning at codon 302 and a premature termination codon (i.e., TAG) at codon 339 (exon 4). Family genetic screening found that their father had the same frameshift mutation, and their mother and sister had the same missense mutation, in the KCNH2 gene. However, these other family members were asymptomatic, with normal QT intervals on electrocardiography. These results suggest that compound mutations in the KCNH2 gene inherited independently from the parents made the phenotypes of their sons more severe.

  2. Congenital heart disease and Down syndrome: various aspects of a confirmed association

    PubMed Central

    Sanaa, Benhaourech,; Abdenasser, Drighil,; Ayoub, El Hammiri

    2016-01-01

    Summary Background Congenital heart disease (CHD) is frequently described in patients with Down syndrome (DS) and is the main cause of death in this population during the first two years of life. The spectrum of CHD patterns in DS varies widely worldwide; this variation could be due to sociodemographic, genetic and geographic factors. Methods A six-year retrospective, descriptive study was carried out from December 2008 to October 2014, based on the Paediatric Unit CHD registry of Ibn Rochd University Hospital. Clinical, echocardiographic and outcomes data were collected and sorted according to confirmation of the syndrome. Results Among 2 156 patients with CHD, 128 were identified with Down syndrome. The genders were equally represented (gender ratio 1) and the median age at diagnosis was 9.5 months (2 days to 16 years). The median age of mothers at delivery was 39 years (16–47). Of the 186 CHD lesions reported, the most common was atrioventricular septal defect (AVSD, 29%), followed by ventricular septal defect (VSD,21.5%) and atrial septal defect (ASD, 19.9%). The most common associations of CHD were AVSD + ASD (10%) and VSD + ASD (7.8%). Surgery was the most common modality of treatment (54.3%). The overall mortality rate was 14.1%. Conclusion Our study confirmed that the profile and type of CHD in DS in the Moroccan setting exhibited slight differences in the distribution of these CHDs compared with European neighbours and other Western countries. Further studies are needed to determine which variables have an impact on these differences. PMID:27805241

  3. Global Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination - 2000-2014.

    PubMed

    Grant, Gavin B; Reef, Susan E; Dabbagh, Alya; Gacic-Dobo, Marta; Strebel, Peter M

    2015-09-25

    Rubella virus usually causes a mild fever and rash in children and adults. However, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national routine immunization schedules, including an initial vaccination campaign usually targeting children aged 9 months-15 years . The Global Vaccine Action Plan endorsed by the World Health Assembly in 2012 and the Global Measles and Rubella Strategic Plan (2012-2020) published by Measles and Rubella Initiative partners in 2012 both include goals to eliminate rubella and CRS in at least two WHO regions by 2015, and at least five WHO regions by 2020 (2,3). This report updates a previous report and summarizes global progress toward rubella and CRS control and elimination during 2000-2014. As of December 2014, RCV had been introduced in 140 (72%) countries, an increase from 99 (51%) countries in 2000 (for this report, WHO member states are referred to as countries). Reported rubella cases declined 95%, from 670,894 cases in 102 countries in 2000 to 33,068 cases in 162 countries in 2014, although reporting is inconsistent. To achieve the 2020 Global Vaccine Action Plan rubella and CRS elimination goals, RCV introduction needs to continue as country criteria indicating readiness are met, and rubella and CRS surveillance need to be strengthened to ensure that progress toward elimination can be measured.

  4. A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma

    PubMed Central

    Micheal, Shazia; Villanueva-Mendoza, Cristina; Cortés-González, Vianney; Khan, Muhammad Imran; den Hollander, Anneke I.

    2016-01-01

    Background Anterior segment dysgenesis (ASD) disorders are a group of clinically and genetically heterogeneous phenotypes in which frequently cornea, iris, and lens are affected. This study aimed to identify novel mutations in PAX6, PITX2 and FOXC1 in families with anterior segment dysgenesis disorders. Methods We studied 14 Pakistani and one Mexican family with Axenfeld Rieger syndrome (ARS; n = 10) or aniridia (n = 5). All affected and unaffected family members underwent full ophthalmologic and general examinations. Total genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the FOXC1, PAX6, and PITX2 genes. Results Mutations were identified in five of the 15 probands; four variants were novel and one variant was described previously. A novel de novo variant (c.225C>A; p.Tyr75*) was identified in the PAX6 gene in two unrelated probands with aniridia. In addition, a known variant (c.649C>T; p.Arg217*) in PAX6 segregated in a family with aniridia. In the FOXC1 gene, a novel heterozygous variant (c.454T>C; p.Trp152Arg) segregated with the disease in a Mexican family with ARS. A novel homozygous variant (c.92_100del; p.Ala31_Ala33del) in the FOXC1 gene segregated in a Pakistani family with ARS and congenital glaucoma. Conclusions Our study expands the mutation spectrum of the PAX6 and FOXC1 genes in individuals with anterior segment dysgenesis disorders. In addition, our study suggests that FOXC1 mutations, besides typical autosomal dominant ARS, can also cause ARS with congenital glaucoma through an autosomal recessive inheritance pattern. Our results thus expand the disease spectrum of FOXC1, and may lead to a better understanding of the role of FOXC1 in development. PMID:27463523

  5. Endothelin receptor antagonists improve exercise tolerance and oxygen saturations in patients with Eisenmenger syndrome and congenital heart defects.

    PubMed

    Mehta, Puja K; Simpson, Leo; Lee, Eva K; Lyle, Teresa A; McConnell, Michael E; Book, Wendy M

    2008-01-01

    Patients with Eisenmenger syndrome experience substantial morbidity and decreased survival rates. In advanced cases, lung transplantation with cardiac repair or heart-lung transplantation is often the only option. The efficacy of endothelin receptor antagonists in Eisenmenger syndrome, which has similar pathophysiology to idiopathic pulmonary hypertension, remains unknown.We retrospectively studied adults with congenital heart disease and Eisenmenger syndrome who were treated with endothelin receptor antagonists. Analysis included chart reviews of clinical evaluations, oxygen saturation levels, functional class, 6-minute walk distances, and pulmonary artery pressures. In the 24 patients studied, Eisenmenger syndrome was caused by ventricular septal defect (6 patients), atrial septal defect (5), atrioventricular canal defect (3), complex congenital heart disease (9), and patent ductus arteriosus (1).Eisenmenger syndrome was treated with bosentan (21 patients) and sitaxsentan (3 patients). On average, therapy lasted 19 +/- 12 months. Subsequently, mean 6-minute walk distances improved from 226 +/- 159 m to 351 +/- 113 m (P = 0.004), and World Health Organization functional class improved > or =1 grade (P < 0.0001). Oxygen saturations increased on therapy from 80.5% to 87% (P < 0.0001). Pulmonary arterial systolic pressures decreased from 97 +/- 21 mmHg to 78 +/- 27 mmHg, and mean pressures from 59 +/- 16 mmHg to 47 +/- 17 mmHg (both P < 0.0001). Neither major complications from therapy nor changes in pulmonary capillary wedge pressure occurred.Endothelin receptor antagonists may play an important role in improving 6-minute walk distance, oxygen saturation, pulmonary artery pressures, and symptoms in adults who have congenital heart defects and Eisenmenger syndrome.

  6. Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children: The PodoNet Registry Cohort

    PubMed Central

    Trautmann, Agnes; Bodria, Monica; Ozaltin, Fatih; Gheisari, Alaleh; Melk, Anette; Azocar, Marta; Anarat, Ali; Caliskan, Salim; Emma, Francesco; Gellermann, Jutta; Oh, Jun; Baskin, Esra; Ksiazek, Joanna; Remuzzi, Giuseppe; Erdogan, Ozlem; Akman, Sema; Dusek, Jiri; Davitaia, Tinatin; Özkaya, Ozan; Papachristou, Fotios; Firszt-Adamczyk, Agnieszka; Urasinski, Tomasz; Testa, Sara; Krmar, Rafael T.; Hyla-Klekot, Lidia; Pasini, Andrea; Özcakar, Z. Birsin; Sallay, Peter; Cakar, Nilgun; Galanti, Monica; Terzic, Joelle; Aoun, Bilal; Caldas Afonso, Alberto; Szymanik-Grzelak, Hanna; Lipska, Beata S.; Schnaidt, Sven

    2015-01-01

    Background and objectives Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. Design, setting, participants, & measurements Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. Results Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%–16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%–45% of patients

  7. Craniosynostosis, ectopia lentis, and congenital heart defects: further delineation of an autosomal dominant syndrome with incomplete penetrance.

    PubMed

    Quercia, Nada L; Teebi, Ahmad S

    2002-01-01

    The association of craniosynostosis with ectopia lentis is extremely rare. This was recently reported in monozygotic twin sisters, supporting a genetic etiology for this syndromic association. We report on female first cousins once removed who were born with unilateral coronal synostosis. One cousin also had peripheral pulmonic branch stenosis at birth and was later found to have ectopia lentis and severe myopia. The other cousin had an atrial septal defect, mitral valve prolapse, and only mild myopia. Their intelligence is normal. The inheritance is likely autosomal dominant with variable expression and incomplete penetrance and further defines this syndrome to include congenital heart defects. These findings will have important implications for genetic counseling.

  8. Crisis resource management of the airway in a patient with Klippel-Feil syndrome, congenital deafness, and aortic dissection.

    PubMed

    Khawaja, Omar M; Reed, J Taylor; Shaefi, Shahzad; Chitilian, Hovig V; Sandberg, Warren S

    2009-04-01

    Klippel-Feil syndrome is a visually arresting deformity wherein severe restriction of cervical motion predicts a difficult airway. Even minor distraction of the neck risks cervical spine or neurologic injury, so regional techniques, awake fiberoptic intubation, or awake tracheostomy are recommended anesthetic approaches. We present a case of aortic dissection in a Klippel-Feil syndrome patient for whom congenital bilateral deafness, coupled with the urgency of the surgery, mitigated against the recommended first-choice techniques. Using anesthesia crisis resource management methods, a multi-member team rehearsed predefined roles and then managed the airway via inhaled induction of anesthesia, followed by flexible fiberoptic intubation.

  9. Congenital generalized hypertrichosis terminalis: a proposed classification and a plea to avoid the ambiguous term "Ambras syndrome".

    PubMed

    Chen, WenChieh; Ring, Johannes; Happle, Rudolf

    2015-01-01

    Congenital generalized hypertrichosis terminalis (CGHT) is a heterogenous group of diseases with continuing excessive growth of terminal hair. "Ambras syndrome" was first coined by Baumeister in 1993 to describe a case of nonsyndromic CGHT which was erroneously analogized to the portrait paintings of Petrus Gonzales and his children, exhibited in Ambras Castle near Innsbruck, Austria. This family probably, a syndromic type with abnormal dentition, inherited as an autosomal dominant trait. CGHT associated with gingival hyperplasia is probably a particular entity typified by the historical cases of Julia Pastrana and her son. An X-linked type of CGHT has likewise been categorized as "Ambras syndrome". Moreover, some reports have mistakenly classified "Ambras syndrome" as an example of hypertrichosis lanuginosa. Potential gene loci identified so far may include 8q22, 17q24.2-q24.3 and Xq24-q27.1. The designation "Ambras syndrome" has thus been applied to various types of congenital hypertrichosis that differ to such degree that the name "Ambras" has no specific meaning, neither in the past nor in the future. Hence, this misleading term should now be jettisoned.

  10. Acute Inhibition of MEK Suppresses Congenital Melanocytic Nevus Syndrome in a Murine Model Driven by Activated NRAS and Wnt Signaling.

    PubMed

    Pawlikowski, Jeffrey S; Brock, Claire; Chen, Sheau-Chiann; Al-Olabi, Lara; Nixon, Colin; McGregor, Fiona; Paine, Simon; Chanudet, Estelle; Lambie, Wendy; Holmes, William M; Mullin, James M; Richmond, Ann; Wu, Hong; Blyth, Karen; King, Ayala; Kinsler, Veronica A; Adams, Peter D

    2015-08-01

    Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRAS(Q61K) and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition.

  11. Myasthenic crisis and polymyositis induced by one dose of nivolumab.

    PubMed

    Kimura, Toshihiro; Fukushima, Satoshi; Miyashita, Azusa; Aoi, Jun; Jinnin, Masatoshi; Kosaka, Takayuki; Ando, Yukio; Matsukawa, Masakazu; Inoue, Hiroyuki; Kiyotani, Kazuma; Park, Jae-Hyun; Nakamura, Yusuke; Ihn, Hironobu

    2016-07-01

    An 80-year-old man, who developed multiple lymph node and skin metastasis of malignant melanoma, received nivolumab monotherapy. Two weeks after the first dose, he experienced anorexia and fatigue, and suffered from progressive, severe dyspnea and muscle weakness. We diagnosed him with myocarditis, myositis, and myasthenic crisis induced by nivolumab. We commenced steroid therapy, immune absorption therapy, plasma exchange therapy, and i.v. immunoglobulin therapy, and succeeded in saving his life. Because his serum level of anti-acetylcholine receptor antibodies in a sample collected before nivolumab treatment were positive and were elevated significantly after nivolumab, we suspected that nivolumab triggered a severe autoimmune response, which progressed subclinical myasthenia gravis to myasthenic crisis. We carried out T cell receptor repertoire analysis using next-generation sequencing technologies and identified infiltration of clonally expanded T cell populations in the skeletal muscle after nivolumab treatment, implying a very strong T cell immune response against muscular cells. To avoid severe immune-related adverse events, the exclusion of patients with subclinical autoimmune disease is very important for treatment with immune checkpoint inhibitors.

  12. Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review

    PubMed Central

    Sandoval, Renata Lazari; Zaconeta, Carlos Moreno; Margotto, Paulo Roberto; Cardoso, Maria Teresinha de Oliveira; França, Evely Mirella Santos; Medina, Cristina Touguinha Neves; Canó, Talyta Matos; de Faria, Aline Saliba

    2016-01-01

    Abstract Objective: To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. Case description: Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. Comments: This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism. PMID:26838603

  13. Rubella in the Russian Federation: epidemiological features and control measures to prevent the congenital rubella syndrome.

    PubMed Central

    Semerikov, V. V.; Lavrentyeva, I. N.; Popov, V. F.; Fletcher, M. A.; Kolotov, M. E.

    2000-01-01

    A review of the epidemiology of clinical rubella in the Perm region of the Russian Federation from 1979-97 showed that the incidence was about 220 cases per 100,000 population. Congenital rubella syndrome (CRS) accounted for 15% of birth defects and for about 3.5 cases of CRS per 1000 live births per year. Surveys of the seroepidemiology of rubella infection revealed that the susceptibility rate among pregnant women (i.e. rubella virus antibody haemagglutination-inhibition (HAI) assay titres < 10) was 16.5%. As serum rubella antibody HAI titres > or = 10 both prevented infection in pregnant women and protected their foetuses, serological testing has been introduced into the routine antenatal services. Pre-existing rubella antibodies were found not to interfere with the immune response to vaccination, so selective immunization was provided to girls approaching puberty and to women of childbearing age. A programme of epidemiological surveillance is being developed to define tactics for the widescale introduction of rubella vaccination. PMID:11117959

  14. Prevalence of congenital heart defects associated with Down syndrome in Korea.

    PubMed

    Kim, Min-A; Lee, You Sun; Yee, Nan Hee; Choi, Jeong Soo; Choi, Jung Yun; Seo, Kyung

    2014-11-01

    Congenital heart defect (CHD) is common in infants with Down syndrome (DS), which is the principle cause of mortality. However, there is no data available for the frequency and types of CHD in infants with DS in Korea. We investigated the frequency of CHD in infants with DS in Korea. After the survey on birth defects was conducted throughout the country, the prevalence of CHD in DS in 2005-2006 was calculated. This study was conducted based on the medical insurance claims database of the National Health Insurance Corporation. The number of total births in Korea was 888,263 in 2005-2006; of them, 25,975 cases of birth defects were identified. The prevalence of DS was 4.4 per 10,000 total births, accounting for 1.5% of all birth defects. Of the 394 infants with DS, 224 (56.9%) had a CHD. Atrial septal defect was the most common defect accounting for 30.5% of DS followed by ventricular septal defect (19.3%), patent duct arteriosus (17.5%), and atrioventricular septal defect (9.4%). Our study will be helpful to demonstrate the current status of DS and to identify the distribution of CHD in infants with DS in Korea.

  15. Sevoflurane-associated torsade de pointes in a patient with congenital long QT syndrome genotype 2.

    PubMed

    Kumakura, Mika; Hara, Koji; Sata, Takeyoshi

    2016-09-01

    Although patients with congenital long QT syndrome (c-LQTS) are considered to be at high risk for anesthesia, few reports describe c-LQTS genotype-specific considerations for anesthesia. We describe a case of torsade de pointes (TdP) caused by sevoflurane in a patient with c-LQTS genotype 2 (LQT2). A 39-year-old woman diagnosed with c-LQTS was scheduled for an elective therapeutic abortion. Immediately after starting the operation, the patient developed TdP. Since pulseless ventricular tachycardia was sustained despite intravenous injection of lidocaine, defibrillation was performed. Analysis of the electrocardiogram revealed that the corrected QT interval before anesthesia was 530 ms and 2.0% sevoflurane markedly prolonged the corrected QT interval to 693 ms. Postoperative studies revealed a mutation in the KCNH2 gene. Anesthesiologists should note that patients with LQT2 could be more susceptible to volatile anesthetics than are those with other major genotypes. Genotype-specific management of anesthesia may reduce the risk of developing TdP during the perioperative period.

  16. Genetic dissection of Down syndrome-associated congenital heart defects using a new mouse mapping panel

    PubMed Central

    Lana-Elola, Eva; Watson-Scales, Sheona; Slender, Amy; Gibbins, Dorota; Martineau, Alexandrine; Douglas, Charlotte; Mohun, Timothy; Fisher, Elizabeth MC; Tybulewicz, Victor LJ

    2016-01-01

    Down syndrome (DS), caused by trisomy of human chromosome 21 (Hsa21), is the most common cause of congenital heart defects (CHD), yet the genetic and mechanistic causes of these defects remain unknown. To identify dosage-sensitive genes that cause DS phenotypes, including CHD, we used chromosome engineering to generate a mapping panel of 7 mouse strains with partial trisomies of regions of mouse chromosome 16 orthologous to Hsa21. Using high-resolution episcopic microscopy and three-dimensional modeling we show that these strains accurately model DS CHD. Systematic analysis of the 7 strains identified a minimal critical region sufficient to cause CHD when present in 3 copies, and showed that it contained at least two dosage-sensitive loci. Furthermore, two of these new strains model a specific subtype of atrio-ventricular septal defects with exclusive ventricular shunting and demonstrate that, contrary to current hypotheses, these CHD are not due to failure in formation of the dorsal mesenchymal protrusion. DOI: http://dx.doi.org/10.7554/eLife.11614.001 PMID:26765563

  17. Pulmonary hypertension in adults with congenital heart disease and Eisenmenger syndrome: current advanced management strategies.

    PubMed

    D'Alto, Michele; Diller, Gerhard-Paul

    2014-09-01

    The presence of pulmonary arterial hypertension (PAH) increases morbidity and reduces survival in patients with congenital heart disease (CHD). PAH-CHD is a heterogeneous condition, depending on the type of the underlying defect and previous repair strategies. There is growing evidence of the benefits of PAH-specific therapy in the PAH-CHD population, but despite recent advances mortality rates remain relatively high. In the last years, an increasing focus has been placed on patients with PAH-CHD and net left-to-right shunt. Currently, there are limited data to guide the management of these patients and uncertainty on the cut-off values for eventual defect closure. Pregnancy conveys significant risks in PAH-CHD patients: appropriate counselling and care, including psychological support and a multidisciplinary team, should be part of the routine management of women with PAH-CHD of reproductive age. Some subgroups, such as patients with Down's syndrome, Fontan circulation and 'segmental' pulmonary hypertension, present particular challenges in terms of management and therapy. The current review focuses on contemporary treatment strategies in PAH-CHD patients with particular emphasis on challenging patient groups and conditions.

  18. Cognitive Impairment and Brain Imaging Characteristics of Patients with Congenital Cataracts, Facial Dysmorphism, Neuropathy Syndrome.

    PubMed

    Chamova, Teodora; Zlatareva, Dora; Raycheva, Margarita; Bichev, Stoyan; Kalaydjieva, Luba; Tournev, Ivailo

    2015-01-01

    Congenital cataracts, facial dysmorphism, neuropathy (CCFDN) syndrome is a complex autosomal recessive multisystem disorder. The aim of the current study is to evaluate the degree of cognitive impairment in a cohort of 22 CCFDN patients and its correlation with patients' age, motor disability, ataxia, and neuroimaging changes. Twenty-two patients with genetically confirmed diagnosis of CCFDN underwent a detailed neurological examination. Verbal and nonverbal intelligence, memory, executive functions, and verbal fluency wеre assessed in all the patients aged 4 to 47 years. Brain magnetic resonance imaging was performed in 20 affected patients. Eighteen affected were classified as having mild intellectual deficit, whereas 4 had borderline intelligence. In all psychometric tests, evaluating different cognitive domains, CCFDN patients had statistically significant lower scores when compared to the healthy control group. All cognitive domains seemed equally affected. The main abnormalities on brain MRI found in 19/20 patients included diffuse cerebral atrophy, enlargement of the lateral ventricles, and focal lesions in the subcortical white matter, different in number and size, consistent with demyelination more pronounced in the older CCFDN patients. The correlation analysis of the structural brain changes and the cognitive impairment found a statistically significant correlation only between the impairment of short-term verbal memory and the MRI changes.

  19. Pulmonary Arterial Hypertension Associated with Congenital Heart Disease and Eisenmenger Syndrome: Current Practice in Pediatrics

    PubMed Central

    Frank, David B.; Hanna, Brian D.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an uncommon but serious disease characterized by severe pulmonary vascular disease and significant morbidity and mortality. PAH associated with congenital heart disease (APAH-CHD) is one etiology of PAH that has innate characteristics delineating it from other forms of PAH. The patient with APAH-CHD presents with unique challenges consisting of not only pulmonary vascular disease but also the complexity of the cardiac lesion. Eisenmenger syndrome (ES) represents the severe end of the spectrum for disease in APAH-CHD. Over time, systemic-to-pulmonary shunting through cardiac defects increases pulmonary vascular resistance to levels significant enough to reverse shunting across the defect. Historically, ES patients have been reported to have better outcomes than IPAH despite similarities in pulmonary vascular disease. However, recent studies are challenging this notion. Nonetheless, APAH-CHD survival has improved with the advent of modern PAH targeted therapies. New therapeutic options have allowed us to reconsider the dogma of inoperability in APAH-CHD patients with unrepaired defects. Certainly advances have been made, however, investigators must continue to advance the field through controlled clinical trials in both adult and pediatric APAH-CHD patients. PMID:25604592

  20. A novel syndrome of abnormal striatum and congenital cataract: evidence for linkage to chromosomes 11.

    PubMed

    Al-Owain, M; Al-Zahrani, J; Al-Bakheet, A; Abudheim, N; Al-Younes, B; Aldhalaan, H; Al-Zaidan, H; Colak, D; Almohaileb, F; Abouzied, M E; Al-Fadhli, F; Meyer, B; Kaya, N

    2013-09-01

    We report a consanguineous family of three girls and one boy affected with a novel syndrome involving the lens and the basal ganglia. The phenotype is strikingly similar between affected siblings with cognitive impairment, attention deficit hyperactivity disorder (ADHD), microcephaly, growth retardation, congenital cataract, and dystonia. The magnetic resonance imaging showed unusual pattern of swelling of the caudate heads and thinning of the putamina with severe degree of hypometabolism on the [18F] deoxyglucose positron emission tomography. Furthermore, the clinical assessment provides the evidence that the neurological phenotype is very slowly progressive. We utilized the 10K single-nucleotide polymorphism (SNP) microarray genotyping for linkage analysis. Genome-wide scan indicated a 45.9-Mb region with a 4.2353 logarithm of the odds score on chromosome 11. Affymetrix genome-wide human SNP array 6.0 assay did not show any gross chromosomal abnormality. Targeted sequencing of two candidate genes within the linkage interval (PAX6 and B3GALTL) as well as mtDNA genome sequencing did not reveal any putative mutations.

  1. Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells

    PubMed Central

    Fontes-Oliveira, Cibely C.; Steinz, Maarten; Schneiderat, Peter; Mulder, Hindrik; Durbeej, Madeleine

    2017-01-01

    Skeletal muscle has high energy requirement and alterations in metabolism are associated with pathological conditions causing muscle wasting and impaired regeneration. Congenital muscular dystrophy type 1A (MDC1A) is a severe muscle disorder caused by mutations in the LAMA2 gene. Leigh syndrome (LS) is a neurometabolic disease caused by mutations in genes related to mitochondrial function. Skeletal muscle is severely affected in both diseases and a common feature is muscle weakness that leads to hypotonia and respiratory problems. Here, we have investigated the bioenergetic profile in myogenic cells from MDC1A and LS patients. We found dysregulated expression of genes related to energy production, apoptosis and proteasome in myoblasts and myotubes. Moreover, impaired mitochondrial function and a compensatory upregulation of glycolysis were observed when monitored in real-time. Also, alterations in cell cycle populations in myoblasts and enhanced caspase-3 activity in myotubes were observed. Thus, we have for the first time demonstrated an impairment of the bioenergetic status in human MDC1A and LS muscle cells, which could contribute to cell cycle disturbance and increased apoptosis. Our findings suggest that skeletal muscle metabolism might be a promising pharmacological target in order to improve muscle function, energy efficiency and tissue maintenance of MDC1A and LS patients. PMID:28367954

  2. Joubert syndrome: congenital cerebellar ataxia with the “molar tooth”

    PubMed Central

    Romani, Marta; Micalizzi, Alessia; Valente, Enza Maria

    2013-01-01

    Joubert syndrome (JS) is a congenital cerebellar ataxia with autosomal recessive or X-linked inheritance, which diagnostic hallmark is a unique cerebellar and brainstem malformation recognizable on brain imaging, the “molar tooth sign”. Neurological signs are present from neonatal age and include hypotonia evolving into ataxia, global developmental delay, ocular motor apraxia and breathing dysregulation. These are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton and liver. To date, 21 causative genes have been identified, all encoding for proteins of the primary cilium or its apparatus. This is a subcellular organelle that plays key roles in development and in many cellular functions, making JS part of the expanding family of ciliopathies. There is marked clinical and genetic overlap among distinct ciliopathies, which may co-occur even within families. Such variability is likely explained by an oligogenic model of inheritance, in which mutations, rare variants and polymorphisms at distinct loci interplay to modulate the expressivity of the ciliary phenotype. PMID:23870701

  3. Congenital Adrenal Hyperplasia, Polycystic Ovary Syndrome and criminal behavior: A Swedish population based study.

    PubMed

    Ohlsson Gotby, Agnes; Nordenström, Anna; Falhammar, Henrik; Nordenskjöld, Agneta; Linden Hirschberg, Angelica; Frisén, Louise; Landén, Mikael; Lichtenstein, Paul

    2015-10-30

    Both prenatal and circulating testosterone and other androgens have been suggested to influence the individual's propensity to commit crime, but empirical evidence is limited and inconsistent. Congenital Adrenal Hyperplasia (CAH) and Polycystic Ovary Syndrome (PCOS) are both hyperandrogenic conditions but with an important difference; whereas subjects with CAH are exposed to high concentrations of androgens in utero, women with PCOS are subjected to high androgens in adulthood. Comparing these groups can therefore yield important insights of androgenic effects on behavior. In the current study, information on medical diagnoses and convicted crimes were gathered from Swedish population-based registers. The associations between diagnoses of CAH or PCOS and any crime, violent crime or sex crime were estimated with conditional logistic regression. Results showed that CAH in women and men did not predict criminality, whereas an increased risk for any crime and violent crime was found in PCOS women. Our findings indicate that female hyperandrogenism in adulthood, but not prenatal hyperandrogenism, is associated with risk for criminal behavior. Further research into hyperandrogenic conditions holds opportunities to deepen our understanding of the etiology of crime and psychopathology.

  4. Neurodevelopmental Outcomes in Children with Down Syndrome and Congenital Heart Defects

    PubMed Central

    Visootsak, Jeannie; Mahle, William T.; Kirshbom, Paul; Huddleston, Lillie; Caron-Besch, Marcia; Ransom, Amy; Sherman, Stephanie L

    2011-01-01

    Trisomy 21, the chromosomal condition responsible for Down syndrome (DS, OMIM #190685), is the most common identifiable genetic cause of intellectual disability. Approximately half of all children with DS are born with a significant congenital heart defect (CHD), the most common of which is an atrioventricular septal defect (AVSD). As children with comorbid DS and CHD increasingly survive cardiac surgery, characterization of their early developmental trajectories is critical for designing early interventions to maximize individual potential. Herein, the developmental domains (cognitive, language, and motor) of children with DS and AVSD (DS + AVSD, n=12) were compared to children with DS and a structurally normal heart (DS – CHD, n=17) using the Bayley Scales of Infant and Toddler Development III. The DS + AVSD cohort mean age was relatively the same as controls with DS – CHD, 14.5 ±7.3 months compared with 14.1 ± 8.4 months, respectively. Although the motor domain was the only domain that showed a statistically significant difference between groups (p < .05), both cognitive standard scores (p = 0.63) and language composite standard scores (p = 0.10) were lower in the DS + AVSD cases compared with the DS – CHD controls although it is not statistically significant. Since this is the first study to examine the early developmental outcomes of children with DS + AVSD, the findings may be useful for clinicians in providing anticipatory guidance. PMID:21932314

  5. [Congenital diarrhoea].

    PubMed

    Buda, Piotr; Friedman-Gruszczyńska, Joanna; Książyk, Janusz

    2011-01-01

    Congenital diarrhoea of heterogenic etiology is a rare cause of chronic diarrhoea. Characteristic features are: onset in the first weeks of life, life-threatening severe dehydratation and electrolyte disorders leading to a necessity of long-term parenteral nutrition. The clinical onset may be delayed and the degree of diarrhoea may be modest, making the diagnosis difficult. The main causes of congenital diarrhoea such as intestine electrolytes, carbohydrates, lipid and protein transport disorders and congenital enzymatic deficiencies, enterocyte polarization disorders, hormonal, immunological, metabolic, genetic and congenital anatomic disorders are presented in the paper. Some of them, such as: microvillus inclusion disease, tufting enteropathy, intestinal anedocrynosis, IPEX syndrome (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) have been described recently. One of the basic investigations, when congenital diarrhea is suspected, is general examination of the stool, its electrolyte concentration and serum electrolytes and blood gas analysis. Often, small bowel biopsy with histological examination (with the use of electronic microscopy and PAS staining) is indicated. In some cases molecular examination is possible and indicated. In differential diagnosis other, more frequent causes of chronic diarrhea of infancy, have to be excluded. In most of the cases of congenital diarrhoea there is no casual treatment available - usually long-term parenteral nutrition is necessary.

  6. The combination of vestibular impairment and congenital sensorineural hearing loss predisposes patients to ocular anomalies, including Usher syndrome.

    PubMed

    Kletke, S; Batmanabane, V; Dai, T; Vincent, A; Li, S; Gordon, K A; Papsin, B C; Cushing, S L; Héon, E

    2016-10-15

    The co-occurrence of hearing impairment and visual dysfunction is devastating. Most deaf-blind etiologies are genetically determined, the commonest being Usher syndrome (USH). While studies of the congenitally deaf population reveal a variable degree of visual problems, there are no effective ophthalmic screening guidelines. We hypothesized that children with congenital sensorineural hearing loss (SNHL) and vestibular impairment were at an increased risk of having USH. A retrospective chart review of 33 cochlear implants recipients for severe to profound SNHL and measured vestibular dysfunction was performed to determine the ocular phenotype. All the cases had undergone ocular examination and electroretinogram (ERG). Patients with an abnormal ERG underwent genetic testing for USH. We found an underlying ocular abnormality in 81.81% (27/33) of cases; of which 75% had refractive errors, and 50% of those patients showed visual improvement with refractive correction. A total of 14 cases (42.42%; 14/33) had generalized rod-cone dysfunction on ERG suggestive of Usher syndrome type 1, confirmed by mutational analysis. This work shows that adding vestibular impairment as a criterion for requesting an eye exam and adding the ERG to detect USH increases the chances of detecting ocular anomalies, when compared with previous literature focusing only on congenital SNHL.

  7. Findings from aCGH in patients with congenital diaphragmatic hernia (CDH): a possible locus for Fryns syndrome.

    PubMed

    Kantarci, S; Casavant, D; Prada, C; Russell, M; Byrne, J; Haug, L Wilkins; Jennings, R; Manning, S; Blaise, F; Boyd, T K; Fryns, J P; Holmes, L B; Donahoe, P K; Lee, C; Kimonis, V; Pober, B R

    2006-01-01

    Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect that can occur in isolation or as part of a malformation complex. Considerable progress is being made in the identification of genetic causes of CDH. We applied array-based comparative genomic hybridization (aCGH) of approximately 1Mb resolution to 29 CDH patients with prior normal karyotypes who had been recruited into our multi-site study. One patient, clinically diagnosed with Fryns syndrome, demonstrated a de novo 5Mb deletion at chromosome region 1q41-q42.12 that was confirmed by FISH. Given prior reports of CDH in association with cytogenetic abnormalities in this region, we propose that this represents a locus for Fryns syndrome, a Fryns syndrome phenocopy, or CDH.

  8. Occlusive vascular Ehlers-Danlos syndrome accompanying a congenital cystic adenomatoid malformation of the lung: report of a case.

    PubMed

    Sa, Young Jo; Kim, Young Du; Moon, Seok-Whan; Kim, Chi-Kyung; Ki, Chang Seok

    2013-12-01

    An 8-year-old male presented with a cystic lung lesion in the left lower lobe, which was initially detected during surgery for a spontaneous rupture of the sigmoid colon at the age of 6 years. Tissue fragility and a tendency to bleed easily were noted during the surgery, which strongly suggested vascular Ehlers-Danlos syndrome. Although there was no abnormality in the hemostasis screening test, or any suspicious hereditary problem in his pedigree, genetic gene testing for vascular Ehlers-Danlos syndrome was recommended, and showed a de novo mutation in the COL3A1 gene. This report presents the case of patient with occlusive vascular Ehlers-Danlos syndrome accompanying a congenital cystic adenomatoid malformation of lung, in addition to a duplicated infrarenal vena cava.

  9. Surveillance of congenital rubella syndrome in Japan, 1978-2002: effect of revision of the immunization law.

    PubMed

    Katow, Shigetaka

    2004-09-28

    Infection of rubella virus at the early stages of pregnancy in women who are not immune to rubella often induces congenital anomalies in infants, namely congenital rubella syndrome (CRS). This paper is the first comprehensive report of CRS cases in Japan, compiled from a questionnaire to major hospitals, reports to journals and academic meetings, and cases for virus/virus genome verification submitted to the National Institute of Infectious Diseases. CRS incidence in Japan was determined to be 0.2-8.1 cases/100,000 live births per year in epidemic years and 0.1-0.7 in non-epidemic years, respectively. In the last 4 years, the number of CRS cases remarkably decreased to one-three cases per year. This decrease is thought to be because the immunization law was revised in 1994 for changing the focus of rubella immunization from junior high school girls to infants of both sexes.

  10. Unknown syndrome: abnormal facies, congenital heart defects, hypothyroidism, and severe retardation.

    PubMed Central

    Young, I D; Simpson, K

    1987-01-01

    We present a female infant with (1) abnormal facies: microcephaly, blepharophimosis, small, low set, posteriorly rotated ears, bulbous nose, carp shaped mouth, micrognathia; (2) congenital heart abnormalities: large atrial and ventricular septal defects; (3) congenital hypothyroidism; (4) severe global retardation. Images PMID:3430551

  11. Hemiconvulsion-Hemiplegia-Epilepsy syndrome associated with inflammatory-degenerative hystopathological findings in child with congenital adrenal hyperplasia.

    PubMed

    Serino, Domenico; Camassei, Francesca Diomedi; Delalande, Olivier; Marras, Carlo E; Specchio, Nicola; Vigevano, Federico; Fusco, Lucia

    2014-05-01

    Hemiconvulsion-Hemiplegia (HH) syndrome represents an uncommon consequence of prolonged unilateral clonic or hemiconvulsive status epilepticus in childhood, usually occurring during a febrile illness, followed by ipsilateral hemiplegia. The subsequent appearance of focal seizures configures the so called Hemiconvulsion-Hemiplegia-Epilepsy (HHE) syndrome. The pathogenesis of HH/HHE syndrome is still unclear. We describe the case of a 4 year-old girl with congenital adrenal hyperplasia (CAH) whom developed HH/HHE syndrome with drug resistant seizures at the age of 21 months and underwent left cerebral hemispherotomy at the age of 3 years and 6 months. Histopathological findings showed the presence of an underlying inflammatory-degenerative process. Disregulation of the inflammatory cascade has been proposed as one of the possible pathogenetic mechanisms underlying HH/HHE syndrome. To our knowledge however, this is the first report of an association with a histologically documented inflammatory process. The clinical and histopathological findings of our reported case lend support to the possible role of inflammation in the pathogenesis of HH/HHE syndrome.

  12. The cerebral cost of breathing: an FMRI case-study in congenital central hypoventilation syndrome.

    PubMed

    Sharman, Mike; Gallea, Cécile; Lehongre, Katia; Galanaud, Damien; Nicolas, Nathalie; Similowski, Thomas; Cohen, Laurent; Straus, Christian; Naccache, Lionel

    2014-01-01

    Certain motor activities--like walking or breathing--present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks--including various frontal lobe areas--subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the "resting state" pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active

  13. Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome

    PubMed Central

    Harper, Ronald M.; Kumar, Rajesh; Macey, Paul M.; Harper, Rebecca K.; Ogren, Jennifer A.

    2015-01-01

    Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure

  14. Epidemiology of rubella and congenital rubella syndrome in Japan before 1989.

    PubMed

    Ueda, Kohji

    2016-04-07

    Epidemiological studies of rubella and congenital rubella syndrome (CRS) in Japan have been conducted since the first nationwide rubella epidemic of 1965-1969 and subsequent epidemics of 1975-1977, 1982, 1987-1988, and 1992-1993. Rubella was non-endemic in Japan before the 1975-1977 epidemic, and endemic thereafter. Japan started a selective rubella vaccination program for junior high school girls in 1977, and universal rubella vaccination of children of both sexes in 1989. No nationwide rubella epidemics have occurred since 1994. Only three children with CRS were reported in Japan before 1964; however, many children with CRS were identified in 1965 when a rubella epidemic struck Okinawa, which has many the United States military bases. After the 1965-1969 and 1975-1977 rubella epidemics on the Japanese mainland, small numbers of children with CRS were identified (hospital survey). These findings led to the hypothesis that, compared to U.S. rubella virus strains, Japanese strains of rubella virus are less teratogenic. This hypothesis strongly affected the development of rubella vaccines in Japan. However, retrospective seroepidemiological studies attributed the CRS in many children in Okinawa to the high rate of rubella infection in pregnant women. According to the survey conducted at special schools for the deaf, 83, 232, 77, and 167 children were born with CRS on the Japanese mainland respectively after the 1965-1969, 1975-1977, 1982, and 1987-1988 nationwide rubella epidemics, suggesting that the incidence of CRS in Japan is in fact comparable to that in the U.S. and Europe. Rubella epidemics in children have been effectively prevented since 1994. However, a rubella outbreak among adult males and CRS occurred between 2012 and 2014.

  15. Voxel-based morphometry and intellectual assessment in patients with congenital bilateral perisylvian syndrome.

    PubMed

    Yasuda, Clarissa L; Guimarães, Catarina A; Guerreiro, Marilisa M; Boscariol, Mirela; Oliveira, Ecila P M; Teixeira, Karine C; Costa, André L F; Beltramini, Guilherme C; Cendes, Fernando

    2014-07-01

    Congenital bilateral perisylvian syndrome (CBPS) presents with heterogeneous clinical manifestations such as pseudobulbar palsy, language disorder, variable cognitive deficits, epilepsy, and perisylvian abnormalities (most frequently polymicrogyria) on imaging studies. We investigated the relationship between seizures and extent of gray matter (GM) and white matter (WM) abnormalities using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI) as well the association between seizures, structural abnormalities and cognitive ability. In this cross-sectional study, we evaluated 51 healthy volunteers and 18 patients with CBPS with epilepsy (seizure group, n = 7) and without (non-seizure group, n = 11). We used VBM (SPM8/DARTEL) to investigate areas with excess and atrophy of both gray and white matter, comparing groups of patients with controls. Intellectual ability of patients was assessed by the WISC-III or WAIS-III. Both groups with CBPS and the control group were homogeneous with respect to gender (p = 0.07) and age (p = 0.065). Besides perisylvian polymicrogyria, the seizure group exhibited areas with GM and WM reduction including temporal, frontal, parietal and occipital lobes. In contrast, we identified fewer areas with GM and WM reduction in the non-seizure group. The seizure group presented worse intellectual performance (performance IQ and global IQ) than the non-seizure group. The seizure group presented with a more widespread pattern of cortical and sub-cortical abnormalities, as well as worse cognition. Our results suggest that patients with CBPS and epilepsy appear to have widespread neuronal damage that goes beyond the areas with MRI-visible perisylvian polymicrogyria.

  16. Cleft Palate, Retrognathia and Congenital Heart Disease in Velo-Cardio-Facial Syndrome: A Phenotype Correlation Study

    PubMed Central

    Friedman, Marcia A.; Miletta, Nathanial; Roe, Cheryl; Wang, Dongliang; Morrow, Bernice E.; Kates, Wendy R.; Higgins, Anne Marie; Shprintzen, Robert J.

    2011-01-01

    Objective Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. Methods This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by chi square or Fisher exact test. Results For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p=0.0325) and occult submucous cleft palate and retrognathia (nominal p=0.000013). Conclusions Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some

  17. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism.

    PubMed

    Senée, Valérie; Chelala, Claude; Duchatelet, Sabine; Feng, Daorong; Blanc, Hervé; Cossec, Jack-Christophe; Charon, Céline; Nicolino, Marc; Boileau, Pascal; Cavener, Douglas R; Bougnères, Pierre; Taha, Doris; Julier, Cécile

    2006-06-01

    We recently described a new neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys. Here, we show that this syndrome results from mutations in GLIS3, encoding GLI similar 3, a recently identified transcription factor. In the original family, we identified a frameshift mutation predicted to result in a truncated protein. In two other families with an incomplete syndrome, we found that affected individuals harbor deletions affecting the 11 or 12 5'-most exons of the gene. The absence of a major transcript in the pancreas and thyroid (deletions from both families) and an eye-specific transcript (deletion from one family), together with residual expression of some GLIS3 transcripts, seems to explain the incomplete clinical manifestations in these individuals. GLIS3 is expressed in the pancreas from early developmental stages, with greater expression in beta cells than in other pancreatic tissues. These results demonstrate a major role for GLIS3 in the development of pancreatic beta cells and the thyroid, eye, liver and kidney.

  18. Management of ventricular fibrillation or unstable ventricular tachycardia in patients with congenital long-QT syndrome: a suggested modification to ACLS guidelines.

    PubMed

    Homme, Jason H; White, Roger D; Ackerman, Michael J

    2003-10-01

    Prolongation of the QT interval is a known risk factor for syncope, seizures and sudden cardiac death. Most patients with QT prolongation have an acquired cause, but congenital forms of QT prolongation are being increasingly recognized. However, existing advanced cardiac life support (ACLS) treatment algorithms for prolonged QT mediated ventricular fibrillation pertains to acquired long-QT syndrome (LQTS). Here, a young patient with out-of-hospital cardiac arrest secondary to congenital LQTS illustrates critical exceptions to the current ACLS treatment algorithms for ventricular fibrillation and unstable ventricular tachycardia when QT prolongation is congenital in origin. A clarified ACLS algorithm is proposed.

  19. Coffin-Siris syndrome with the rarest constellation of congenital cardiac defects: A case report with review of literature

    PubMed Central

    Nemani, Lalita; Barik, Ramachandra; Patnaik, Amar Narayana; Mishra, Ramesh C; Rao, Amaresh M; Kapur, Pragati

    2014-01-01

    We report a case of type-A Coffin-Siris syndrome (CSS) with a unique constellation of congenital heart defects. A 17-year-old Indian boy was referred to our hospital for central cyanosis with features of right heart failure. The cardiac abnormalities included biventricular outflow tract obstruction, small atrial septal defect (ASD), subaortic ventricular septal defect, drainage of left superior venacava to left atrial appendage, and aortic arch anomaly. Patient underwent successful right ventricular infundibular resection, subaortic membrane resection, closure of atrial and ventricular septal defect, rerouting left superior vena cava to left pulmonary artery and aortic valve replacement. PMID:25298701

  20. Congenital high airway obstruction syndrome without tracheoesophageal fistula and with in utero decrease in relative lung size.

    PubMed

    Furukawa, Rieko; Aihara, Toshinori; Tazuke, Yuko; Maeda, Kosaku; Kuwata, Tomoyuki

    2012-12-01

    Congenital high airway obstruction syndrome (CHAOS) is diagnosed by characteristic features on US and MRI including fetal upper airway occlusion, lung hyperinflation with an inverted diaphragm, and sometimes massive ascites and hydrops. We describe a case of CHAOS in which improvement in the fetal condition was observed on three sequential fetal MRIs. Such an improvement was thought to represent decrease in intrathoracic pressure caused by a spontaneous perforation such as a tracheoesophageal fistula. However, a fistula was not observed in the present case. Therefore, we suggest that imaging improvements in patients with CHAOS do not always correspond to the presence of a fistula and other factors might contribute to decreasing fetal intrathoracic pressure.

  1. Coffin-Siris syndrome with the rarest constellation of congenital cardiac defects: A case report with review of literature.

    PubMed

    Nemani, Lalita; Barik, Ramachandra; Patnaik, Amar Narayana; Mishra, Ramesh C; Rao, Amaresh M; Kapur, Pragati

    2014-09-01

    We report a case of type-A Coffin-Siris syndrome (CSS) with a unique constellation of congenital heart defects. A 17-year-old Indian boy was referred to our hospital for central cyanosis with features of right heart failure. The cardiac abnormalities included biventricular outflow tract obstruction, small atrial septal defect (ASD), subaortic ventricular septal defect, drainage of left superior venacava to left atrial appendage, and aortic arch anomaly. Patient underwent successful right ventricular infundibular resection, subaortic membrane resection, closure of atrial and ventricular septal defect, rerouting left superior vena cava to left pulmonary artery and aortic valve replacement.

  2. Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR?

    PubMed

    Grasso, Valeria; Colombo, Carlo; Favalli, Valeria; Galderisi, Alfonso; Rabbone, Ivana; Gombos, Sara; Bonora, Enzo; Massa, Ornella; Meschi, Franco; Cerutti, Franco; Iafusco, Dario; Bonfanti, Riccardo; Monciotti, Carla; Barbetti, Fabrizio

    2013-12-01

    Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). At presentation, DS and RMS are difficult to differentiate since they share many clinical features; however, while patients with DS usually die within 1 year of birth, individuals classified as RMS can reach adult age. INSR mutations can be also found in pubertal females with hyperinsulinism, hyperandrogenism, and acanthosis nigricans (type A SIR). We studied the INSR gene in five subjects with congenital SIR and in a patient with type A SIR. Nine biallelic INSR gene mutations (eight novels, including an in-frame deletion of INSR signal peptide) were identified in patients with congenital SIR; a heterozygous, spontaneous INSR mutation was detected in the patient with type A SIR. Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4). The fifth patient with congenital SIR died when 14 months old. Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively. Patient 3, now 3 years/3 months old, still shows hyperreninemic hyperaldosteronism requiring potassium supplementation. We conclude that renal abnormalities resembling antenatal Bartter's syndrome type II, recently reported also by others, is a common observation in patients with congenital SIR.

  3. Surgical management of a large peritoneal pseudocyst causing acute kidney injury secondary to abdominal compartment syndrome in a rare case of congenital absence of omentum during pregnancy.

    PubMed

    Jones, Benjamin P; Hunjan, Tia; Terry, Jayne

    2016-09-01

    Complete congenital absence of the omentum is very rare with only one previously reported case. We present a unique case of the management of a pregnant woman with a large pelvic pseudocyst caused by complications related to congenital absence of omentum, resulting in acute kidney injury, likely secondary to acute compartment syndrome. This case highlights the importance of considering acute compartment syndrome in critically unwell pregnant women and reiterates the need to measure intra-abdominal pressure when clinically indicated. Given that pregnancy is in itself a state of intra-abdominal hypertension, obstetricians should maintain a high index of suspicion in the context of additional risk factors.

  4. Nutritional intakes in children with Prader–Willi syndrome and non-congenital obesity

    PubMed Central

    Rubin, Daniela A.; Nowak, Jill; McLaren, Erin; Patiño, Monzeratt; Castner, Diobel M.; Dumont-Driscoll, Marilyn C.

    2015-01-01

    Background Individuals with Prader–Willi syndrome (PWS) have extremely regulated diets to prevent the development of morbid obesity. Objective This study evaluated potential deficiencies in macro and micronutrients in a cohort of youth with PWS and compared them to a group of children with non-congenital obesity and to US national recommendations. Design Participants were 32 youth with PWS (age=10.8±2.6 years, body fat=46.7±10.1%) and 48 children without PWS but classified as obese (age=9.7±1.2 years, body fat=43.4±5.7%). Participants’ parents completed a training session on food recording before completing a 3-day food record during a typical week including a weekend day and two weekdays, as well as a screening form indicating nutritional supplements use. Results Youth with PWS reported less calories (1,312±75 vs. 1,531±61 kcal, p=0.03), carbohydrate (175±10 vs. 203±8 g), and sugars (67±5 vs. 81±4 g; p=0.04 for both) than obese. Youth with PWS consumed more vegetables (1.1±0.1 vs. 0.6±0.1 cups) and more of them met the daily recommendation (p<0.01 for both). Likewise, youth with PWS consumed more calcium than obese (899±53 vs. 752±43 mg) and more of them met the recommended daily dose (p=0.04 for both). The majority of participants in this study did not meet the vitamin D recommendation. Conclusion Despite consuming less calories, youth with PWS had a similar proportion of macronutrients in their diet as children with obesity. Micronutrient deficiencies in calcium and vitamin D in youth with PWS were noted despite a third of youth with PWS consuming multivitamin supplements. Special attention must be paid to the diets of youth with PWS and with obesity to ensure they are meeting micronutrient needs during this period of growth and development. PMID:26652260

  5. Hospitalizations and mortality in the United States for adults with Down syndrome and congenital heart disease.

    PubMed

    Baraona, Fernando; Gurvitz, Michelle; Landzberg, Michael J; Opotowsky, Alexander R

    2013-04-01

    Congenital heart disease (CHD) is common in patients with Down syndrome (DS), and these patients are living longer lives. The aim of this study was to describe the epidemiology of hospitalizations in adults with DS and CHD in the United States. Hospitalizations from 1998 to 2009 for adults aged 18 to 64 years with and without DS with CHD diagnoses associated with DS (atrioventricular canal defect, ventricular septal defect, tetralogy of Fallot, and patent ductus arteriosus) were analyzed using the Nationwide Inpatient Sample. Outcomes of interest were (1) in-hospital mortality, (2) common co-morbidities, (3) cardiac procedures, (4) hospital charges, and (5) length of stay. Multivariate modeling adjusted for age, gender, CHD diagnosis, and co-morbidities. There were 78,793 ± 2,653 CHD admissions, 9,088 ± 351 (11.5%) of which were associated with diagnoses of DS. The proportion of admissions associated with DS (DS/CHD) decreased from 15.2 ± 1.3% to 8.5 ± 0.9%. DS was associated with higher in-hospital mortality (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.4 to 2.4), especially in women (OR 2.4, 95% CI 1.7 to 3.4). DS/CHD admissions were more commonly associated with hypothyroidism (OR 7.7, 95% CI 6.6 to 9.0), dementia (OR 82.0, 95% CI 32 to 213), heart failure (OR 2.2, 95% CI 1.9 to 2.5), pulmonary hypertension (OR 2.5, 95% CI 2.2 to 2.9), and cyanosis or secondary polycythemia (OR 4.6, 95% CI 3.8 to 5.6). Conversely, DS/CHD hospitalizations were less likely to include cardiac procedures or surgery (OR 0.3, 95% CI 0.2 to 0.4) and were associated with lower charges ($23,789 ± $1,177 vs $39,464 ± $1,371, p <0.0001) compared to non-DS/CHD admissions. In conclusion, DS/CHD hospitalizations represent a decreasing proportion of admissions for adults with CHD typical of DS; patients with DS/CHD are more likely to die during hospitalization but less likely to undergo a cardiac procedure.

  6. A boy with homozygous microdeletion of NEUROG1 presents with a congenital cranial dysinnervation disorder [Moebius syndrome variant

    PubMed Central

    2013-01-01

    Background We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay. Further findings included scaphocephaly, plagiocephaly, long palpebral fissures, high narrow palate, low-set posteriorly rotated ears, torticollis, hypoplastic genitalia and faulty foot posture. Parents were consanguineous. Methods and results Computed tomography and magnetic resonance imaging showed bilateral single widened cochlear turn, narrowing of the internal auditory canal, and bilateral truncation of the vestibulo-cochlear nerve. Microarray analysis and next generation sequencing showed a homozygous deletion of chromosome 5q31.1 spanning 115.3 kb and including three genes: NEUROG1 (encoding neurogenin 1), DCNP1 (dendritic cell nuclear protein 1, C5ORF20) and TIFAB (TIFA-related protein). The inability to chew and swallow, deafness and balance disorder represented congenital palsies of cranial nerves V (trigeminal nerve) and VIII (vestibulo-cochlear nerve) and thus a congenital cranial dysinnervation disorder. Conclusions Based on reported phenotypes of neurog1 null mutant mice and other vertebrates, we strongly propose NEUROG1 as the causative gene in this boy. The human NEUROG1 resides within the DFNB60 locus for non-syndromic autosomal recessive deafness on chromosome 5q22-q31, but linkage data have excluded it from being causative in the DFNB60 patients. Given its large size (35 Mb, >100 genes), the 5q22-q31 area could harbor more than one deafness gene. We propose NEUROG1 as a new gene for syndromic autosomal recessive hearing loss and congenital cranial dysinnervation disorder including cranial nerves V and VIII. PMID:23419067

  7. Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome.

    PubMed

    Armstrong, Amy E; Weese-Mayer, Debra E; Mian, Amir; Maris, John M; Batra, Vandana; Gosiengfiao, Yasmin; Reichek, Jennifer; Madonna, Mary Beth; Bush, Jonathan W; Shore, Richard M; Walterhouse, David O

    2015-11-01

    Neuroblastoma in patients with congenital central hypoventilation syndrome (CCHS) as part of a neurocristopathy syndrome is a rare finding and has only been associated with paired-like homeobox 2b (PHOX2B) non-polyalanine-repeat-expansion mutations. To the best of our knowledge, we report the first case of a child with CCHS and Hirschsprung disease who had a PHOX2B polyalanine-repeat-expansion mutation (PARM) (genotype 20/33) and developed high-risk neuroblastoma. We further describe his treatment including chemotherapy and therapeutic I(131) -metaiodobenzylguanidine. This case highlights the need to consider neuroblastoma in patients with CCHS and the longest PHOX2B PARMs and to individualize treatment based on co-morbidities.

  8. Life and death of a child with down syndrome and a congenital heart condition: experiences of six couples.

    PubMed

    Reilly, Deirdre; Huws, Jaci; Hastings, Richard; Vaughan, Frances

    2010-12-01

    Individuals with Down syndrome are at increased risk of congenital heart conditions (CHCs), and mortality is higher in people with Down syndrome and a CHC than those without (J. C. Vis et al., 2009). As a consequence, parents of children with Down syndrome and a CHC are more likely to outlive their child. In this research, semistructured interviews were used to explore the experiences of 6 couples whose child with Down syndrome and a CHC had died. The interviews were analyzed qualitatively using interpretative phenomenological analysis (IPA), and 4 themes emerged: dilemmas associated with the dual diagnosis; treatment decisions during the life and the death of their child ("We had to make a decision"); ways couples coped when bereaved ("We weren't really going through it together"); and ripples from the child's life. There was a high degree of similarity of experience within couples. Differences between couples existed in their experiences of coping and supporting each other. Practical implications include the importance of considering the specific needs of couples, individuals, and fathers within partnerships.

  9. Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

    PubMed

    Rodrigues, A L; Carvalho, A; Cabral, R; Carneiro, V; Gilardi, P; Duarte, C P; Puente-Prieto, J; Santos, P; Mota-Vieira, L

    2014-07-25

    Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

  10. Accelerate Genomic Aging in Congenital Neutropenia

    DTIC Science & Technology

    2015-08-01

    myeloid leukemia (AML) is perhaps the major clinical concern in patients with severe congenital neutropenia (SCN) and Shwachman- Diamond syndrome (SDS... Diamond syndrome (SDS), cyclic neutropenia, or age-matched healthy controls. Aim 2. To determine whether increased G-CSF signaling accelerates the...agents, such as radiation. 2. KEYWORDS Congenital neutropenia Severe congenital neutropenia Shwachman Diamond syndrome Cyclic neutropenia

  11. [Mosaic isochromosome Xq and microduplication 17p13.3p13.2 in a patient with Turner syndrome and congenital cataract].

    PubMed

    Rojas Martínez, Jorge A; Acosta Guio, Johanna C

    2015-01-01

    The combination of Turner syndrome with other genetic disorders such as congenital cataract has been reported, but its association with a congenital form with autosomal dominant inheritance and incomplete penetrance has not been previously reported in the literature. There are no reports on its presentations with rearrangements on chromosome 17. We report the exceptional case of a 20 months old girl with a constellation of major and minor anomalies, diagnosed with mosaic Turner syndrome by isochromosome Xq associated with a microduplication 17p13.3p13.2, who also had bilateral congenital nuclear cataract autosomal dominant with incomplete penetrance. We reviewed in the literature the origin and cause of these genetic alterations and we provided an approach to the hypothesis of the pathogenesis of the association of two of these genetic disorders in the same patient.

  12. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)

    PubMed Central

    Ferguson, P; Chen, S; Tayeh, M; Ochoa, L; Leal, S; Pelet, A; Munnich, A; Lyonnet, S; Majeed, H; El-Shanti, H

    2005-01-01

    Background: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation. Methods: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out. Results: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown. Conclusions: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis. PMID:15994876

  13. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    PubMed

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

  14. Lethal congenital muscular dystrophy in two sibs with arthrogryposis multiplex: new entity or variant of cobblestone lissencephaly syndrome?

    PubMed

    Seidahmed, M Z; Sunada, Y; Ozo, C O; Hamid, F; Campbell, K P; Salih, M A

    1996-12-01

    We report on two sisters of first degree cousin parents who were born with severe hypotonia, arthrogryposis multiplex congenita (AMC) and dysmorphic features consistent with the fetal akinesia/hypokinesia sequence. They needed assisted ventilation and each died at the age of 5 months. Both had type II lissencephaly (cobblestone lissencephaly) which was visualized by magnetic resonance imaging (MRI) in the proband. Ophthalmic evaluation revealed no ocular malformations in either of them. Brain auditory evoked potentials (BAEP) revealed bilateral severe sensorineural hearing loss in the proband, whereas an MRI-guided open muscle biopsy of the sartorius muscle (the only remaining thigh muscle) showed features of muscular dystrophy. Immunohistochemistry revealed normal dystrophin, dystrophin-associated glycoproteins (DAG) and merosin. Certain clinical and pathological features distinguish the disease seen in these sisters from reported isolated cases where lethal AMC was associated with brain dysplasia and from the main syndromes of congenital muscular dystrophy/cobblestone lissencephaly. Differences from the Walker-Warburg syndrome, which simulates it in severity, included the absence of severe hydrocephalus, normal creatine kinase (for age) and minimal (mainly periventricular) white matter abnormalities. The findings suggest either an independent entity, in the studied family, or an allelic variation of the cobblestone lissencephaly (type II lissencephaly) syndrome.

  15. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome

    PubMed Central

    Mlynarski, Elisabeth E.; Xie, Michael; Taylor, Deanne; Sheridan, Molly B.; Guo, Tingwei; Racedo, Silvia E.; McDonald-McGinn, Donna M.; Chow, Eva W. C.; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J.; Roberts, Amy E.; Piotrowicz, Małgorzata; Bearden, Carrie E.; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R.; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S.; Morrow, Bernice E.

    2016-01-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60–75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients. PMID:26742502

  16. A novel FGD1 mutation in a family with Aarskog–Scott syndrome and predominant features of congenital joint contractures

    PubMed Central

    Griffin, Laurie Beth; Farley, Frances A.; Antonellis, Anthony; Keegan, Catherine E.

    2016-01-01

    Mutations in FGD1 cause Aarskog–Scott syndrome (AAS), an X-linked condition characterized by abnormal facial, skeletal, and genital development due to abnormal embryonic morphogenesis and skeletal formation. Here we report a novel FGD1 mutation in a family with atypical features of AAS, specifically bilateral upper and lower limb congenital joint contractures and cardiac abnormalities. The male proband and his affected maternal uncle are hemizygous for the novel FGD1 mutation p.Arg921X. This variant is the most carboxy-terminal FGD1 mutation identified in a family with AAS and is predicted to truncate the FGD1 protein at the second to last amino acid of the carboxy-terminal pleckstrin homology (PH) domain. Our study emphasizes the importance of the 3′ peptide sequence in the structure and/or function of the FGD1 protein and further demonstrates the need to screen patients with X-linked congenital joint contractures for FGD1 mutations. PMID:27551683

  17. Fluctuating Kluver-Bucy syndrome in a child with epilepsy due to bilateral anterior temporal congenital malformations.

    PubMed

    Pestana, Elia M; Gupta, Ajay

    2007-03-01

    An 11-year-old boy with epilepsy due to congenital bilateral anterior temporal lobe malformations presented with fluctuating Kluver-Bucy syndrome (KBS). Since the age of 2, he had experienced clusters of three or four daily complex partial seizures over 2-3 days in a month, followed by a seizure-free interval of 3-4 weeks. During the seizure-free period, the patient exhibited hyperorality, sniffing, irritability alternating with placidity, anxiety, unsolicited sexual gestures, and unusual calmness after eating. KBS features escalated up to the onset of the seizure cluster, and remitted after the seizures. Brain MRI revealed bilateral anterior temporal cortical dysplasia with enlarged and dysmorphic amygdalar-hippocampal complex. Brain [(18)F]fluorodeoxyglucose positron emission tomography PET showed bilateral anterior and mesial temporal hypometabolism. Video/EEG monitoring revealed independent right and left temporal lobe seizures. This is the first reported case of KBS due to congenital bitemporal malformations. Also, KBS behavior phenotype in this patient fluctuated, with escalation during the seizure-free period and remission induced by the monthly seizure cluster. This fluctuating pattern could represent forced normalization.

  18. Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype

    PubMed Central

    Skauli, Nadia; Wallace, Sean; Chiang, Samuel C. C.; Barøy, Tuva; Holmgren, Asbjørn; Stray-Pedersen, Asbjørg; Bryceson, Yenan T.; Strømme, Petter; Frengen, Eirik; Misceo, Doriana

    2016-01-01

    Biallelic PIGT variants were previously reported in seven patients from three families with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), characterized by epileptic encephalopathy, hypotonia, global developmental delay/intellectual disability, cerebral and cerebellar atrophy, craniofacial dysmorphisms, and skeletal, ophthalmological, cardiac, and genitourinary abnormalities. We report a novel homozygous PIGT missense variant c.1079G>T (p.Gly360Val) in two brothers with several of the typical features of MCAHS3, but in addition, pyramidal tract neurological signs. Notably, they are the first patients with MCAHS3 without skeletal, cardiac, or genitourinary anomalies. PIGT encodes a crucial subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, which catalyzes the attachment of proteins to GPI-anchors, attaching the proteins to the cell membrane. In vitro studies in cells from the two brothers showed reduced levels of GPI-anchors and GPI-anchored proteins on the cell surface, supporting the pathogenicity of the novel PIGT variant. PMID:27916860

  19. Congenital immunodeficiency in an individual with Wiedemann-Steiner syndrome due to a novel missense mutation in KMT2A.

    PubMed

    Stellacci, Emilia; Onesimo, Roberta; Bruselles, Alessandro; Pizzi, Simone; Battaglia, Domenica; Leoni, Chiara; Zampino, Giuseppe; Tartaglia, Marco

    2016-09-01

    Wiedemann-Steiner Syndrome (WSS) is an autosomal dominant disorder characterized by hypertrichosis, short stature, intellectual disability, developmental delay, and facial dysmorphism. Since the original reports by Wiedemann and co-workers, and Steiner and Marques, only a few cases have been described. Recently, the clinical variability of the disorder has more precisely been characterized by Jones and co-workers, who also identified heterozygous KMT2A mutations as the molecular defect underlying this condition. Here, we report on a boy with a complex phenotype overlapping WSS but exhibiting epilepsy, feeding difficulties, microcephaly, and congenital immunodeficiency with low levels of immunoglobulins as additional features. Whole exome sequencing allowed identifying a previously unreported de novo KMT2A missense mutation affecting the DNA binding domain of the methyltransferase. This finding expands the clinical phenotype associated with KMT2A mutations to include immunodeficiency and epilepsy as clinically relevant features for this disorder. © 2016 Wiley Periodicals, Inc.

  20. Anterior corpus callosotomy combined with anterior temporal resection with amygdalohippocampectomy: outcome in a patient with congenital bilateral perisylvian syndrome.

    PubMed

    Junming, Zhu; Yuanyuan, Zhao; Fang, Feng; Weiming, Fu; Ryan, Hays; Jianmin, Zhang; Li, Feng; Xiao, Jin; Shuda, Chen

    2014-01-01

    Congenital bilateral perisylvian syndrome (CBPS) is characterized by epilepsy, cognitive deficits, pseudobulbar palsy and diplegia of the facial, pharyngeal and masticatory muscles. Epilepsy has been described in nearly 90% of affected patients. The epilepsy is usually severe and pharmacoresistant in about 55 percent of CBPS patients. Until now, only 12 cases of surgical treatment on CBPS have been reported; the surgical treatment is usually corpus callosotomy. In this paper, we describe a previously unreported combination of anterior corpus callosotomy plus anterior temporal lobectomy with amygdalohippocampectomy for a patient with CBPS, resulting in a satisfactory clinical outcome. Based on this case, we suggest that palliative focal resective surgery combined with anterior corpus callosotomy should be considered when a predominance of the epileptiform discharges suggests focal onset in patients with CBPS. Meanwhile, the clinical decision to adopt this combination surgery must be based on a thorough pre-surgical evaluation, and should take into account the clinical, radiological, and EEG features.

  1. Hybrid Stage I Procedure as Initial Palliation for Neonate With Hypoplastic Left Heart Syndrome and Right Congenital Diaphragmatic Hernia.

    PubMed

    Cvetkovic, Draginja; Giamelli, Joseph; Lyew, Michael; Erb, Markus; Sett, Suvro; DiStefano, Youmna

    2017-01-01

    During the past decade, a hybrid procedure has emerged and dramatically evolved as an alternative stage I palliation to the conventional Norwood procedure in neonates with hypoplastic left heart syndrome (HLHS). The hybrid approach avoids the need for cardiopulmonary bypass (CPB) utilizing stenting of the arterial duct and bilateral pulmonary artery banding. Cerebral and coronary perfusion pressure is maintained, and the pulmonary vasculature is protected from higher systemic pressure. Elimination of risks associated with CPB gains vital time to stabilize the patient and correct coexisting noncardiac anomalies and allows growth in preparation for the later stages of the Fontan pathway. The association of HLHS with right congenital diaphragmatic hernia (CDH) is rare. We report performing a successful hybrid stage I palliation on a neonate with HLHS and severe right CDH.

  2. Congenital diaphragmatic hernia in Smith-Magenis syndrome: a possible locus at chromosome 17p11.2.

    PubMed

    Sanford, E F; Bermudez-Wagner, K; Jeng, L J B; Rauen, K A; Slavotinek, Anne M

    2011-11-01

    We report on a 7-month-old girl with Smith-Magenis syndrome (SMS) due to a 4.76-Mb deletion of 17p12-17p11.2 detected by array comparative genomic hybridization. She was also affected with a left-sided congenital diaphragmatic hernia (CDH) and cardiac anomalies including an atypical atrioventricular canal defect and a cleft mitral valve. To our knowledge, this is the first reported case of a patient with both SMS and CDH. There are numerous chromosomal regions in which duplications, deletions, inversions, or translocations have been associated with CDH, but none have previously been reported at or close to 17p11.2. We discuss candidate genes for the diaphragmatic defect in this patient. Our case demonstrates that it is important to consider the possibility of SMS in non-isolated cases of diaphragmatic hernia.

  3. Unilateral right pulmonary artery agenesis and congenital cystic adenomatoid malformation of the right lung with Ortner's syndrome.

    PubMed

    David, Jane Jackie; Mohanlal, Smilu; Sankhe, Punam; Ghildiyal, Radha

    2016-01-01

    We report a 2.5-year-old girl who presented with hoarseness of voice since 3 months of age and failure to thrive. Chest X-ray showed cardiomegaly with a deviation of the trachea and mediastinum to the right side. Two-dimensional echocardiography showed decreased flow across the right pulmonary artery, a small atrial septal defect (ASD) with a right-to-left shunt, and a dilated right atrium and right ventricle with severe tricuspid regurgitation suggestive of severe pulmonary hypertension. A silent large patent ductus arteriosus was also seen. Multiple detector computerized tomography aortogram confirmed the findings of absent right pulmonary artery and hypoplastic right lung with small cystic lesions suggestive of congenital cystic adenomatoid malformation in the right lower lobe. Hoarseness of voice was due to the left vocal cord palsy probably secondary to severe pulmonary hypertension (Ortner's syndrome).

  4. Mutations in contactin-1, a neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy.

    PubMed

    Compton, Alison G; Albrecht, Douglas E; Seto, Jane T; Cooper, Sandra T; Ilkovski, Biljana; Jones, Kristi J; Challis, Daniel; Mowat, David; Ranscht, Barbara; Bahlo, Melanie; Froehner, Stanley C; North, Kathryn N

    2008-12-01

    We have previously reported a group of patients with congenital onset weakness associated with a deficiency of members of the syntrophin-alpha-dystrobrevin subcomplex and have demonstrated that loss of syntrophin and dystrobrevin from the sarcolemma of skeletal muscle can also be associated with denervation. Here, we have further studied four individuals from a consanguineous Egyptian family with a lethal congenital myopathy inherited in an autosomal-recessive fashion and characterized by a secondary loss of beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma, central nervous system involvement, and fetal akinesia. We performed homozygosity mapping and candidate gene analysis and identified a mutation that segregates with disease within CNTN1, the gene encoding for the neural immunoglobulin family adhesion molecule, contactin-1. Contactin-1 transcripts were markedly decreased on gene-expression arrays of muscle from affected family members compared to controls. We demonstrate that contactin-1 is expressed at the neuromuscular junction (NMJ) in mice and man in addition to the previously documented expression in the central and peripheral nervous system. In patients with secondary dystroglycanopathies, we show that contactin-1 is abnormally localized to the sarcolemma instead of exclusively at the NMJ. The cntn1 null mouse presents with ataxia, progressive muscle weakness, and postnatal lethality, similar to the affected members in this family. We propose that loss of contactin-1 from the NMJ impairs communication or adhesion between nerve and muscle resulting in the severe myopathic phenotype. This disorder is part of the continuum in the clinical spectrum of congenital myopathies and congenital myasthenic syndromes.

  5. A syndrome of congenital retinal dystrophy and saccade palsy--a subset of Leber's amaurosis.

    PubMed Central

    Moore, A. T.; Taylor, D. S.

    1984-01-01

    Three children who presented in infancy with a severe visual defect and absent or barely recordable electroretinograms, with relatively well preserved visually evoked cortical potentials, were subsequently found to have vertical and horizontal saccade palsies with head thrusts but relatively good visual acuity. These children, who were clearly different from other infants with congenital retinal dystrophy, were also developmentally delayed and had systemic motor and speech defects, but their visual prognosis was relatively good. The recognition of their saccade palsy was delayed because their poor visual attention in infancy was ascribed purely to the tapetoretinal degeneration. We consider these patients represent a clear subset of those patients who are diagnosed as having congenital retinal dystrophy or Leber's amaurosis. Images PMID:6722075

  6. A syndrome of congenital retinal dystrophy and saccade palsy--a subset of Leber's amaurosis.

    PubMed

    Moore, A T; Taylor, D S

    1984-06-01

    Three children who presented in infancy with a severe visual defect and absent or barely recordable electroretinograms, with relatively well preserved visually evoked cortical potentials, were subsequently found to have vertical and horizontal saccade palsies with head thrusts but relatively good visual acuity. These children, who were clearly different from other infants with congenital retinal dystrophy, were also developmentally delayed and had systemic motor and speech defects, but their visual prognosis was relatively good. The recognition of their saccade palsy was delayed because their poor visual attention in infancy was ascribed purely to the tapetoretinal degeneration. We consider these patients represent a clear subset of those patients who are diagnosed as having congenital retinal dystrophy or Leber's amaurosis.

  7. Video-assisted thoracoscopic extended thymectomy in myasthenic children

    PubMed Central

    Sonzogni, Rita; Novellino, Lorenzo; Benigni, Alberto; Busi, Ilaria; Khotcholava, Magda; Spotti, Angelica; Sonzogni, Valter

    2013-01-01

    Myasthenia gravis (MG) is an autoimmune disease marked by weakness of voluntary musculature. Medical and surgical therapy of adult myasthenia is well documented. There is little pediatric surgical evidence, only a few case reports being available. The aim of this paper is to verify whether the surgical and anesthesiological techniques can warrant an early and safe discharge from the operating room. The secondary aim is to assess the presence of perioperative indicators that can eventually be used as predictors of postoperative care. During the years 2006–2009, 10 pediatric patients were treated according to a surgical approach based on video assisted thoracoscopic extended thymectomy (VATET). Standard preoperative evaluation is integrated with functional respiratory tests. Anesthetic induction was made with propofol and fentanyl/remifentanyl and maintenance was obtained with sevoflurane/desflurane/propofol ± remifentanyl. A muscle relaxant was used in only one patient. Right or left double-lumen bronchial tube (Rüsch Bronchopart® Carlens) placement was performed. Six patients were transferred directly to the surgical ward while 4 were discharged to the intensive care unit (ICU); ICU stay was no longer than 24 h. Length of hospital stay was 4.4±0.51 days. No patient was readmitted to the hospital and no surgical complications were reported. Volatile and intravenous anesthetics do not affect ventilator weaning, extubation or the postoperative course. Paralyzing agents are not totally contraindicated, especially if short-lasting agents are used with neuromuscular monitoring devices and new reversal drugs. Perioperative evaluation of the myasthenic patient is mandatory to assess the need for postoperative respiratory support and also predict timely extubation with early transfer to the surgical department. Availability of new drugs and of reversal drugs, the current practice of mini-invasive surgical techniques, and the availability of post anesthesia care units

  8. Rituximab treatment for recurrence of nephrotic syndrome in a pediatric patient after renal transplantation for congenital nephrotic syndrome of Finnish type.

    PubMed

    Chaudhuri, Abanti; Kambham, Neeraja; Sutherland, Scott; Grimm, Paul; Alexander, Steven; Concepcion, Waldo; Sarwal, Minnie; Wong, Cynthia

    2012-08-01

    Congenital nephrotic syndrome (CNS) of the Finnish type due to mutation in the NPHS-1 gene results in massive proteinuria due to structural abnormality in the glomerular slit diaphragm, and is usually refractory to immunosuppressive therapy. Patients eventually require bilateral nephrectomy and renal replacement therapy, with transplantation being the ultimate goal. Post-transplant recurrence of nephrotic syndrome occurs in about 25% of children and is thought to be immune-mediated secondary to antibodies formed against the nephrin protein in renal allograft. Conventional therapy with calcineurin inhibitors (CNI), cyclophosphamide and corticosteroids with or without plasmapheresis often fails to achieve remission resulting in graft loss in 12-16%. There is limited experience with use of rituximab (RTX) in pediatric organ transplant recipients. We report the first case of post-transplant recurrence of nephrotic syndrome in a 4-yr-old child with CNS due to NPHS-1 mutation in whom CNI, corticosteroid and cyclophosphamide therapy was unsuccessful, but who achieved remission after depletion of B cells with RTX, associated with a decrease in the level of anti-nephrin antibodies. The child remains in remission 5 yr following treatment. Our experience suggests that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation in children with CNS.

  9. Congenital Clasped Thumb That Is Forgetten a Syndrome in Clinical Practice

    PubMed Central

    Serbest, Sancar; Tosun, Haci Bayram; Tiftikci, Ugur; Gumustas, Seyit Ali; Uludag, Abuzer

    2015-01-01

    Abstract Congenital clasped thumb is a progressive flexion and adduction deformity presenting with heterogeneous congenital anomalies. Although the disease is rare, diagnosis is usually delayed due to natural location of thumb within the palm in first 3 months of life. A 4-year-old girl with congenital clasped thumb deformity due to absence of extensor pollicis brevis tendon whose treatment consisted of extensor indicis proprius (EIP) transfer and z-plasty reconstruction to first web space. The patient was so happy with both cosmetic appearance and functional status. There was not any limitation at interphalangeal or metacarpophalangeal (MCP) joints of the thumb and the result was. Stability of MCP joint was full and power for grasping any object was much better than the original status. In cases of isolated clasped thumb deformity associated with absence of tendon whose treatment attempts with splinting and physical treatment have failed, EIP tendon transfer and reconstruction of contracture in first web space with z-plasty is an easy and successful method to obtain functional improvement. PMID:26402835

  10. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    PubMed Central

    Reveiz, Ludovic; Oladapo, Olufemi T.; Martínez-Vega, Ruth; Haefliger, Anina

    2017-01-01

    Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the

  11. Beals syndrome (congenital contractural arachnodactyly): prenatal ultrasound findings and molecular analysis.

    PubMed

    Inbar-Feigenberg, M; Meirowitz, N; Nanda, D; Toi, A; Okun, N; Chitayat, D

    2014-10-01

    We report the prenatal findings in two cases of Beals syndrome. Both pregnancies presented with clinical features of arthrogryposis multiplex congenita/fetal akinesia syndrome (AMC/FAS), including clenched fists and multiple joint contractures on repeat prenatal ultrasound examinations. The first case was diagnosed as having Beals syndrome on physical examination shortly after birth and the diagnosis was confirmed by DNA analysis, shown as a point mutation in the fibrillin 2 (FBN2) gene. The second case was diagnosed with Beals syndrome following microarray analysis on amniocytes, which showed a deletion of the FBN2 gene. Although most cases with AMC/FAS carry a poor prognosis, Beals syndrome is consistent with normal cognitive development and a better prognosis. Thus, making the correct diagnosis is crucial, both pre- and postnatally, for accurate counseling and management.

  12. Prenatal Diagnosis of Walker-Warburg Syndrome Using Single Nucleotide Polymorphism Array: A Clinical Experience from Three Related Palestinian Families with Congenital Hydrocephalus.

    PubMed

    Abumansour, Iman S; Al Sulmi, Eman; Chodirker, Bernard N; Hunt, Jennifer C

    2015-10-01

    Background Congenital hydrocephalus is a common and often disabling disorder. Various syndromic forms of hydrocephalus have been reported in the Palestinian population including Walker-Warburg syndrome (WWS), Carpenter syndrome, and Meckel syndrome. Aim In this report we discuss the antenatal diagnosis of congenital hydrocephalus in three related Palestinian families. Method Single nucleotide polymorphism (SNP) array was performed prenatally for the third affected fetus. Results A diagnosis of WWS was found and molecular testing revealed a known pathogenic mutation in the POMT2 gene. An affected fetus from the other family was diagnosed and tested postnatally in light of this finding. Testing of another affected stillborn offspring was performed and revealed the same mutation. Conclusions Here, we show that the use of prenatal SNP array testing can be helpful in elucidating the etiology of congenital hydrocephalus and in guiding appropriate perinatal care. Also, testing for this specific POMT2 mutation should be considered in cases of prenatally detected hydrocephalus in Palestinian families.

  13. Leber's congenital amaurosis associated with familial juvenile nephronophthisis and cone-shaped epiphyses of the hands (the Saldino-Mainzer syndrome).

    PubMed

    Ellis, D S; Heckenlively, J R; Martin, C L; Lachman, R S; Sakati, N A; Rimoin, D L

    1984-02-01

    Three affected children (a 13-year-old girl and her 7- and 8-year-old brothers) in a sibship of eight had findings consistent with the Saldino-Mainzer syndrome (skeletal dysplasia associated with Leber's congenital amaurosis, familial juvenile nephronophthisis, and cone-shaped epiphyses of the hands). Two also had pigmented midline nevi. Although tapetoretinal degeneration and familial juvenile nephronophthisis are associated in the inherited Senior-Loken syndrome, the rare association of these abnormalities with cone-shaped epiphyses of the hands suggested an autosomal recessive syndrome with variable expression remarkably similar to the Saldino-Mainzer syndrome, which may or may not be distinct from the Senior-Loken syndrome. The association of tapetoretinal degeneration with skeletal dysplasia may indicate asymptomatic renal or hepatic disease.

  14. Congenital scoliosis.

    PubMed

    Kose, Nusret; Campbell, Robert M

    2004-05-01

    The management of congenital scoliosis requires a systematic approach with careful attention to detail. Any fortuitous diagnosis of vertebral anomalies in infancy, even if there is no significant scoliosis at that time on x-ray, requires frequent clinical and radiographic follow-up to detect progression. The presence of associated anomalies of the spinal cord, the kidneys and the heart should be evaluated by MRI, renal ultrasound or IVP, with cardiology evaluation as indicated. Curve progression or severe vertebral anomalies known to cause curve progression require immediate treatment to prevent deformity. Significant thoracic deformity, especially in a patient with thoracic insufficiency syndrome, is best treated with expansion thoracoplasty. The patient with congenital scoliosis requires a long term commitment to care with frequent orthopaedic follow-up throughout the growing years along with routine pulmonary function assessment once the patient is able to cooperate with testing.

  15. Multiple congenital malformations in two sibs reminiscent of hydrolethalus and pseudotrisomy 13 syndromes

    SciTech Connect

    Dincsoy, M.Y.; Salih, M.A.M.; Al-Jurayyan, N.

    1995-04-10

    We report on two sibs, born to consanguineous parents, with defects of the midline including cleft lip and palate, flat nose, hypotelorism, and dysgenesis of corpus callosum, in addition to short limbs, radiolucent tibial notch, digital anomalies, ambiguous genitalia, and hypopituitarism. In spite of the similarities between this condition and the hydrolethalus and pseudotrisomy 13 syndromes, our patients had neither preaxial nor postaxial polydactyly, but had previously undescribed bilateral radiolucent tibial notch, which is not known to be part of those two syndromes. The cases presented here may very well represent a new autosomal recessive syndrome. 20 refs., 4 figs., 1 tab.

  16. A Case of Lacrimo-Auriculo-Dento-Digital Syndrome with Multiple Congenitally Missing Teeth

    PubMed Central

    Krishna, Munagala Karthik; Rallan, Mandeep

    2016-01-01

    Lacrimo-auriculo-dento-digital (LADD) syndrome is an extremely rare disorder which may occur sporadically or inheritably as an autosomal dominant condition. It is characterized by defects in the lacrimal apparatus, ear problems, and dental and digital abnormalities. However, specific symptoms vary greatly among the cases with a high degree of overlap with other similar genetic disorders. Here, we describe a 7-year-old boy with LADD syndrome, clinical and radiological findings, dental treatment undertaken, and its differential diagnosis. PMID:27803819

  17. Identification of a Novel Mutation in BRD4 that Causes Autosomal Dominant Syndromic Congenital Cataracts Associated with Other Neuro-Skeletal Anomalies

    PubMed Central

    Jin, Hyun-Seok; Kim, Jeonhyun; Kwak, Woori; Jeong, Hyeonsoo; Lim, Gyu-Bin

    2017-01-01

    Congenital cataracts can occur as a non-syndromic isolated ocular disease or as a part of genetic syndromes accompanied by a multi-systemic disease. Approximately 50% of all congenital cataract cases have a heterogeneous genetic basis. Here, we describe three generations of a family with an autosomal dominant inheritance pattern and common complex phenotypes, including bilateral congenital cataracts, short stature, macrocephaly, and minor skeletal anomalies. We did not find any chromosomal aberrations or gene copy number abnormalities using conventional genetic tests; accordingly, we conducted whole-exome sequencing (WES) to identify disease-causing genetic alterations in this family. Based on family WES data, we identified a novel BRD4 missense mutation as a candidate causal variant and performed cell-based experiments by ablation of endogenous BRD4 expression in human lens epithelial cells. The protein expression levels of connexin 43, p62, LC3BII, and p53 differed significantly between control cells and cells in which endogenous BRD4 expression was inhibited. We inferred that a BRD4 missense mutation was the likely disease-causing mutation in this family. Our findings may improve the molecular diagnosis of congenital cataracts and support the use of WES to clarify the genetic basis of complex diseases. PMID:28076398

  18. Pathology of parainfluenza virus infection in patients with congenital immunodeficiency syndromes.

    PubMed

    Madden, John F; Burchette, James L; Hale, Laura P

    2004-05-01

    Infection with parainfluenza virus typically produces a mild, self-limited upper respiratory infection. However, parainfluenza infections have become increasingly recognized as a source of severe morbidity and mortality in immunocompromised patients. In this retrospective study we identified 6 patients with congenital immunodeficiency and positive respiratory cultures for parainfluenza virus who died and underwent complete autopsy. Tissues obtained at autopsy were studied using hematoxylin and eosin-stained sections, immunoperoxidase staining for parainfluenza virus, and in selected cases, electron microscopy. All 6 patients exhibited typical cytopathic effects of parainfluenza virus, including giant cell formation, in lung and/or bronchial tissues. Parainfluenza virus infection was also documented by giant cell formation and immunohistochemistry in the pancreas (in 3 of 6 patients) and the kidney or bladder (in 2 of 4 patients). Anti-parainfluenza antibody also specifically reacted with cells in the gastrointestinal tract (in 2 of 4), spleen (in 4 of 6), thymus and/or lymph nodes (in 4 of 4), and small blood vessels in various organs (in 4 of 6). Pancreatic, bladder, colon, and thymic epithelial cell lines were susceptible to experimental infections with clinical isolates of parainfluenza virus type 3 in vitro. Parainfluenza virus infection was serious in patients with congenital immunodeficiencies, contributing directly to death in 5 of the 6 patients studied. Because this virus is capable of infecting tissues in the gastrointestinal and urinary systems as well as in the respiratory tract, body secretions and fluids from each of these locations should be considered potentially infectious.

  19. Polysplenia syndrome with congenital agenesis of dorsal pancreas presenting as acute pancreatitis and the role of endoscopic ultrasonography in its diagnosis.

    PubMed

    Jeong, Jae Hoon; Kim, Gwang Ha; Song, Geun Am; Lee, Dong Gun; Moon, Ji Yoon; Cheong, Jae Hoon; Kim, Suk

    2012-07-01

    A 49-year-old female was admitted to our hospital for acute pancreatitis. The abdomen CT scan incidentally showed midline liver with hepatomegaly, centrally located gallbladder, pancreas truncation, right sided small bowel, left sided large bowel, interruption of the inferior vena cava with azygos continuation, preduodenal portal vein, and multiple spleens in the left upper quadrant. In MRCP, the head of pancreas was enlarged and short main pancreatic duct without accessory duct was showed. EUS revealed enlarged ventral pancreas with a main pancreatic duct of normal caliber, absence of the accessory pancreatic duct and the dorsal pancreas. She was diagnosed as polysplenia syndrome with agenesis of dorsal pancreas. It is a rare congenital anomaly frequently associated with various visceral anomalies including multiple spleens, impaired visceral lateralization, congenital heart diseases, gastrointestinal abnormalities and azygos continuation of the inferior vena cava. We report a case of polysplenia syndrome with agenesis of dorsal pancreas presenting acute pancreatitis.

  20. Microdeletion on 17p11.2 in a Smith-Magenis syndrome patient with mental retardation and congenital heart defect: first report from China.

    PubMed

    Huang, C; Yang, Y-F; Zhang, H; Xie, L; Chen, J-L; Wang, J; Tan, Z-P; Luo, H

    2012-08-13

    Smith-Magenis syndrome (SMS) is a rare syndrome with multiple congenital malformations, including development and mental retardation, behavioral problems and a distinct facial appearance. SMS is caused by haploinsufficiency of RAI1 (deletion or mutation of RAI1). We describe an eight-year-old female Chinese patient with multiple malformations, congenital heart defect, mental retardation, and behavioral problems (self hugging, sleeping disturbance). High-resolution genome wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in chromosome region 17p11.2. This chromosome region contains RAI1, a critical gene involved in SMS. To the best of our knowledge, this is the first report of an SMS patient in mainland China.

  1. Fetoscopic and ultrasound-guided decompression of the fetal trachea in a human fetus with Fraser syndrome and congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia.

    PubMed

    Kohl, T; Hering, R; Bauriedel, G; Van de Vondel, P; Heep, A; Keiner, S; Müller, A; Franz, A; Bartmann, P; Gembruch, U

    2006-01-01

    Congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia bears a poor prognosis for hydropic fetuses owing to cardiac failure. We attempted percutaneous fetoscopic and ultrasound-guided tracheal decompression in a hydropic human fetus with CHAOS associated with Fraser syndrome. Percutaneous fetoscopic and ultrasound-guided tracheal decompression was performed using three trocars under general materno-fetal anesthesia at 19 + 5 weeks of gestation. Abnormal fetoplacental blood flow normalized within hours as a result of the intervention. Furthermore, a normalization of lung : heart size and lung echogenicity was observed within days. Resolution of hydrops was complete within 3 weeks. Premature rupture of membranes and premature contractions prompted emergency delivery of the fetus by ex-utero intrapartum treatment (EXIT) at 28 + 2 weeks of gestation. Following delivery, the lungs could be ventilated at low pressures and ambient oxygen concentration. Weaning from ventilation was achieved at 18 days of postnatal life. Our experience indicated that percutaneous fetoscopic and ultrasound-guided decompression of the fetal trachea is feasible and may permit normalization of hemodynamics in hydropic human fetuses with CHAOS from laryngeal atresia. The procedure may also result in normalization of heart : lung size and provide the time needed to regain the function of the overstretched diaphragm in this grave fetal condition.

  2. A very rare case of polysplenia syndrome with congenital diffuse pulmonary arteriovenous fistulas.

    PubMed

    Gürses, Dolunay; Ulger, Zülal; Levent, Ertürk; Ozyürek, A Ruhi

    2006-01-01

    A five-year-old girl patient was admitted with cyanosis and dyspnea, which started from birth. She had small telangiectatic lesions on her face and cerebral arteriovenous malformation, but no family history of hereditary hemorrhagic telangiectasia. Contrast echocardiography and pulmonary angiography demonstrated diffuse pulmonary arteriovenous fistulas. The patient was diagnosed as polysplenia syndrome characterized with left atrial isomerism, interrupted inferior vena cava, azygous continuation to the superior vena cava, and hepatic veins draining to the right atrium. In contrast to the other polysplenia syndrome cases, in this patient, pulmonary arteriovenous fistulas were not associated with cavopulmonary anastomoses or liver disease.

  3. Genetics of congenital hypothyroidism

    PubMed Central

    Park, S; Chatterjee, V

    2005-01-01

    Congenital hypothyroidism is the most common neonatal metabolic disorder and results in severe neurodevelopmental impairment and infertility if untreated. Congenital hypothyroidism is usually sporadic but up to 2% of thyroid dysgenesis is familial, and congenital hypothyroidism caused by organification defects is often recessively inherited. The candidate genes associated with this genetically heterogeneous disorder form two main groups: those causing thyroid gland dysgenesis and those causing dyshormonogenesis. Genes associated with thyroid gland dysgenesis include the TSH receptor in non-syndromic congenital hypothyroidism, and Gsα and the thyroid transcription factors (TTF-1, TTF-2, and Pax-8), associated with different complex syndromes that include congenital hypothyroidism. Among those causing dyshormonogenesis, the thyroid peroxidase and thyroglobulin genes were initially described, and more recently PDS (Pendred syndrome), NIS (sodium iodide symporter), and THOX2 (thyroid oxidase 2) gene defects. There is also early evidence for a third group of congenital hypothyroid conditions associated with iodothyronine transporter defects associated with severe neurological sequelae. This review focuses on the genetic aspects of primary congenital hypothyroidism. PMID:15863666

  4. Additional case of Neuhäuser megalocornea and mental retardation syndrome with congenital hypotonia.

    PubMed

    Santolaya, J M; Grijalbo, A; Delgado, A; Erdozaín, G

    1992-06-01

    We report on a 3-1/2-year-old Spanish girl with the Neuhäuser megalocornea and mental retardation syndrome. A review shows that megalocornea, mental retardation, and, presumably, hypotonia, are the major manifestations for diagnosis. The facial appearance of the typical cases is characterised by frontal bossing, broad nasal bridge, mild hypertelorism, long upper lip, and small mandible.

  5. Reversible acquired epileptic frontal syndrome and CSWS suppression in a child with congenital hemiparesis treated by hemispherotomy.

    PubMed

    Kallay, Christine; Mayor-Dubois, Claire; Maeder-Ingvar, Malin; Seeck, Margritta; Debatisse, Damien; Deonna, Thierry; Roulet-Perez, Eliane

    2009-09-01

    A boy with a right congenital hemiparesis due to a left pre-natal middle cerebral artery infarct developed focal epilepsy at 33 months and then an insidious and subsequently more rapid, massive cognitive and behavioural regression with a frontal syndrome between the ages of 4 and 5 years with continuous spike-waves during sleep (CSWS) on the EEG. Both the epilepsy and the CSWS were immediately suppressed by hemispherotomy at the age of 5 years and 4 months. A behavioural-cognitive follow-up prior to hemispherotomy, an per-operative EEG and corticography and serial post-operative neuropsychological assessments were performed until the age of 11 years. The spread of the epileptic activity to the "healthy" frontal region was the cause of the reversible frontal syndrome. A later gradual long-term but incomplete cognitive recovery, with moderate mental disability was documented. This outcome is probably explained by another facet of the epilepsy, namely the structural effects of prolonged epileptic discharges in rapidly developing cerebral networks which are, at the same time undergoing the reorganization imposed by a unilateral early hemispheric lesion. Group studies on the outcome of children before and after hemispherectomy using only single IQ measures, pre- and post-operatively, may miss particular epileptic cognitive dysfunctions as they are likely to be different from case to case. Such detailed and rarely available complementary clinical and EEG data obtained in a single case at different time periods in relation to the epilepsy, including per-operative electrophysiological findings, may help to understand the different cognitive deficits and recovery profiles and the limits of full cognitive recovery.

  6. A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A.

    PubMed

    Fine, Dina; Flusser, Hagit; Markus, Barak; Shorer, Zamir; Gradstein, Libe; Khateeb, Shareef; Langer, Yshia; Narkis, Ginat; Birk, Ruth; Galil, Aharon; Shelef, Ilan; Birk, Ohad S

    2015-12-01

    A consanguineous Bedouin Israeli kindred presented with a novel autosomal recessive intellectual disability syndrome of congenital microcephaly, low anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and tented thick eyebrows with sparse hair in their medial segment. Brain imaging demonstrated various degrees of agenesis of corpus callosum and hypoplasia of the vermis and cerebellum. Genome-wide linkage analysis followed by fine mapping defined a 7.67 Mb disease-associated locus (LOD score 4.99 at θ=0 for marker D10S1653). Sequencing of the 48 genes within the locus identified a single non-synonymous homozygous duplication frameshift mutation of 13 nucleotides (c.2134_2146dup13) within the coding region of FRMD4A, that was common to all affected individuals and not found in 180 non-related Bedouin controls. Three of 50 remotely related healthy controls of the same tribe were heterozygous for the mutation. FRMD4A, member of the FERM superfamily, is involved in cell structure, transport and signaling. It regulates cell polarity by playing an important role in the activation of ARF6, mediating the interaction between Par3 and the ARF6 guanine nucleotide exchange factor. ARF6 is known to modulate cell polarity in neurons, and regulates dendritic branching in hippocampal neurons and neurite outgrowth. The FRMD4 domain that is essential for determining cell polarity through interaction with Par3 is truncated by the c.2134_2146dup13 mutation. FRMD4A polymorphisms were recently suggested to be a risk factor for Alzheimer's disease. We now show a homozygous frameshift mutation of the same gene in a severe neurologic syndrome with unique dysmorphism.

  7. Is congenital melanocytic naevus a link between Hirayama disease and moyamoya pattern: a new syndrome or a co-incidence?

    PubMed

    Puri, Inder; Vibha, Deepti; Prasad, Kameshwar; Bhatia, Rohit

    2016-01-08

    A 22-year-old man presented with a history of progressive weakness and wasting of the right hand and forearm for 12 months followed by similar symptoms in the left upper limb for the past 5 months. He also gave a history of episodes of loss of consciousness for the past 5 years with a frequency of one per 3 months. On examination, there were melanocytic naevi-one large lesion in the nape of the neck and multiple satellite lesions. On investigation, the cervical cord MRI was normal. The brain MRI and angiography showed a moyamoya pattern. Thus, this patient had congenital melanocytic naevi with Hirayama disease and moyamoya pattern. He was treated with extracranial-intracranial bypass for moyamoya disease. During 6-month follow-up, he has been stable. Although moyamoya syndrome has been associated with several systemic diseases and conditions, the coexistence of a moyamoya pattern with Hirayama disease and melanocytic naevi has not been described so far.

  8. Epidemiological characteristics of rubella and congenital rubella syndrome in the 2012-2013 epidemics in Tokyo, Japan.

    PubMed

    Sugishita, Yoshiyuki; Shimatani, Naotaka; Katow, Shigetaka; Takahashi, Takuri; Hori, Narumi

    2015-01-01

    A large rubella outbreak has been observed since June 2012 in Tokyo, Japan, and a rapid increase in the number of congenital rubella syndrome (CRS) cases have also been reported in Japan since October 2012. All the clinically diagnosed and laboratory-confirmed rubella cases reported in Tokyo from January 2012 to December 2013 and all the laboratory-confirmed CRS cases from January 2012 to March 2014 were analyzed. In total, 4,116 rubella cases were reported in Tokyo. Of these, 77.2% (n=3,176) were male; the highest number of cases occurred in males aged 35-39 years and in females aged 20-24 years. Complications included arthralgia/arthritis (19.4%), thrombocytopenic purpura (0.5%), hepatic dysfunction (0.3%), and encephalitis (0.1%). The circulating rubella virus in Tokyo was genotype 2B. The most possible site of transmission was the workplace. Because of the rubella epidemic, 16 CRS cases were reported in Tokyo from March 2013 to February 2014. Domestic infection with rubella was proven for all mothers of 16 cases. This situation suggests that Japan is still working to achieve rubella elimination.

  9. Sonographic Diagnosis in a Rare Aetiology of Neonatal Scrotal Swellings: A Case Report of Congenital Nephrotic Syndrome

    PubMed Central

    Grover, Shabnam Bhandari; Kumar, Nishith; Grover, Hemal; Taneja, Dinesh Kumar; Katyan, Amit

    2016-01-01

    Summary Background Common etiologies of scrotal swelling in neonates include hydrocoele, inguinal hernia and testicular torsion; less common is epididymo-orchitis. Congenital nephrotic syndrome (CNS), a rare entity, is known to present as progressive renal failure and its leading presentation with scrotal involvement has not been reported. Material/Methods We report a rare case of CNS with primary clinical presentation as scrotal cellulitis and epididymo-orchitis. In this neonate, scrotal and abdominal ultrasound examination was performed and the laboratory data were obtained. Results Sonography revealed bilaterally enlarged echogenic kidneys, testis and epididymis with echogenic peritoneal fluid tracking into both scrotal sacs. Laboratory data revealed proteinuria and severe depletion of serum IgG. Culture of the peritoneal fluid showed gram-negative organisms. A final diagnosis of CNS, complicated with peritonitis tracking into the scrotal sacs was arrived at. Conclusions CNS may have a rare presentation with distracting symptoms of scrotal cellulitis and epididymo-orchitis, as seen in our patient. However, diligent use of abdomino-scrotal sonography, supported by relevant laboratory data can clinch the accurate diagnosis. PMID:27757175

  10. Identification of altered pathways in Down syndrome-associated congenital heart defects using an individualized pathway aberrance score.

    PubMed

    Chen, Y Q; Li, T; Guo, W Y; Su, F J; Zhang, Y X

    2016-04-26

    The aim of this study was to identify disrupted pathways related to Down syndrome (DS), and DS-associated congenital heart defects (DS-CHD). The gene expression profile and pathway data of 10 human DS patients and 5 control samples in E-GEOD-1789 were recruited and analyzed by the individualized pathway aberrance score (iPAS) method, consisting of the data processing, gene-level statistics, pathway-level statistics, and significant measurement steps. The pre-processing step identified 12,493 genes and 1022 pathways (4269 genes). The pathway significant analysis identified eight pathways (adjusted P value <0.1) that differed between the disease and control samples. The cross-presentation of particulate exogenous antigen (phagosomes) and methionine salvage pathways showed the most significant differences among these. The gene expression levels of key pathway genes, such as CYBB and ADI1, were higher in disease samples than in normal controls. Based on our results, we predicted that the cross-presentation of particulate exogenous antigens (phagosomes) and the methionine salvage pathway could be good indicators of DS-CHD.

  11. Induction of Podocyte VEGF164 Overexpression at Different Stages of Development Causes Congenital Nephrosis or Steroid-Resistant Nephrotic Syndrome

    PubMed Central

    Veron, Delma; Reidy, Kimberly; Marlier, Arnaud; Bertuccio, Claudia; Villegas, Guillermo; Jimenez, Juan; Kashgarian, Michael; Tufro, Alda

    2010-01-01

    The tight regulation of vascular endothelial growth factor-A (VEGF-A) signaling is required for both the development and maintenance of the glomerular filtration barrier, but the pathogenic role of excessive amounts of VEGF-A detected in multiple renal diseases remains poorly defined. We generated inducible transgenic mice that overexpress podocyte VEGF164 at any chosen stage of development. In this study, we report the phenotypes that result from podocyte VEGF164 excess during organogenesis and after birth. On doxycycline induction, podocin-rtTA:tet-O-VEGF164 mice express twofold higher kidney VEGF164 levels than single transgenic mice, localized to podocytes. Podocyte VEGF164 overexpression during organogenesis resulted in albuminuria at birth and was associated with glomerulomegaly, uniform podocyte effacement, very few and wide foot processes joined by occluding junctions, almost complete absence of slit diaphragms, and swollen endothelial cells with few fenestrae as revealed by transmission electron microscopy. Podocyte VEGF164 overexpression after birth caused massive albuminuria in 70% of 2-week-old mice, glomerulomegaly, and minimal changes on light microscopy. Transmission electron microscopy showed podocyte effacement and fusion and morphologically normal endothelial cells. Podocyte VEGF164 overexpression induced nephrin down-regulation without podocyte loss. VEGF164-induced abnormalities were reversible on removal of doxycycline and were unresponsive to methylprednisolone. Collectively, the data suggest that moderate podocyte VEGF164 overexpression during organogenesis results in congenital nephrotic syndrome, whereas VEGF164 overexpression after birth induces a steroid-resistant minimal change like-disease in mice. PMID:20829436

  12. Therapeutic abortions following rubella infection in pregnancy: the potential impact on the incidence of congenital rubella syndrome.

    PubMed Central

    Serdula, M K; Marks, J S; Herrmann, K L; Orenstein, W A; Hall, A D; Bomgaars, M R

    1984-01-01

    In 1977, a large rubella outbreak occurred in Hawaii. Because attack rates were high among women of childbearing age, we conducted extensive surveillance efforts to detect both pregnancies complicated by rubella and cases of congenital rubella syndrome (CRS). Initial surveillance included a survey of physicians and hospitals, review of fetal death and birth certificates, and cord blood screening for rubella-specific IgM of infants born following the epidemic. Two years after the outbreak, the medical community was again surveyed to identify affected children who were missed initially. No case of CRS was identified either shortly after the outbreak or in the ensuing two years. In addition, none of the 5,605 cord serum samples obtained was found to contain rubella-specific IgM antibody. Through active surveillance, we received 12 reports of rubella in pregnant women, of whom 11 elected to terminate their pregnancies. The extensive use of therapeutic abortion by exposed women may have prevented the birth of infants with CRS. Surveillance for rubella-related abortions is an important component in assessing the health impact of rubella in a community. PMID:6496818

  13. Congenital Central Hypoventilation Syndrome and the PHOX2B Gene: A Model of Respiratory and Autonomic Dysregulation

    PubMed Central

    Patwari, Pallavi P.; Carroll, Michael S.; Rand, Casey M.; Kumar, Rajesh; Harper, Ronald M.; Weese-Mayer, Debra E.

    2010-01-01

    The paired-like homeobox 2B gene (PHOX2B) is the disease-defining gene for congenital central hypoventilation syndrome (CCHS). Individuals with CCHS typically present in the newborn period with alveolar hypoventilation during sleep and often during wakefulness, altered respiratory control including reduced or absent ventilatory responses to hypercarbia and hypoxemia, and autonomic nervous system (ANS) dysregulation; however, a subset of individuals present well into adulthood. Thermoregulation is altered and perception of shortness of breath is absent, but voluntary breathing is retained. Structural and functional magnetic resonance imaging (MRI) and limited post-mortem studies in subjects with CCHS reveal abnormalities in both forebrain and brainstem. MRI changes appear in the hypothalamus (responsible for thermal drive to breathing), posterior thalamus and midbrain (mediating O2 and oscillatory motor patterns), caudal raphé and locus coeruleus (regulating serotonergic and noradrenergic systems), the lateral medulla, parabrachial pons, and cerebellum (coordinating chemoreceptor and somatic afferent activity with breathing), and insular and cingulate cortices (mediating shortness of breath perception). Structural and functional alterations in these sites may result from PHOX2B mutations or be secondary to hypoxia/perfusion alterations from suboptimal management/compliance. The study of CCHS, with collaboration between physician-scientists and basic scientists, offers a rare opportunity to investigate control of breathing within the complex physiological network of the ANS. PMID:20601214

  14. Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract.

    PubMed

    Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hilger, Alina C; Saisawat, Pawaree; Vivante, Asaf; Stajic, Natasa; Bogdanovic, Radovan; Reutter, Heiko M; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

    2014-09-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately 40% of children with ESRD in the United States. Hitherto, mutations in 23 genes have been described as causing autosomal dominant isolated CAKUT in humans. However, >90% of cases of isolated CAKUT still remain without a molecular diagnosis. Here, we hypothesized that genes mutated in recessive mouse models with the specific CAKUT phenotype of unilateral renal agenesis may also be mutated in humans with isolated CAKUT. We applied next-generation sequencing technology for targeted exon sequencing of 12 recessive murine candidate genes in 574 individuals with isolated CAKUT from 590 families. In 15 of 590 families, we identified recessive mutations in the genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1, all of which function in the interaction of the ureteric bud and the metanephric mesenchyme. We show that isolated CAKUT may be caused partially by mutations in recessive genes. Our results also indicate that biallelic missense mutations in the Fraser/MOTA/BNAR spectrum genes cause isolated CAKUT, whereas truncating mutations are found in the multiorgan form of Fraser syndrome. The newly identified recessive biallelic mutations in these six genes represent the molecular cause of isolated CAKUT in 2.5% of the 590 affected families in this study.

  15. Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 1: Burden of disease from CRS.

    PubMed Central

    Cutts, F. T.; Robertson, S. E.; Diaz-Ortega, J. L.; Samuel, R.

    1997-01-01

    Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and cataracts, and a variety of other permanent manifestations. In developing countries, the burden of CRS has been assessed as follows: by surveillance of CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by serosurveys documenting the rubella susceptibility of women of childbearing age. During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported from industrialized countries during the pre-vaccine era. Special studies of CRS have been reported from all WHO regions. Rubella surveillance data show that epidemics occur every 4-7 years, similar to the situation in Europe during the pre-vaccination era. In developing countries, the estimated average age at infection varies from 2-3 years to 8 years. For 45 developing countries we identified serosurveys of women of childbearing age that had enrolled > or = 100 individuals. The proportion of women who remained susceptible to rubella (e.g. seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25% in 12 countries. Discussed are methods to improve the surveillance of rubella and CRS in developing countries. PMID:9141751

  16. Syndrome-Related Stigma in the General Social Environment as Reported by Women with Classical Congenital Adrenal Hyperplasia.

    PubMed

    Meyer-Bahlburg, Heino F L; Reyes-Portillo, Jazmin A; Khuri, Jananne; Ehrhardt, Anke A; New, Maria I

    2017-02-01

    Stigma defined as "undesired differentness" (Goffman, 1963) and subtyped as "experienced" or "enacted," "anticipated," and "internalized" has been documented for patients with diverse chronic diseases. However, no systematic data exist on the association of stigma with somatic intersexuality. The current report concerns women with classical congenital adrenal hyperplasia (CAH), the most prevalent intersex syndrome, and provides descriptive data on CAH-related stigma as experienced in the general social environment (excluding medical settings and romantic/sexual partners) during childhood, adolescence, and adulthood. A total of 62 adult women with classical CAH [41 with the salt-wasting (SW) variant and 21 with the simple-virilizing (SV) variant] underwent a qualitative retrospective interview, which focused on the impact of CAH and its medical treatment on many aspects of women's lives. Deductive content analysis was performed on the transcribed texts. The women's accounts of CAH-related stigma were identified and excerpted as vignettes, and the vignettes categorized according to social context, stigma type, and the associated features of the CAH condition. Nearly two-thirds of women with either variant of CAH provided stigma vignettes. The vignettes included all three stigma types, and most involved some somatic or behavioral feature related to sex or gender. Stigma situations were reported for all ages and all social contexts of everyday life: family, peers, colleagues at work, strangers, and the media. We conclude that there is a need for systematic documentation of stigma in intersexuality as a basis for the development of improved approaches to prevention and intervention.

  17. Enhanced A-V nodal conduction (Lown-Ganong-Levine syndrome) by congenitally hypoplastic A-V node.

    PubMed

    Ometto, R; Thiene, G; Corrado, D; Vincenzi, M; Rossi, L

    1992-11-01

    The basic anatomical substrate of enhanced A-V nodal conduction, manifesting or not as Lown-Ganong-Levine syndrome, is still a controversial issue. We describe the case of a 34-year-old man who presented episodes of ventricular fibrillation. Electrophysiological studies showed that the AH interval was 55 ms, and increased by only 20 ms at paced cycle lengths of 300 ms; atrial pacing induced atrial fibrillation, with a shortest RR interval of 240 ms. Despite verapamil therapy, this patient died suddenly at home. Histological study disclosed a severe A-V node hypoplasia that was evidently congenital in nature; the rest of the conduction system was normal, and no accessory A-V pathways were present. We suggest that enhanced A-V nodal conduction in this patient was due to the developmental defect in the A-V node; this abnormality caused a loss of specific impulse-delaying function, and thus allowed rapid, unfiltered atrial impulses to reach the lower A-V junction and ventricles.

  18. A model-based evaluation of the national immunization programme against rubella infection and congenital rubella syndrome in The Netherlands.

    PubMed Central

    van der Heijden, O. G.; Conyn-van Spaendonck, M. A.; Plantinga, A. D.; Kretzschmar, M. E.

    1998-01-01

    In order to improve the prevention of cases of congenital rubella syndrome in The Netherlands, in 1987 the selective vaccination strategy against rubella infection in girls was replaced by mass vaccination. This decision was supported by mathematical model analyses carried out by Van Druten and De Boo. In order to compare the predicted impact of the rubella vaccination programme with the current available data in more detail, a similar model was built. Although the model predicts elimination of the rubella virus, data show that virus circulation is still present at a higher level than expected by the model. Simulation studies indicate that import of infection and a lower vaccine effectiveness, related to possible asymptomatic reinfection of vaccinated people, could be sources contributing to the present virus circulation. Even though the number of infections is much higher than the number of reported cases of disease, limited serosurveillance data and case notification data show that females of childbearing age are well protected by immunization. PMID:10030716

  19. A case of multiple congenital anomalies in association with Rett syndrome confirmed by MECP2 mutation screening.

    PubMed

    Ellaway, C J; Badawi, N; Raffaele, L; Christodoulou, J; Leonard, H

    2001-07-01

    Rett syndrome (RTT) is a severe neurodevelopmental disorder. Apparently normal at birth, girls with RTT undergo developmental regression and acquire a neurological and behavioural phenotype that has been used to define clinical diagnostic criteria for the disorder. Recently mutations in the methyl-CpG binding protein 2 gene (MECP2), located on Xq28 have been identified in females with RTT. We report a girl whose clinical course was complicated by congenital abnormalities of the respiratory tract and gastrointestinal system. In addition neurological abnormalities were evident in the newborn period. By the age of 3 years she had developed a phenotype very suggestive of RTT, but had not demonstrated deceleration of head growth and the development of expressive language was prevented by the presence of the tracheostomy. The clinical impression of RTT was confirmed by the recent finding of a mutation in the MECP2 gene. This case report highlights the importance of considering the clinical diagnosis of RTT even in the presence of other conditions and emphasises that girls with RTT may not be normal from birth.

  20. Apheresis in high risk antiphospholipid syndrome pregnancy and autoimmune congenital heart block.

    PubMed

    Ruffatti, Amelia; Favaro, Maria; Brucato, Antonio; Ramoni, Veronique; Facchinetti, Myriam; Tonello, Marta; Del Ross, Teresa; Calligaro, Antonia; Hoxha, Ariela; Grava, Chiara; De Silvestro, Giustina

    2015-12-01

    In the first part a prospective cohort study was reported to evaluate the efficacy and safety of a treatment protocol including plasma exchange (PE) or PE plus intravenous immunoglobulins (IVIG) or immunoadsorption (IA) plus IVIG administered in addition to conventional therapy to 22 pregnant women with high-risk APS. The results indicate that PE or IA treatments administered along with IVIG and conventional antithrombotic therapy could be a valuable and safe therapeutic option in pregnant APS women with triple antiphospholipid antibody positivity along with a history of thrombosis and/or one or more severe pregnancy complications. In the second part the efficacy and safety of PE combined with IVIG and steroids were evaluated for the treatment of 10 patients with autoimmune congenital heart block (CHB) by comparing maternal features, pregnancy outcome and side effects with those of 24 CHB patients treated with steroids only. The patients treated with the combined therapy showed a statistically significant regression of 2nd degree blocks, an increase in heart rate at birth and a significantly lower prevalence of pacing in the first year of life. Moreover, no side effects were observed except for a few steroid-related events. If these results are confirmed by large-scale studies, the apheretic procedures could lead to improved outcomes in the treatment of these devastating diseases.

  1. Effects of inhaled iloprost on congenital heart disease with Eisenmenger syndrome.

    PubMed

    Yang, Song I; Chung, Wook Jin; Jung, Sung Hwan; Choi, Deok Young

    2012-06-01

    Identification of the pathophysiology associated with Eisenmenger syndrome has led to the evaluation of targeted therapies. Iloprost is one such targeted therapy used for patients with Eisenmenger syndrome. This study aimed to assess the efficacy and safety of iloprost used for patients with Eisenmenger syndrome. In this study, 12 patients with Eisenmenger syndrome (mean age, 33.2 ± 12.1 years; 75% female) started receiving iloprost 10 μg/dose administered six times a day. Of the 12 patients, 9 were classified as New York Heart Association (NYHA) functional class 3, and three were categorized as functional class 4. Changes in 6-min walk distance, NYHA functional class, oxygen saturation at resting, and results after the 6-min walk test were checked, as well as changes in right ventricle diameter and pulmonary arterial pressure shown by echocardiography. The distance during a 6-min walk increased from 255.8 ± 120.4 to 349.4 ± 134.7 m (p = 0.013), and 10 patients improved their NYHA functional class by one grade (p = 0.007). The mean resting oxygen saturation (SpO(2)) increased from 80.6 ± 14.2 to 84.9 ± 13.0% (p = 0.040), and after the 6-min walk test, it increased from 63.8 ± 22.9 to 68.8 ± 21.5% (p = 0.007). The mean right ventricle diameter during the diastolic phase changed from 53.7 ± 4.8 to 51.4 ± 3.9 mm (p = 0.068), and the mean pulmonary arterial pressure changed from 62.8 ± 13.7 to 58.9 ± 11.7 mmHg (p = 0.059). Neither death nor critical adverse effects occurred for any patients. Mild headache and dyspnea were common reports during the iloprost treatments. No patients stopped the therapy due to these adverse effects. Iloprost is well tolerated and appears to be beneficial in the management of patients with Eisenmenger syndrome.

  2. Branchio-oto-renal syndrome plus; a contiguous gene constellation of congenital anomalies?

    SciTech Connect

    Kelly, T.E.

    1994-09-01

    A term female infant was referred to the University Hospital because of respiratory distress secondary to bilateral choanal stenosis. Her examination revealed bilateral pre-auricular pits, branchial fistulae, cupped shaped ears, and bilateral athelia. She failed ABR screening; her creatinine was elevated to 1.5 mgs% and renal ultra-sonography showed reduced kidney size bilaterally. She was the product of her mother`s third pregnancy. The first produced a now normal 5 year old son. The second pregnancy was complicated by oligohydramnios and resulted in a premature delivery at 27 weeks gestation. The infant expired secondary to pulmonary hypoplasia. The mother had bilateral neurosensory deafness, pre-auricular pits, cupped shaped ears, lacrimal stenois and bilateral athelia. She wore dentures having earlier been diagnosed with dentogeneis imperfecta. She was shorter than her three normal sisters and had experienced academic problems throughout her school years. The maternal grandfather had an adult onset neurosensory hearing loss, but he and the maternal grandmother exhibited no other features of the BOR syndrome. Althelia was present only in the mother and daughter. The mother clearly has BOR syndrome transmitted to one, and possibly two, of her three offspring. The additional features of athelia, choanal stenosis and dentogenesis imperfecta are thought to represent additional autosomal dominant traits. Greenberg described an infant with athelia and choanal atresia. By family linkage studies, the BOR syndrome has been mapped to 8q13-21 with no recombination observed with loci D8S530 and D8S279. Given a normal prophase karyotype in the proband, it is speculated that a sub-microscopic deletion at 8q13-21 is the likely basis for the constellation of birth defects seen in this mother and daughter. Analysis of D8S530 and D8S279 is currently underway in this family.

  3. Congenital Abnormalities

    MedlinePlus

    ... Listen Español Text Size Email Print Share Congenital Abnormalities Page Content Article Body About 3% to 4% ... of congenital abnormalities earlier. 5 Categories of Congenital Abnormalities Chromosome Abnormalities Chromosomes are structures that carry genetic ...

  4. [An adult case of congenital Horner's syndrome with heterochromia iridis--with special reference to alteration of Horner's sign associated with development].

    PubMed

    Uyama, E; Maeda, J; Adachi, K; Yu, T C; Araki, S

    1989-10-01

    It is well known that when the Horner's syndrome is congenital, a defect in pigmentation of the iris is usual; all or part of the iris remains light brown. We reported an adult case of congenital Horner's syndrome with remission and relapse of unilateral ptosis. A 25-year-old man was admitted to our hospital for ophthalmologic surgical treatment of right ptosis. According to the patient's mother, the patient was delivered with the aid of forceps at birth, and the right ptosis was observed during the first few days of his life. At 2 to 3 years of age, his parents noted lighter color of the right eye. The right ptosis was gradually improved as he grew older. However, he developed right ptosis again with left meralgia paresthesia since eighteen age. At age 25 years, he was noted to have right ptosis, right miosis (the left pupil measured 4.5 mm in diameter and the right 3.0 mm), right heterochromia iridis with pigmented iris nevi, and left meralgia paresthesia . Laboratory data of urine, blood and CSF as well as radiological studies of chest X-ray, skull X-ray, spine X-ray, brain MRI and spinal cord MRI showed unremarkable. Sweating test was intact, pharmacologic test to Horner's syndrome with 5% cocaine and 1.25% 1-epinephrine indicated that the damage was pointed to the post ganglionic sympathetic neuron. Ten patients with congenital Horner's syndrome reported in Japan since 1953 were reviewed including our case. Ten of eleven were male and Horner's sign was recorded on the left eye in 8 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Modulation of ABH histo-blood group antigen expression in normal and myasthenic human thymus.

    PubMed

    Sarafian, Victoria S; Marinova, Tsvetana T

    2006-10-01

    The role of ABH histo-blood group antigens (HBGA) in intercellular communication during normal and pathological processes is still uncertain. The present work investigates the expression of ABH HBGA in epithelial cells and lymphocytes in normal thymus, and characterizes the modulation of their immunoreactivity during myasthenic transformation. Immunohistochemistry and immunoelectron microscopy were applied on normal young thymus and on myasthenia gravis-associated thymomas and thymic hyperplasias. The Hassall's corpuscules in the thymus of young individuals were homogeneously stained for HBGA, while in hyperplastic glands only their central part was positive. Stromal epithelial cells permanently expressed HBGA in all tissue samples. In thymomas, mainly the lymphocytes in close proximity to antigen expressing epithelial cells were positive, while in the hyperplastic gland the most intensely stained lymphocytes were those within Hassall's corpuscules. Novel evidence for modulation of ABH antigen reactivity in normal and myasthenic human thymus is presented. It suggests that HBGA might participate in the regulation of the cross-talk in the thymocyte microenvironment throughout the ontogeny, as well as during the myasthenic transformation.

  6. A new syndrome, congenital extraocular muscle fibrosis with ulnar hand anomalies, maps to chromosome 21qter

    PubMed Central

    Tukel, T; Uzumcu, A; Gezer, A; Kayserili, H; Yuksel-Apak, M; Uyguner, O; Gultekin, S; Hennies, H; Nurnberg, P; Desnick, R; Wollnik, B

    2005-01-01

    Objective: To describe a new autosomal recessive syndrome of CFEOM and ulnar hand abnormalities, and localise the disease causing gene. Methods: Clinical evaluation of the affected members and positional mapping. Results: Six affected patients with CFEOM/U (aged 2 to 29 years) from a large consanguineous Turkish family were studied. Ophthalmological involvement was characterised by non-progressive restrictive ophthalmoplegia with blepharoptosis of the right eye. The postaxial oligodactyly/oligosyndactyly of the hands was more severe on the right side. A genome-wide scan established linkage of this new autosomal recessive syndrome to a locus on chromosome 21qter. The multipoint LOD score was 4.53 at microsatellite marker D21S1259, and fine mapping defined a ∼1.5 Mb critical region between microsatellite marker D21S1897 and the telomere of the long arm. Conclusions: CFEOM/U maps to a 1.5 Mb region at chromosome 21qter. Future identification of the disease causing gene may provide insights into the development of the extraocular muscles and brain stem α motor neurones, as well as anteroposterior limb development. PMID:15863670

  7. Brown Syndrome

    MedlinePlus

    ... Does Brown syndrome cause eye problems besides abnormal eye movements? In the more severely affected cases of Brown ... acquired and congenital cases. In congenital cases, the eye movement problem is usually constant and unlikely to resolve ...

  8. Leber's congenital amaurosis.

    PubMed

    De Laey, J J

    1991-01-01

    Leber's congenital amaurosis is an autosomal recessive disorder, characterized by the onset of blindness before the age of 6 months, a variable fundus aspect and an absent or extremely pathological ERG. The disorder may be isolated or associated with systemic involvement, such as nephronophtisis (Senior-Loken syndrome), nephronophtisis, cone-shaped epiphyses of the hand and cerebellar ataxia (Saldino-Mainzer syndrome), vermis hypoplasia, oculomotor anomalies and respiratory problems in the neonatal period (Joubert syndrome) or cardiomyopathy. It should be differentiated from other forms or chorioretinal dystrophies (juvenile retinitis pigmentosa or congenital stationary night blindness), cortical blindness or maturation delay and metabolic disorders. Children with possible congenital Leber amaurosis should not only have a thorough ophthalmological examination, but should also be seen by a paediatrician experienced in metabolic disorders.

  9. Associations Between TGFA/TGFB3/MSX1 Gene Polymorphisms and Congenital Non-Syndromic Hearing Impairment in a Chinese Population

    PubMed Central

    Du, Jihong; Deng, Jianhua

    2016-01-01

    Background The aim of this study was to investigate whether the TGFA/TGFB3/MSX1 gene polymorphisms and haplotypes lead to individual differences between congenital non-syndromic hearing impairment (NSHI) patients and normal people in a Chinese population and to analyze the risk factors for NSHI. Material/Methods Between December 2010 and September 2014, 343 congenital NSHI patients were recruited as cases, and 272 healthy subjects were recruited as controls. Denaturing high-performance liquid chromatography (DHPLC) was used to identify genotypes, SHEsis software was used to conduct gene linkage disequilibrium and haplotype analyses, and regression analysis was performed to identify risk factors for congenital NSHI. Results The distribution of genotype frequencies and allele frequencies of TGFA rs3771494, TGFB3 rs3917201 and rs2268626, and MSX1 rs3821949 and rs62636562 were significantly different between the case and the control groups (all P<0.05). TGFA/TGFB3/MSX1 gene rs3771494, rs1058213, rs3917201, rs2268626, rs3821949, and rs62636562 haplotype analysis showed that haplotype CCGTAC and TTACGT might be protective factors (both P<0.001), while TTGCGC might be a risk factor for the normal population (P<0.001). The other risk factors include paternal smoking, advanced maternal age, maternal sickness history, maternal contact with pesticides or similar drugs, maternal abortion history, maternal medication history, maternal passive smoking history during pregnancy, rs3771494 CT, rs2268626 CC and TC, and rs3821949 GG and AG genotypes were risk factors (all P<0.05), while maternal vitamin supplements during pregnancy, rs3917201 GA, rs62636562 TT and CT genotypes were protective factors for congenital NSHI (all P<0.05). Conclusions rs3771494, rs3917201, rs2268626, rs3821949 and rs62636562 might be associated with congenital NSHI. PMID:27356075

  10. Congenital hypogonadotropic hypogonadism and Kallmann syndrome as models for studying hormonal regulation of human testicular endocrine functions.

    PubMed

    Trabado, Séverine; Lamothe, Sophie; Maione, Luigi; Bouvattier, Claire; Sarfati, Julie; Brailly-Tabard, Sylvie; Young, Jacques

    2014-05-01

    Men with Kallmann syndrome (KS) and those with congenital isolated hypogonadotropic hypogonadism with normal olfaction share a chronic, usually profound deficit, in FSH and LH, the two pituitary gonadotropins. Many studies indicate that this gonadotropin deficiency is already present during fetal life, thus explaining the micropenis, cryptorchidism and marked testicular hypotrophy already present at birth. In addition, neonatal activation of gonadotropin secretion is compromised in boys with severe CHH/Kallmann, preventing the first phase of postnatal testicular activation. Finally, CHH is characterized by the persistence, in the vast majority of cases, of gonadotropin deficiency at the time of puberty and during adulthood. This prevents the normal pubertal testicular reactivation required for physiological sex steroid and testicular peptide production, and for spermatogenesis. CHH/KS thus represents a pathological paradigm that can help to unravel, in vivo, the role of each gonadotropin in human testicular exocrine and endocrine functions at different stages of development. Recombinant gonadotropins with pure LH or FSH activity have been used to stimulate Leydig's cells and Sertoli's cells, respectively, and thereby to clarify their paracrine interaction in vivo. The effects of these pharmacological probes can be assessed by measuring the changes they provoke in circulating testicular hormone concentrations. This review discusses the impact of chronic gonadotropin deficiency on the endocrine functions of the interstitial compartment, which contains testosterone-, estradiol- and INSL3-secreting Leydig's cells. It also examines the regulation of inhibin B and anti-Mullerian hormone (AMH) secretion in the seminiferous tubules, and the insights provided by studies of human testicular stimulation with recombinant gonadotropins, used either individually or in combination.

  11. The Cerebral Cost of Breathing: An fMRI Case-Study in Congenital Central Hypoventilation Syndrome

    PubMed Central

    Sharman, Mike; Gallea, Cécile; Lehongre, Katia; Galanaud, Damien; Nicolas, Nathalie; Similowski, Thomas; Cohen, Laurent; Straus, Christian; Naccache, Lionel

    2014-01-01

    Certain motor activities - like walking or breathing - present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks - including various frontal lobe areas - subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the “resting state” pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active

  12. Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import*

    PubMed Central

    Di Lascio, Simona; Belperio, Debora

    2016-01-01

    Heterozygous mutations of the human PHOX2B gene, a key regulator of autonomic nervous system development, lead to congenital central hypoventilation syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing. Polyalanine expansions in the 20-residues region of the C terminus of PHOX2B are the major mutations responsible for CCHS. Elongation of the alanine stretch in PHOX2B leads to a protein with altered DNA binding, transcriptional activity, and nuclear localization and the possible formation of cytoplasmic aggregates; furthermore, the findings of various studies support the idea that CCHS is not due to a pure loss of function mechanism but also involves a dominant negative effect and/or toxic gain of function for PHOX2B mutations. Because PHOX2B forms homodimers and heterodimers with its paralogue PHOX2A in vitro, we tested the hypothesis that the dominant negative effects of the mutated proteins are due to non-functional interactions with the wild-type protein or PHOX2A using a co-immunoprecipitation assay and the mammalian two-hybrid system. Our findings show that PHOX2B forms homodimers and heterodimerizes weakly with mutated proteins, exclude the direct involvement of the polyalanine tract in dimer formation, and indicate that mutated proteins retain partial ability to form heterodimers with PHOX2A. Moreover, in this study, we investigated the effects of the longest polyalanine expansions on the homeodomain-mediated nuclear import, and our data clearly show that the expanded C terminus interferes with this process. These results provide novel insights into the effects of the alanine tract expansion on PHOX2B folding and activity. PMID:27129232

  13. PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome

    PubMed Central

    Zhao, Cui-Mei; Peng, Lu-Ying; Li, Li; Liu, Xing-Yuan; Wang, Juan; Zhang, Xian-Ling; Yuan, Fang; Li, Ruo-Gu; Qiu, Xing-Biao; Yang, Yi-Qing

    2015-01-01

    Congenital heart disease (CHD), the most common type of birth defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier’s family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with endocardial cushion defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS. PMID:25893250

  14. [Congenital knee dislocation: case report].

    PubMed

    Arvinius, C; Luque, R; Díaz-Ceacero, C; Marco, F

    2016-01-01

    Congenital knee dislocation is an infrequent condition with unknown etiology. In some cases it occurs as an isolated condition, while in others it coexists with associated conditions or syndromes. The treatment of congenital knee dislocation is driven by the severity and flexibility of the deformity. The literature includes from serial casting or the Pavlik harness to quadriceps tendon plasty or femoral osteotomies. We report herein the case of a congenital dislocation treated with serial casting with a good outcome.

  15. Autosomal and X Chromosome Structural Variants Are Associated with Congenital Heart Defects in Turner Syndrome: The NHLBI GenTAC Registry

    PubMed Central

    Prakash, Siddharth K.; Bondy, Carolyn A.; Maslen, Cheryl L.; Silberbach, Michael; Lin, Angela E.; Perrone, Laura; Limongelli, Giuseppe; Michelena, Hector I.; Bossone, Eduardo; Citro, Rodolfo; Lemaire, Scott A.; Body, Simon C.; Milewicz, Dianna M.

    2016-01-01

    Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14 and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. PMID:27604636

  16. Autosomal and X chromosome structural variants are associated with congenital heart defects in Turner syndrome: The NHLBI GenTAC registry.

    PubMed

    Prakash, Siddharth K; Bondy, Carolyn A; Maslen, Cheryl L; Silberbach, Michael; Lin, Angela E; Perrone, Laura; Limongelli, Giuseppe; Michelena, Hector I; Bossone, Eduardo; Citro, Rodolfo; Lemaire, Scott A; Body, Simon C; Milewicz, Dianna M

    2016-12-01

    Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc.

  17. Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

    NASA Astrophysics Data System (ADS)

    Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

    2004-05-01

    A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution—plotted as a current-arrow map (CAM)—calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter.

  18. Congenital subclavian steal syndrome with multiple cerebellar infarctions caused by an atypical circumflex retroesophageal right aortic arch with atretic aberrant left subclavian artery.

    PubMed

    Mamopoulos, Apostolos T; Luther, Bernd

    2014-09-01

    A right-sided aortic arch is a rare anomaly with an incidence of 0.1% worldwide and is usually associated with a mirror image of all supra-aortic branches or an aberrant left subclavian artery. The latter is often associated with a Kommerell diverticulum, although it can rarely be hypoplastic or atretic and lead to congenital subclavian steal. In most patients, the situation is well-tolerated. In this report, we present a case of subclavian steal syndrome with multiple cerebellar infarcts in a patient with an atypical right-sided aortic arch and an atretic aberrant left subclavian artery arising from a left-sided descending thoracic aorta.

  19. A de novo splice site mutation in CASK causes FG syndrome-4 and congenital nystagmus.

    PubMed

    Dunn, P; Prigatano, G P; Szelinger, S; Roth, J; Siniard, A L; Claasen, A M; Richholt, R F; De Both, M; Corneveaux, J J; Moskowitz, A M; Balak, C; Piras, I S; Russell, M; Courtright, A L; Belnap, N; Rangasamy, S; Ramsey, K; Opitz, J M; Craig, D W; Narayanan, V; Huentelman, M J; Schrauwen, I

    2017-03-01

    Mutations in CASK cause X-linked intellectual disability, microcephaly with pontine and cerebellar hypoplasia, optic atrophy, nystagmus, feeding difficulties, GI hypomotility, and seizures. Here we present a patient with a de novo carboxyl-terminus splice site mutation in CASK (c.2521-2A>G) and clinical features of the rare FG syndrome-4 (FGS4). We provide further characterization of genotype-phenotype correlations in CASK mutations and the presentation of nystagmus and the FGS4 phenotype. There is considerable variability in clinical phenotype among patients with a CASK mutation, even among variants predicted to have similar functionality. Our patient presented with developmental delay, nystagmus, and severe gastrointestinal and gastroesophageal complications. From a cognitive and neuropsychological perspective, language skills and IQ are within normal range, although visual-motor, motor development, behavior, and working memory were impaired. The c.2521-2A>G splice mutation leads to skipping of exon 26 and a 9 base-pair deletion associated with a cryptic splice site, leading to a 28-AA and a 3-AA in-frame deletion, respectively (p.Ala841_Lys843del and p.Ala841_Glu868del). The predominant mutant transcripts contain an aberrant guanylate kinase domain and thus are predicted to degrade CASK's ability to interact with important neuronal and ocular development proteins, including FRMD7. Upregulation of CASK as well as dysregulation among a number of interactors is also evident by RNA-seq. This is the second CASK mutation known to us as cause of FGS4. © 2017 Wiley Periodicals, Inc.

  20. Leber's congenital amaurosis as conceived by Leber.

    PubMed

    Pinckers, A J

    1979-01-01

    Not being satisfied with the present-day diagnosis of Leber's congenital amaurosis, the original papers written by Leber were studied. It gradually became clear that what Leber had in mind with congenital amaurosis is roughly the same as what we know as neuronal ceroid lipofuscinosis. The present diagnosis of Leber's congenital amaurosis is not a clinical syndrome but an aspecific symptom complex.

  1. Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

    PubMed Central

    Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

  2. The role of abnormalities in the distal pathway of cholesterol synthesis in the Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD) syndrome.

    PubMed

    Seeger, Mark A; Paller, Amy S

    2014-03-01

    CHILD syndrome (Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects) is a rare X-linked dominant ichthyotic disorder. CHILD syndrome results from loss of function mutations in the NSDHL gene, which leads to inhibition of cholesterol synthesis and accumulation of toxic metabolic intermediates in affected tissues. The CHILD syndrome skin is characterized by plaques topped by waxy scales and a variety of developmental defects in extracutaneous tissues, particularly limb hypoplasia or aplasia. Strikingly, these alterations are commonly segregated to either the right or left side of the body midline with little to no manifestations on the ipsilateral side. By understanding the underlying disease mechanism of CHILD syndrome, a pathogenesis-based therapy has been developed that successfully reverses the CHILD syndrome skin phenotype and has potential applications to the treatment of other ichthyoses. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

  3. Congenital Insensitivity to Pain with Anhidrosis (HSAN Type IV), Extremely Rare Syndrome that Can Be Easily Missed by Bone and Joint Surgeons: A Case Report

    PubMed Central

    Ali, Nadeem; Sharma, Sudesh; Sharma, Sonali; Kamal, Younis; Sharma, Sushil

    2012-01-01

    Background Congenital insensitivity to pain with anhidrosis is an extremely rare disorder in which injuries can often be missed by patient, parents and even by orthopedic surgeon. Pain and tenderness, on which a trauma team so much depends to make a clinical diagnosis and to decide whether to go for radiological evaluation can be misleading in this rare syndrome. So complete clinical examination still forms the corner stone to avoid misdiagnosis and pick up the rare disorders. Case Presentation We present a 5 year old girl child, who was brought to us as a case of one and a half month old neglected trauma left leg and was diagnosed to be suffering from congenital insensitivity to pain with anhidrosis (HSAN Type IV). Conclusion Congenital insensitivity to pain with anhidrosis is extremely rare entity, in which patients are subjected to repeated injuries which are often neglected. There is no specific treatment but patient training and parent education are key to avoid further neglect and damage. PMID:23429452

  4. Possible rare congenital dysinnervation disorder: congenital ptosis associated with adduction.

    PubMed

    Mendes, Sílvia; Beselga, Diana; Campos, Sónia; Neves, Arminda; Campos, Joana; Carvalho, Sílvia; Silva, Eduardo; Castro Sousa, João Paulo

    2015-01-01

    Ptosis is defined as an abnormally low position of the upper eyelid margin. It can be congenital or acquired, uni or bilateral, and isolated or associated with other ocular and nonocular defects. We report a case of a female child, aged 8 years, with congenital right ptosis increased on right adduction and with left ptosis on left adduction. There was no horizontal ocular movement limitation. Apparent underaction of the right inferior oblique muscle was also present. We believe that within the possible mechanisms it is more likely that it is a congenital innervation dysgenesis syndrome (CID)/congenital cranial dysinnervation disorder (CCDD).

  5. Genetics Home Reference: critical congenital heart disease

    MedlinePlus

    ... right ventricle, D-transposition of the great arteries , Ebstein anomaly, hypoplastic left heart syndrome , interrupted aortic arch, ... Testing Registry: Congenital heart disease Genetic Testing Registry: Ebstein's anomaly Genetic Testing Registry: Hypoplastic left heart syndrome ...

  6. A Rare Case of Acroangiodermatitis Associated with a Congenital Arteriovenous Malformation (Stewart-Bluefarb Syndrome) in a Young Veteran: Case Report and Review of the Literature.

    PubMed

    Archie, Mark; Khademi, Saieh; Aungst, David; Nouvong, Aksone; Freeman, Shanna; Gelabert, Hugh; Rigberg, David; deVirgilio, Christian; Lewis, Michael; O'Connell, Jessica

    2015-10-01

    Acroangiodermatitis (AD) is a rare angioproliferative disease manifesting with cutaneous lesions clinically similar to Kaposi's sarcoma. AD is a benign hyperplasia of preexisting vasculature and may be associated with acquired or congenital arteriovenous malformations (AVM), or severe chronic venous insufficiency (because of hypostasis, elevated venous pressure, arteriovenous shunting). Stewart-Bluefarb syndrome is the rare syndrome in which AD is associated with a congenital AVM. We present the case of a young veteran with a painful, chronic nonhealing ulcer and ipsilateral popliteal artery occlusion likely because of trauma, who elected transmetatarsal amputation for symptomatic relief. A 24-year-old male veteran presented with a 5-year history of a nonhealing dorsal left foot ulcer, resulting from a training exercise injury. He ultimately developed osteomyelitis requiring antibiotics, frequent debridements, multiple trials of unsuccessful skin substitute grafting, and severe unremitting pain. He noted a remote history of left digital deformities treated surgically as a child, and an AVM, previously endovascularly treated at an outside facility. Arterial duplex revealed somewhat dampened left popliteal, posterior tibial (PT), and dorsalis pedis (DP) artery signals with arterial brachial index of 1.0. CT angiography showed occlusion of the proximal to mid popliteal artery with significant calcifications felt initially to be a result of prior trauma. Pedal pulses were palpable and transcutaneous oxygen measurements revealed adequate oxygenation. Because of unremitting pain, the patient opted for amputation. Pathology revealed vascular proliferation consistent with AD. This case illustrates an unusual diagnosis of acroangiodermatitis, and a rare syndrome when associated with his underlying AVM (Stewart-Bluefarb syndrome). This resulted in a painful, chronic ulcer and was further complicated by trauma-related arterial occlusive disease. AD disease can hinder wound

  7. De Novo Mutations in NALCN Cause a Syndrome Characterized by Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay

    PubMed Central

    Chong, Jessica X.; McMillin, Margaret J.; Shively, Kathryn M.; Beck, Anita E.; Marvin, Colby T.; Armenteros, Jose R.; Buckingham, Kati J.; Nkinsi, Naomi T.; Boyle, Evan A.; Berry, Margaret N.; Bocian, Maureen; Foulds, Nicola; Uzielli, Maria Luisa Giovannucci; Haldeman-Englert, Chad; Hennekam, Raoul C.M.; Kaplan, Paige; Kline, Antonie D.; Mercer, Catherine L.; Nowaczyk, Malgorzata J.M.; Klein Wassink-Ruiter, Jolien S.; McPherson, Elizabeth W.; Moreno, Regina A.; Scheuerle, Angela E.; Shashi, Vandana; Stevens, Cathy A.; Carey, John C.; Monteil, Arnaud; Lory, Philippe; Tabor, Holly K.; Smith, Joshua D.; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.; Shendure, Jay; Nickerson, Deborah A.; Abecasis, Gonçalo R.; Anderson, Peter; Blue, Elizabeth Marchani; Annable, Marcus; Browning, Brian L.; Buckingham, Kati J.; Chen, Christina; Chin, Jennifer; Chong, Jessica X.; Cooper, Gregory M.; Davis, Colleen P.; Frazar, Christopher; Harrell, Tanya M.; He, Zongxiao; Jain, Preti; Jarvik, Gail P.; Jimenez, Guillaume; Johanson, Eric; Jun, Goo; Kircher, Martin; Kolar, Tom; Krauter, Stephanie A.; Krumm, Niklas; Leal, Suzanne M.; Luksic, Daniel; Marvin, Colby T.; McMillin, Margaret J.; McGee, Sean; O’Reilly, Patrick; Paeper, Bryan; Patterson, Karynne; Perez, Marcos; Phillips, Sam W.; Pijoan, Jessica; Poel, Christa; Reinier, Frederic; Robertson, Peggy D.; Santos-Cortez, Regie; Shaffer, Tristan; Shephard, Cindy; Shively, Kathryn M.; Siegel, Deborah L.; Smith, Joshua D.; Staples, Jeffrey C.; Tabor, Holly K.; Tackett, Monica; Underwood, Jason G.; Wegener, Marc; Wang, Gao; Wheeler, Marsha M.; Yi, Qian; Bamshad, Michael J.

    2015-01-01

    Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with “DA2A with severe neurological abnormalities” and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with “atypical” forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s). PMID:25683120

  8. Congenital Diaphragmatic Hernia and Microtia in a Newborn with Mycophenolate Mofetil (MMF) Exposure: Phenocopy for Fryns Syndrome or Broad Spectrum of Teratogenic Effects?

    PubMed Central

    Parisi, Melissa A.; Zayed, Hatem; Slavotinek, Anne M.; Rutledge, Joe C.

    2009-01-01

    A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day two of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data. PMID:19449404

  9. Congenital diaphragmatic hernia and microtia in a newborn with mycophenolate mofetil (MMF) exposure: phenocopy for Fryns syndrome or broad spectrum of teratogenic effects?

    PubMed

    Parisi, Melissa A; Zayed, Hatem; Slavotinek, Anne M; Rutledge, Joe C

    2009-06-01

    A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day 2 of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data.

  10. X-linked congenital hypertrichosis syndrome is associated with interchromosomal insertions mediated by a human-specific palindrome near SOX3.

    PubMed

    Zhu, Hongwen; Shang, Dandan; Sun, Miao; Choi, Sunju; Liu, Qing; Hao, Jiajie; Figuera, Luis E; Zhang, Feng; Choy, Kwong Wai; Ao, Yang; Liu, Yang; Zhang, Xiao-Lin; Yue, Fengzhen; Wang, Ming-Rong; Jin, Li; Patel, Pragna I; Jing, Tao; Zhang, Xue

    2011-06-10

    X-linked congenital generalized hypertrichosis (CGH), an extremely rare condition characterized by universal overgrowth of terminal hair, was first mapped to chromosome Xq24-q27.1 in a Mexican family. However, the underlying genetic defect remains unknown. We ascertained a large Chinese family with an X-linked congenital hypertrichosis syndrome combining CGH, scoliosis, and spina bifida and mapped the disease locus to a 5.6 Mb critical region within the interval defined by the previously reported Mexican family. Through the combination of a high-resolution copy-number variation (CNV) scan and targeted genomic sequencing, we identified an interchromosomal insertion at Xq27.1 of a 125,577 bp intragenic fragment of COL23A1 on 5q35.3, with one X breakpoint within and the other very close to a human-specific short palindromic sequence located 82 kb downstream of SOX3. In the Mexican family, we found an interchromosomal insertion at the same Xq27.1 site of a 300,036 bp genomic fragment on 4q31.2, encompassing PRMT10 and TMEM184C and involving parts of ARHGAP10 and EDNRA. Notably, both of the two X breakpoints were within the short palindrome. The two palindrome-mediated insertions fully segregate with the CGH phenotype in each of the families, and the CNV gains of the respective autosomal genomic segments are not present in the public database and were not found in 1274 control individuals. Analysis of control individuals revealed deletions ranging from 173 bp to 9104 bp at the site of the insertions with no phenotypic consequence. Taken together, our results strongly support the pathogenicity of the identified insertions and establish X-linked congenital hypertrichosis syndrome as a genomic disorder.

  11. Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

    ClinicalTrials.gov

    2016-09-01

    Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

  12. Congenital Hypothyroidism

    MedlinePlus

    ... Disease Featured Resource Find an Endocrinologist Search Congenital Hypothyroidism March 2012 Download PDFs English Espanol Editors Rosalind S. ... Pediatric Endocrine Society MedlinePlus (NIH) What is congenital hypothyroidism? Newborn babies who are unable to make enough ...

  13. Anomalous origin of the right pulmonary artery from the ascending aorta accompanied by absent pulmonary valve syndrome and right-sided aortic arch: a rare case in adult congenital heart disease.

    PubMed

    Khajali, Zahra; Mohammadzadeh, Ali; Khayatzadeh, Marzieh

    2015-04-01

    We present a rare congenital heart disease in a 20-year-old man with anomalous origin of the right pulmonary artery from the ascending aorta, accompanied by absent pulmonary valve syndrome, and a right-sided aortic arch suspected initially in transthoracic echocardiography and subsequently confirmed by cardiac catheterisation and computed tomography angiography.

  14. Congenital Neutropenia Syndromes

    MedlinePlus

    ... Prepare Your Application Draft Specific Aims Outline Your Experiments Know Your Audience Write Your Research Plan Plan ... PHS Assignment Request Form Research with Special Considerations Human Subjects Decision Trees Inclusion of Women Part 1 ...

  15. A Case of Epidermal Nervous Syndrome with a Novel Association of Congenital Cystic Dysplastic Kidney with Numerous Nephroblastic Proliferations

    DTIC Science & Technology

    2016-04-19

    syndrome. We present a unique case of a female neonate with a medical history significant for seizure-like activity, a hyperplastic thryoid nodelue. aortic coarctaction, patent ductus arterlosus, and epidermal nevus syndrome.

  16. Genetics Home Reference: ALG6-congenital disorder of glycosylation

    MedlinePlus

    ... also known as congenital disorder of glycosylation type Ic) is an inherited condition that affects many parts ... Condition ALG6-CDG carbohydrate-deficient glycoprotein syndrome type Ic carbohydrate-deficient glycoprotein syndrome type V CDG syndrome ...

  17. Apert Syndrome.

    PubMed

    Datta, Saikat; Saha, Sandip; Kar, Arnab; Mondal, Souvonik; Basu, Syamantak

    2014-09-01

    Apert syndrome is one of the craniosynostosis syndromes which, due to its association with other skeletal anomalies, is also known as acrocephalosyndactyly. It is a rare congenital anomaly which stands out from other craniosynostosis due to its characteristic skeletal presentations.

  18. Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome

    PubMed Central

    Herrmann, David N.; Bansagi, Boglarka; Hasan, Bashar Awwad Shiekh; Lofra, Robert Muni; Logigian, Eric L.; Sowden, Janet E.; Almodovar, Jorge L.; Littleton, J. Troy; Zuchner, Stephan; Horvath, Rita; Lochmüller, Hanns

    2015-01-01

    Objectives: To describe the clinical and electrophysiologic features of synaptotagmin II (SYT2) mutations, a novel neuromuscular syndrome characterized by foot deformities and fatigable ocular and lower limb weakness, and the response to modulators of acetylcholine release. Methods: We performed detailed clinical and neurophysiologic assessment in 2 multigenerational families with dominant SYT2 mutations (c.920T>G [p.Asp307Ala] and c.923G>A [p.Pro308Leu]). Serial clinical and electrophysiologic assessments were performed in members of one family treated first with pyridostigmine and then with 3,4-diaminopyridine. Results: Electrophysiologic testing revealed features indicative of a presynaptic deficit in neurotransmitter release with posttetanic potentiation lasting up to 60 minutes. Treatment with 3,4-diaminopyridine produced both a clinical benefit and an improvement in neuromuscular transmission. Conclusion: SYT2 mutations cause a novel and potentially treatable complex presynaptic congenital myasthenic syndrome characterized by motor neuropathy causing lower limb wasting and foot deformities, with reflex potentiation following exercise and a uniquely prolonged period of posttetanic potentiation. PMID:26519543

  19. A Deletion in FOXN1 Is Associated with a Syndrome Characterized by Congenital Hypotrichosis and Short Life Expectancy in Birman Cats

    PubMed Central

    Abitbol, Marie; Bossé, Philippe; Thomas, Anne; Tiret, Laurent

    2015-01-01

    An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a FOXN1 (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in FOXN1 have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in FOXN1 in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated FOXN1 protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between FOXN1 and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines. PMID:25781316

  20. Mutations in SMG9, Encoding an Essential Component of Nonsense-Mediated Decay Machinery, Cause a Multiple Congenital Anomaly Syndrome in Humans and Mice

    PubMed Central

    Shaheen, Ranad; Anazi, Shams; Ben-Omran, Tawfeg; Seidahmed, Mohammed Zain; Caddle, L. Brianna; Palmer, Kristina; Ali, Rehab; Alshidi, Tarfa; Hagos, Samya; Goodwin, Leslie; Hashem, Mais; Wakil, Salma M.; Abouelhoda, Mohamed; Colak, Dilek; Murray, Stephen A.; Alkuraya, Fowzan S.

    2016-01-01

    Nonsense-mediated decay (NMD) is an important process that is best known for degrading transcripts that contain premature stop codons (PTCs) to mitigate their potentially harmful consequences, although its regulatory role encompasses other classes of transcripts as well. Despite the critical role of NMD at the cellular level, our knowledge about the consequences of deficiency of its components at the organismal level is largely limited to model organisms. In this study, we report two consanguineous families in which a similar pattern of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutations in SMG9, encoding an essential component of the SURF complex that generates phospho-UPF1, the single most important step in NMD. By knocking out Smg9 in mice via CRISPR/Cas9, we were able to recapitulate the major features of the SMG9-related multiple congenital anomaly syndrome we observed in humans. Surprisingly, human cells devoid of SMG9 do not appear to have reduction of PTC-containing transcripts but do display global transcriptional dysregulation. We conclude that SMG9 is required for normal human and murine development, most likely through a transcriptional regulatory role, the precise nature of which remains to be determined. PMID:27018474

  1. Early onset bilateral juvenile myasthenia gravis masquerading as simple congenital ptosis.

    PubMed

    Alam, Md Shahid; Devi Nivean, Pratheeba

    2017-01-01

    Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction. Ocular myasthenia gravis presents as ptosis with extraocular motility restriction and is prone to be misdiagnosed as third nerve palsy or congenital or aponeurotic ptosis. Juvenile ocular myasthenia gravis in very young children is difficult to diagnose and can be easily labeled as a case of congenital ptosis, the more so when the condition is bilateral. We present a case of a two-year-old child who presented with bilateral ptosis and was diagnosed as a case of simple congenital ptosis elsewhere with the advice to undergo tarsofrontalis sling surgery. The child was diagnosed with juvenile myasthenia gravis on thorough history, examination, and systemic evaluation and was started on anti-myasthenic treatment.

  2. Early onset bilateral juvenile myasthenia gravis masquerading as simple congenital ptosis

    PubMed Central

    Alam, Md. Shahid; Devi Nivean, Pratheeba

    2017-01-01

    Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction. Ocular myasthenia gravis presents as ptosis with extraocular motility restriction and is prone to be misdiagnosed as third nerve palsy or congenital or aponeurotic ptosis. Juvenile ocular myasthenia gravis in very young children is difficult to diagnose and can be easily labeled as a case of congenital ptosis, the more so when the condition is bilateral. We present a case of a two-year-old child who presented with bilateral ptosis and was diagnosed as a case of simple congenital ptosis elsewhere with the advice to undergo tarsofrontalis sling surgery. The child was diagnosed with juvenile myasthenia gravis on thorough history, examination, and systemic evaluation and was started on anti-myasthenic treatment. PMID:28293536

  3. Congenital hemangiomas.

    PubMed

    Boull, Christina; Maguiness, Sheilagh M

    2016-09-01

    Congenital hemangiomas are rare solitary vascular tumors that do not proliferate after birth. They are characterized as either rapidly involuting congenital hemangiomas (RICHs) or noninvoluting congenital hemangiomas (NICHs) based on their clinical progression. NICHs have no associated complications, but are persistent. RICH, while usually asymptomatic, may ulcerate or bleed early in their presentation, but involute quickly during the first few months of life. Hepatic RICHs are not associated with cutaneous RICHs, but may result in high-output cardiac failure due to arteriovenous or portovenous shunting. In the following review, the clinical characteristics and current management specific to congenital hemangiomas is discussed.

  4. BDNF and its receptors in human myasthenic thymus: implications for cell fate in thymic pathology.

    PubMed

    Berzi, Angela; Ayata, C Korcan; Cavalcante, Paola; Falcone, Chiara; Candiago, Elisabetta; Motta, Teresio; Bernasconi, Pia; Hohlfeld, Reinhard; Mantegazza, Renato; Meinl, Edgar; Farina, Cinthia

    2008-07-15

    Here we show that in myasthenic thymus several cell types, including thymic epithelial cells (TEC) and immune cells, were the source and the target of the neurotrophic factor brain-derived growth factor (BDNF). Interestingly, many actively proliferating medullary thymocytes expressed the receptor TrkB in vivo in involuted thymus, while this population was lost in hyperplastic or neoplastic thymuses. Furthermore, in hyperplastic thymuses the robust coordinated expression of BDNF in the germinal centers together with the receptor p75NTR on all proliferating B cells strongly suggests that this factor regulates germinal center reaction. Finally, all TEC dying of apoptosis expressed BDNF receptors, indicating that this neurotrophin is involved in TEC turnover. In thymomas both BDNF production and receptor expression in TEC were strongly hindered. This may represent an attempt of tumour escape from cell death.

  5. A 1.1Mb deletion in distal 13q deletion syndrome region with congenital heart defect and postaxial polydactyly: additional support for a CHD locus at distal 13q34 region.

    PubMed

    Yang, Yi-Feng; Ai, Qi; Huang, Can; Chen, Jin-Lan; Wang, Jian; Xie, Li; Zhang, Wei-Zhi; Yang, Jin-Fu; Tan, Zhi-Ping

    2013-10-01

    13q deletion syndrome is a rare genetic disorder, especially for group 3 deletion (13q33-q34 deletion). Previously we described a patient with congenital heart defect and mental retardation and proposed that a distal 6Mb region might contain the causative gene of congenital heart defect. Here we present a new patient with congenital heart defects (CHD), hand and foot anomalies and mild mental retardation. We identified a 1.1Mb deletion at chromosome 13q34 with high resolution SNP-array BeadChips (HumanOmni1-Quad, Illumina, USA). This chromosome region contains ten annotated genes, including GRK1, TFDP1, RASA3 and GAS6. To our knowledge, this represents the smallest 13q34 deletion identified to date. Our study provides additional support that distal 13q34 deletion region might contain key gene(s) responsible for cardiac development.

  6. Down-Klinefelter syndrome (48,XXY,+21) in a child with congenital heart disease: case report and literature review.

    PubMed

    Shen, Zheng; Zou, Chao Chun; Shang, Shi Qiang; Jiang, Ke Wen

    2012-01-01

    Congenital heart disease (CHD) is extremely rarely reported in 48, XYY, +21 karyotype. Herein, we reported one case of 48,XYY,+21 karyotype with CHD and reviewed the available literature. The phenotypic characteristics of the 4-month-old child showed the presence of features typical of mongoloid slant. X-ray detection showed the form of heart was corpulent and the bilateral mediastinum was broad. Doppler echocardiogram detection showed atrial septal and ventricular septal defects with patent ductus arteriosus, pulmonary hypertension and mild tricuspid regurgitation. Including this case, 63 cases of 48, XYY, +21 chromosome pattern have been reported. However, only 9 cases have CHD.

  7. [Genetics of congenital deafness].

    PubMed

    Faundes, Víctor; Pardo, Rosa Andrea; Castillo Taucher, Silvia

    2012-10-20

    Congenital deafness is defined as the hearing loss which is present at birth and, consequently, before speech development. It is the most prevalent sensor neural disorder in developed countries, and its incidence is estimated between 1-3 children per 1,000 newborns, of which more than 50% are attributable to genetics causes. Deafness can be classified as syndromic or non-syndromic. In the first case, it is associated with outer ear malformations and/or systemic findings. More than 400 syndromes accompanied of deafness have been described, which represent about 30% of cases of congenital hearing loss. The remaining percentage corresponds to non-syndromic cases: 75-85% are autosomal recessive, 15-24% are autosomal dominant, and 1-2% are X-linked. The evaluation of a child with deafness requires a multidisciplinary collaboration among specialists, who must coordinate themselves and give information to the affected family. The aims of establishing a diagnosis are to predict other manifestations that may suggest some syndrome and to anticipate their management, as well as to perform genetic counseling to parents and affected individuals.

  8. Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome

    PubMed Central

    Mlynarski, Elisabeth E.; Sheridan, Molly B.; Xie, Michael; Guo, Tingwei; Racedo, Silvia E.; McDonald-McGinn, Donna M.; Gai, Xiaowu; Chow, Eva W.C.; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J.; Roberts, Amy E.; Piotrowicz, Małgorzata; Bearden, Carrie E.; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R.; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Shaikh, Tamim H.; Bassett, Anne S.; Goldmuntz, Elizabeth; Morrow, Bernice E.; Emanuel, Beverly S.

    2015-01-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n = 562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12 × 10−3, two-tailed Fisher’s exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30 × 10−2, two-tailed Fisher’s exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68 × 10−4, two-tailed Fisher’s exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS. PMID:25892112

  9. [Congenital retinal folds in different clinical cases].

    PubMed

    Munteanu, M

    2005-01-01

    We present 12 clinical cases of congenital retinal folds with different etiologies: posterior primitive vitreous persistency and hyperplasia (7 cases),retinocytoma (1 case). retinopathy of prematurity (1 case), astrocytoma of the retina (1 case), retinal vasculitis (1 case), Goldmann-Favre syndrome (1 case). Etiopathogenic and nosological aspects are discussed; the congenital retinal folds are interpreted as a symptom in a context of a congenital or acquired vitreo-retinal pathology.

  10. Metachronous Bilateral Testicular Leydig-Like Tumors Leading to the Diagnosis of Congenital Adrenal Hyperplasia (Adrenogenital Syndrome)

    PubMed Central

    Vukina, Josip; Chism, David D.; Sharpless, Julie L.; Raynor, Mathew C.; Milowsky, Matthew I.; Funkhouser, William K.

    2015-01-01

    A 33-year-old male with a history of left testis Leydig cell tumor (LCT), 3-month status after left radical orchiectomy, presented with a rapidly enlarging (0.6 cm to 3.7 cm) right testicular mass. He underwent a right radical orchiectomy, sections interpreted as showing a similar Leydig cell-like oncocytic proliferation, with a differential diagnosis including metachronous bilateral LCT and metachronous bilateral testicular tumors associated with congenital adrenal hyperplasia (a.k.a. “testicular adrenal rest tumors” (TARTs) and “testicular tumors of the adrenogenital syndrome” (TTAGS)). Additional workup demonstrated a markedly elevated serum adrenocorticotropic hormone (ACTH) and elevated adrenal precursor steroid levels. He was diagnosed with congenital adrenal hyperplasia, 3β-hydroxysteroid dehydrogenase deficiency (3BHSD) type, and started on treatment. Metachronous bilateral testicular masses in adults should prompt consideration of adult presentation of CAH. Since all untreated CAH patients are expected to have elevated serum ACTH, formal exclusion of CAH prior to surgical resection of a testicular Leydig-like proliferation could be accomplished by screening for elevated serum ACTH. PMID:26351608

  11. Preoperative Anxiety in Patients With Myasthenia Gravis and Risk for Myasthenic Crisis After Extended Transsternal Thymectomy: A CONSORT Study.

    PubMed

    Zou, Jianyong; Su, Chunhua; Lun, Xueping; Liu, Weibing; Yang, Weiling; Zhong, Beilong; Zhu, Haoshuai; Lei, Yiyan; Luo, Honghe; Chen, Zhenguang

    2016-03-01

    A thymectomy can ameliorate the symptoms of myasthenia gravis (MG) and prevent the progression of ocular MG (OMG) to generalized MG (GMG). However, postoperative myasthenic crisis (POMC) is a serious post-thymectomy complication. Preoperative anxiety (POA) is common but typically neglected in MG patients. The association of POA with POMC has not yet been examined.From June 2007 to December 2013, 541 cases of MG were admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). All cases underwent extended transsternal thymectomy (ETT). The clinical and pathological characteristics of these patients, including POA and POMC, were analyzed.A total of 179 patients experienced POA and 67 patients experienced POMC. Patients with POA were more likely to have POMC, a thymoma, and an ectopic thymus. Univariate analysis showed that POMC correlated with POA, presence of an ectopic thymus, dose of pyridostigmine bromide (PYR), presence of a thymoma, MGFA stage, preoperative myasthenic crisis, and postoperative pneumonia. Multivariate logistic regression analysis showed that the independent risk factors for POMC were POA, preoperative myasthenic crisis, higher dose of PYR, and postoperative pneumonia.Our results suggest that clinicians should consider the risk factors for POMC-especially preoperative anxiety-before performing a thymectomy in patients with MG.

  12. Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies

    ClinicalTrials.gov

    2017-02-16

    Congenital Fibrosis of Extraocular Muscles; Duane Retraction Syndrome; Duane Radial Ray Syndrome; Mobius Syndrome; Brown Syndrome; Marcus Gunn Syndrome; Strabismus Congenital; Horizontal Gaze Palsy; Horizontal Gaze Palsy With Progressive Scoliosis; Facial Palsy; Facial Paresis, Hereditary, Congenital; Third Nerve Palsy; Fourth Nerve Palsy; Sixth Nerve Palsy; Synkinesis; Ocular Motility Disorders; Levator-Medial Rectus Synkinesis; Athabaskan Brainstem Dysgenesis; Tongue Paralysis; Ninth Nerve Disorder; Fifth Nerve Palsy; Seventh Nerve Palsy; Eleventh Nerve Disorder; Twelfth Nerve Disorder; Vagus Nerve Paralysis; Moebius Sequence

  13. Congenital defects of C1 arches and odontoid process in a child with Down's syndrome: A case presentation

    PubMed Central

    Hatzantonis, Catherine; Muquit, Samiul; Nasto, Luigi Aurelio; Mehdian, Hossein

    2016-01-01

    We present the case of a 2-year-old child with Down's syndrome who presented to our unit with torticollis. Imaging studies revealed the rare occurrence of anterior and posterior C1 arch defects, absent odontoid process, and atlantoaxial subluxation. We managed her conservatively for 3 years without neurological deficits or worsening of atlantoaxial subluxation. We discuss the rare occurrences of anterior and posterior arch defects of the atlas, the radiological presentations of axis defects in patients, and the occurrence of atlantoaxial instability in patients with Down's syndrome. Management options with consideration to surgery in asymptomatic and symptomatic patients are also discussed. PMID:27217660

  14. Genetics Home Reference: congenital hepatic fibrosis

    MedlinePlus

    ... health and development? More about Mutations and Health Inheritance Pattern The various syndromes that include congenital hepatic fibrosis can have different inheritance patterns. Most of these disorders are inherited in an ...

  15. Ultra High-Resolution Gene Centric Genomic Structural Analysis of a Non-Syndromic Congenital Heart Defect, Tetralogy of Fallot

    PubMed Central

    Bittel, Douglas C.; Zhou, Xin-Gang; Kibiryeva, Nataliya; Fiedler, Stephanie; O’Brien, James E.; Marshall, Jennifer; Yu, Shihui; Liu, Hong-Yu

    2014-01-01

    Tetralogy of Fallot (TOF) is one of the most common severe congenital heart malformations. Great progress has been made in identifying key genes that regulate heart development, yet approximately 70% of TOF cases are sporadic and nonsyndromic with no known genetic cause. We created an ultra high-resolution gene centric comparative genomic hybridization (gcCGH) microarray based on 591 genes with a validated association with cardiovascular development or function. We used our gcCGH array to analyze the genomic structure of 34 infants with sporadic TOF without a deletion on chromosome 22q11.2 (n male = 20; n female = 14; age range of 2 to 10 months). Using our custom-made gcCGH microarray platform, we identified a total of 613 copy number variations (CNVs) ranging in size from 78 base pairs to 19.5 Mb. We identified 16 subjects with 33 CNVs that contained 13 different genes which are known to be directly associated with heart development. Additionally, there were 79 genes from the broader list of genes that were partially or completely contained in a CNV. All 34 individuals examined had at least one CNV involving these 79 genes. Furthermore, we had available whole genome exon arrays from right ventricular tissue in 13 of our subjects. We analyzed these for correlations between copy number and gene expression level. Surprisingly, we could detect only one clear association between CNVs and expression (GSTT1) for any of the 591 focal genes on the gcCGH array. The expression levels of GSTT1 were correlated with copy number in all cases examined (r = 0.95, p = 0.001). We identified a large number of small CNVs in genes with varying associations with heart development. Our results illustrate the complexity of human genome structural variation and underscore the need for multifactorial assessment of potential genetic/genomic factors that contribute to congenital heart defects. PMID:24498113

  16. Short stature with congenital ichthyosis.

    PubMed

    Lakhani, Som J; Lakhani, Om J

    2015-12-09

    PIBIDS syndrome (photosensitivity, ichthyosis, brittle hair, intellectual impairment, decreased fertility and short stature) is a variant of trichothiodystrophy. It is a rare form of autosomal recessive congenital ichthyosis. Short stature is a vital component of PIBIDS syndrome. We present the cases of two siblings in whom we diagnosed PIBIDS syndrome. On evaluation for short stature, they were found to have severe vitamin D deficiency, which on correction led to the patients having considerable gain in stature. With this case, we would also like to propose that vitamin D deficiency could be one of the treatable causes of short stature in PIBIDS syndrome.

  17. [Congenital thrombophilia].

    PubMed

    Kojima, Tetsuhito

    2016-03-01

    Congenital thrombophilia is a thrombotic diathesis caused by a variety of genetic abnormalities in blood coagulation factors or their inhibitory factors associated with physiological thrombus formation. Patients with congenital thrombophilia often present with unusual clinical episodes of venous thrombosis (occasionally combined with pulmonary embolism, known as venous thromboembolism) at a young age and recurrence in atypical vessels, such as the mesenteric vein and superior sagittal sinus, often with a family history of this condition. Studies in Japan as well as in western countries have shown congenital thrombophilia to be caused by a wide variety of genetic abnormalities in natural anticoagulant proteins, such as antithrombin, protein C, and protein S. However, there may still be many unknown causes of hereditary thrombosis. We recently reported a case of hereditary thrombosis induced by a novel mechanism of antithrombin resistance, that is, congenital thrombophilia caused by a gain-of-function mutation in the gene encoding the coagulation factor prothrombin.

  18. Congenital cataract

    MedlinePlus

    ... Congenital and inherited cataracts. In: Tasman W, Jaeger EA, eds. Duane's Ophthalmology . 16th ed. Philadelphia, PA: Lippincott ... Cataracts and systemic disease. In: Tasman W, Jaeger EA, eds. Duane's Ophthalmology . 16th ed. Philadelphia, PA: Lippincott ...

  19. Congenital Myopathy

    MedlinePlus

    ... arms and legs, droopy eyelids, and problems with eye movements. Weakness often gets worse with time. Central core ... difficulties occur as well. Some children have weakened eye movements. Congenital fiber-type disproportion myopathy is a rare ...

  20. Congenital rubella

    MedlinePlus

    ... is infected with the virus that causes German measles. Congenital means the condition is present at birth. ... Gershon AA. Rubella virus (German measles). In: Mandell GL, Bennett JE, ... . 8th ed. Philadelphia, PA: Elsevier Churchill Livingstone; ...

  1. Congenital syphilis

    MedlinePlus

    Congenital lues; Fetal syphilis ... which is passed from mother to child during fetal development or at birth. Nearly half of all ... Saunders; 2014:chap 143. Duff P. Maternal and fetal infections. In: Creasy RK, Resnik R, Iams JD, ...

  2. Assignment of the disease locus for lethal congenital contracture syndrome to a restricted region of chromosome 9q34, by genome scan using five affected individuals.

    PubMed

    Mäkelä-Bengs, P; Järvinen, N; Vuopala, K; Suomalainen, A; Ignatius, J; Sipilä, M; Herva, R; Palotie, A; Peltonen, L

    1998-08-01

    Lethal congenital contracture syndrome (LCCS) is an autosomal recessive disease leading to death before the 32d gestational week. It is characterized by the fetal akinesia phenotype, with highly focused degeneration of motoneurons in the spinal cord as the main neuropathological finding. We report here the assignment of the LCCS locus to a defined region of chromosome 9q34, between markers D9S1825 and D9S1830. The initial genome scan was performed with the DNA samples of only five affected individuals from two unrelated LCCS families. The conventional linkage analysis performed with 20 affected individuals and their families was focused on those chromosomal regions in which the affected siblings were identical by descent in the initial scan. One core haplotype of 3 cM was observed in LCCS alleles, supporting the assumption of one major mutation underlying LCCS, and linkage disequilibrium analysis restricted the critical chromosomal region to <100 kb in the vicinity of marker D9S61. Two genes, NGAL (neutrophil gelatinase-associated lipocalin and NOTCH 1, were excluded as causative genes for LCCS

  3. Immunity to polio, measles and rubella in women of child-bearing age and estimated congenital rubella syndrome incidence, Cambodia, 2012.

    PubMed

    Mao, B; Chheng, K; Wannemuehler, K; Vynnycky, E; Buth, S; Soeung, S C; Reef, S; Weldon, W; Quick, L; Gregory, C J

    2015-07-01

    Significant gaps in immunity to polio, measles, and rubella may exist in adults in Cambodia and threaten vaccine-preventable disease (VPD) elimination and control goals, despite high childhood vaccination coverage. We conducted a nationwide serological survey during November-December 2012 of 2154 women aged 15-39 years to assess immunity to polio, measles, and rubella and to estimate congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were detected by IgG ELISA and polio antibodies by microneutralization testing. Age-structured catalytic models were fitted to rubella serological data to predict CRS cases. Overall, 29.8% of women lacked immunity to at least one poliovirus (PV); seroprevalence to PV1, PV2 and PV3 was 85.9%, 93.4% and 83.3%, respectively. Rubella and measles antibody seroprevalence was 73.3% and 95.9%, respectively. In the 15-19 years age group, 48.2% [95% confidence interval (CI) 42.4-54.1] were susceptible to either PV1 or PV3, and 40.3% (95% CI 33.0-47.5) to rubella virus. Based on rubella antibody seroprevalence, we estimate that >600 infants are born with CRS in Cambodia annually. Significant numbers of Cambodian women are still susceptible to polio and rubella, especially those aged 15-19 years, emphasizing the need to include adults in VPD surveillance and a potential role for vaccination strategies targeted at adults.

  4. Gene of a new X-linked syndrome with multiple congenital anomalies and severe mental retardation maps in Xp22-pter

    SciTech Connect

    Wittwer, B.; Kircheisen, R.; Leutelt, J.

    1994-09-01

    We report on a family with 3 males presenting with a not yet described new X-chromosomal syndrome of multiple congenital anomalies and severe mental retardation. Two sisters have (with 3 different partners) 3 severely handicapped sons. In each case, oligohydramnios and intrauterine growth retardation were observed. Delivery was in the 34th, 31st, and 38th gestational week, respectively. Two of the patients had microcephaly (head circumference of the third case at birth is unknown). On physical examination, high and broad forehead, frontal bossing, downslanting palpebral fissures, long philtrum, thin upper lip, high arched palate, and deeply set anteverted ears were seen. One of the boys has microphthalmos and sclerocornea, while his cousin shows atrophy of the optic nerve. All three patients show a severe statomotor and mental retardation, they are most likely deaf and blind, have pathologic EEG, and seizures. Important additional findings are hydronephrosis, renal duplication, vesicorenal reflux, and agenesis of corpus callosum. The karyotype is normal (46,XY). We performed a segregation analysis in the family using more than 20 DNA polymorphisms distributed over the X chromosome. Linkage without recombination was found to KAL, DXS278, and DXS16 in Xp22. Analysis of multiple informative meioses suggested a location of the disease locus distal to DXS207. Recombinants were identified with all other marker loci from Xp22-Xpter.

  5. Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.

    PubMed

    Kang, Jiesheng; Chen, Xiao-Liang; Reynolds, William P; Rampe, David

    2007-12-01

    1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.

  6. Constellation of congenital abnormalities in an infant: A new syndrome or tissue-specific mosaicism for trisomy 18?

    SciTech Connect

    Shashi, V.; Golden, W.L.; von Kap-Herr, C.; Wilson, W.G.

    1996-03-01

    A newborn infant born to consanguineous (first cousin) parents was noted to have complex cogenital heart defect and minor anomalies suggestive of trisomy 18. Blood lymphocyte and skin fibroblast karyotypes were normal. He died in the neonatal period of postoperative complications. On interphase fluorescence in-situ hybridization (FISH) using autopsy specimens, a significant number of cells in the liver (17%) were trisomic for chromosome 18, compared to normal control liver tissue. However, interphase FISH analyses of blood lymphocytes, skin fibroblasts, and kidney tissue were normal. It is our opinion that this apparent mosaicism for trisomy 18 in the patient`s liver may be spurious, though it brings into focus the issue of possible tissue/organ-specific mosaicism. The anomalies in this infant do not resemble a previously described malformation syndrome. Parental consanguinity raises the possibility that this represents a new autosomal recessive malformation syndrome. 15 refs., 3 figs., 3 tabs.

  7. Kif7 is required for the patterning and differentiation of the diaphragm in a model of syndromic congenital diaphragmatic hernia

    PubMed Central

    Coles, Garry L.; Ackerman, Kate G.

    2013-01-01

    Congenital diaphragmatic hernia (CDH) is a common birth defect that results in a high degree of neonatal morbidity and mortality, but its pathological mechanisms are largely unknown. Therefore, we performed a forward genetic screen in mice to identify unique genes, models, and mechanisms of abnormal diaphragm development. We identified a mutant allele of kinesin family member 7 (Kif7), the disorganized diaphragm (dd). Embryos homozygous for the dd allele possess communicating diaphragmatic hernias, central tendon patterning defects, and increased cell proliferation with diaphragmatic tissue hyperplasia. Because the patterning of the central tendon is undescribed, we analyzed the expression of genes regulating tendonogenesis in dd/dd mutant embryos, and we determined that retinoic acid (RA) signaling was misregulautted. To further investigate the role of Kif7 and RA signaling in the development of the embryonic diaphragm, we established primary mesenchymal cultures of WT embryonic day 13.5 diaphragmatic cells. We determined that RA signaling is necessary for the expression of tendon markers as well as the expression of other CDH-associated genes. Knockdown of Kif7, and retinoic acid receptors alpha (Rara), beta (Rarb), and gamma (Rarg) indicated that RA signaling is dependent on these genes to promote tendonogenesis within the embryonic diaphragm. Taken together, our results provide evidence for a model in which inhibition of RA receptor signaling promotes CDH pathogenesis through a complex gene network. PMID:23650387

  8. New Genetic Insights into Congenital Heart Disease

    PubMed Central

    Ware, Stephanie M.; Jefferies, John Lynn

    2012-01-01

    There has been remarkable progress in understanding the genetic basis of cardiovascular malformations. Chromosome microarray analysis has provided a new tool to understand the genetic basis of syndromic cardiovascular malformations resulting from microdeletion or microduplication of genetic material, allowing the delineation of new syndromes. Improvements in sequencing technology have led to increasingly comprehensive testing for aortopathy, cardiomyopathy, single gene syndromic disorders, and Mendelian-inherited congenital heart disease. Understanding the genetic etiology for these disorders has improved their clinical recognition and management and led to new guidelines for treatment and family-based diagnosis and surveillance. These new discoveries have also expanded our understanding of the contribution of genetic variation, susceptibility alleles, and epigenetics to isolated congenital heart disease. This review summarizes the current understanding of the genetic basis of syndromic and non-syndromic congenital heart disease and highlights new diagnostic and management recommendations. PMID:22822471

  9. Long-term results of treatment with bosentan in adult Eisenmenger’s syndrome patients with Down’s syndrome related to congenital heart disease

    PubMed Central

    2013-01-01

    Background Patients with Down’s syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down’s syndrome. However, data on the efficacy of PAH-specific therapy in patients with Down’s syndrome are limited. The aim of this retrospective analysis was to determine the long-term efficacy of the dual endothelin receptor antagonist, bosentan, in Eisenmenger's syndrome (ES) patients with Down’s syndrome. Methods In this observational study adults with Down’s syndrome with a confirmed diagnosis of ES (World Health Organization functional class III) and receiving bosentan therapy and were followed up long term. Clinical evaluation at baseline and follow-up visits included resting transcutaneous arterial oxygen saturation and laboratory assessments. Exercise capacity was evaluated using a 6-minute walk test where transcutaneous arterial oxygen saturation at peak exercise (SpO2), 6-minute walk distance (6MWD) and Borg dyspnoea index were assessed. A full echocardiographic assessment was conducted at baseline and follow-up visits. Results Overall, seven adults (mean age 29.6 ± 11.2 years; 57% male) received bosentan at a starting dose of 62.5 mg twice daily. This was increased to the target dose of 125 mg twice daily 4 weeks later. All patients remained on bosentan until the end of the study. After a mean (± standard deviation) duration of 52.2 ± 3.9 months (range: 46.0–55.5 months), 6MWD had increased from 199.6 ± 69.1 metres to 303.7 ± 99.9 metres (P < 0.05) and SpO2 at the end of the 6-minute walk test had increased from 61.6 ± 7.6% to 74.7 ± 6.2% (P < 0.05). Echocardiography demonstrated a significant change in acceleration time from 62.9 ± 11.6 m/s to 83.0 ± 9.6 m/s (P = 0.0156), and acceleration time/ejection time ratio from the pulmonary flow from 0.24 ± 0.04 at baseline to 0.30 ± 0.02 (P = 0.0156) at final follow

  10. Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease.

    PubMed

    Halford, S; Wadey, R; Roberts, C; Daw, S C; Whiting, J A; O'Donnell, H; Dunham, I; Bentley, D; Lindsay, E; Baldini, A

    1993-12-01

    A wide spectrum of birth defects are caused by deletions of the DiGeorge syndrome critical region (DGCR) at human chromosome 22q11. Over one hundred such deletions have now been examined and a minimally deleted region of 300kb defined. Within these sequences we have identified a gene expressed during human and murine embryogenesis. The gene, named TUPLE1, and its murine homologue, encodes a protein containing repeated motifs similar to the WD40 domains found in the beta-transducin/enhancer of split (TLE) family. The TUPLE1 product has several features typical of transcriptional control proteins and in particular has homology with the yeast Tup1 transcriptional regulator. We propose that haploinsufficiency for TUPLE1 is at least partly responsible for DiGeorge syndrome and related abnormalities.

  11. [Congenital torticollis].

    PubMed

    Wicart, P

    2012-03-01

    Congenital torticollis is a very common postural deformity, characterized by a more or less severe retraction of sternocleidomastoid muscle. Any treatment, else that "good sense" counsels given to the parents, is indicated. The evolution is spontaneously favorable in the majority of cases before the age of one year old. The elimination of differential diagnosis (vertebral and/or neurological malformations, ocular, tumor) is the key-point. Screening of congenital hip dislocation is mandatory because the physiopathology is the same in both diseases. A remaining torticolis after 18 months of age may be an indication to sternocleidomastoid muscle lengthening.

  12. A syndrome of hypotonia, psychomotor retardation, seizures, delayed and dysharmonic skeletal maturation, and congenital fibre type disproportion.

    PubMed Central

    Qazi, Q H; Markouizos, D; Rao, C; Sheikh, T; Beller, E; Kula, R

    1994-01-01

    Three unrelated Puerto Rican boys, ranging in age from 3 to 4 years, had marked, central, non-progressive hypotonia, chronic constipation, severe psychomotor retardation, seizures or abnormal electroencephalograph or both, abnormal dermatoglyphics, delayed bone age, dysharmonic skeletal maturation, and preponderance and larger size of type 2 muscle fibres. Additional findings included narrow, high arched palate, prominent nasal root, long philtrum, distended abdomen, and drooling from open mouth. Two of the three patients also had undescended testes, hypertelorism, and tapered fingers. Birth weight, postnatal physical growth, and head size were average. Family and gestational histories and laboratory evaluations were normal. The combination of features observed in the three boys appears to be distinct and to represent a new syndrome. Images PMID:8064821

  13. [A case of neonatal lupus syndrome and congenital atrioventricular block associated with maternal antibodies antiRo/SS-A].

    PubMed

    De Leonibus, C; Lembo, C; Giliberti, P; Rojo, S; Foglia, M C; Giordano, L; Fratta, A

    2012-04-01

    The neonatal lupus erythematosus syndrome (LEN) is a disease due to the transplacental passage of maternal antiextractable nuclear antigens (ENA) antibodies, particularly anti-Ro/SS-A and anti-La/SS-B. The disease affects neonates born from mothers with autoimmune diseases. It is characterized by erythematous annular polycylic skin lesions, slightly scaling with prevalent face localization, hematologic and liver diseases and only in 2% of cases with extracutaneous lesions including complete atrioventricular block. The Authors describe a case of LEN characterized by isolated atrioventricular block at birth and endocardial fibroelastosis without skin lesions in a preterm infant female. She was born from asymptomatic, ANA (Anti-Nuclear Antibodies) and ENA (anti-Extractable Nuclear Antigen) positive mother, with a previous miscarriage at the 5th week of gestation.

  14. [Congenital heart diseases in women].

    PubMed

    Putotto, Carolina; Unolt, Marta; Caiaro, Angela; Marino, Dario; Massaccesi, Valerio; Marino, Bruno; Digilio, Maria Cristina

    2013-02-01

    Are there gender differences in prevalence, surgical results and long-term survival of patients with congenital heart disease? Available literature data allow us to state what follows. At birth there is a mild but significant prevalence of congenital heart disease in females. The most severe congenital heart diseases are less frequent in girls, but when they are present in females, they are linked to a higher surgical mortality rate, due perhaps to lower weight at birth and to the prevalence of extracardiac malformations and/or of associated genetic syndromes. On the other hand, in adults, surgery for congenital heart disease is at higher risk in males, and so the long-term survival rate is higher in females. Particular psychological attitudes, a higher incidence of pulmonary hypertension, as well as specific problems linked to the reproductive function characterize congenital heart disease in adult women. The knowledge and analysis of these data are essential for a correct management of congenital heart disease in neonates, children and adults.

  15. Lateral Diffusion, Function, and Expression of the Slow Channel Congenital Myasthenia Syndrome αC418W Nicotinic Receptor Mutation with Changes in Lipid Raft Components*

    PubMed Central

    Oyola-Cintrón, Jessica; Caballero-Rivera, Daniel; Ballester, Leomar; Baéz-Pagán, Carlos A.; Martínez, Hernán L.; Vélez-Arroyo, Karla P.; Quesada, Orestes; Lasalde-Dominicci, José A.

    2015-01-01

    Lipid rafts, specialized membrane microdomains in the plasma membrane rich in cholesterol and sphingolipids, are hot spots for a number of important cellular processes. The novel nicotinic acetylcholine receptor (nAChR) mutation αC418W, the first lipid-exposed mutation identified in a patient that causes slow channel congenital myasthenia syndrome was shown to be cholesterol-sensitive and to accumulate in microdomains rich in the membrane raft marker protein caveolin-1. The objective of this study is to gain insight into the mechanism by which lateral segregation into specialized raft membrane microdomains regulates the activable pool of nAChRs. We performed fluorescent recovery after photobleaching (FRAP), quantitative RT-PCR, and whole cell patch clamp recordings of GFP-encoding Mus musculus nAChRs transfected into HEK 293 cells to assess the role of cholesterol and caveolin-1 (CAV-1) in the diffusion, expression, and functionality of the nAChR (WT and αC418W). Our findings support the hypothesis that a cholesterol-sensitive nAChR might reside in specialized membrane microdomains that upon cholesterol depletion become disrupted and release the cholesterol-sensitive nAChRs to the pool of activable receptors. In addition, our results in HEK 293 cells show an interdependence between CAV-1 and αC418W that could confer end plates rich in αC418W nAChRs to a susceptibility to changes in cholesterol levels that could cause adverse drug reactions to cholesterol-lowering drugs such as statins. The current work suggests that the interplay between cholesterol and CAV-1 provides the molecular basis for modulating the function and dynamics of the cholesterol-sensitive αC418W nAChR. PMID:26354438

  16. Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review

    PubMed Central

    Vynnycky, Emilia; Adams, Elisabeth J.; Cutts, Felicity T.; Reef, Susan E.; Navar, Ann Marie; Simons, Emily; Yoshida, Lay-Myint; Brown, David W. J.; Jackson, Charlotte; Strebel, Peter M.; Dabbagh, Alya J.

    2016-01-01

    Background The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries. Methods We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000–2010 for each country, region and globally. Results The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4–61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46–195) in the Western Pacific, excluding China, to 116 (95% CI: 56–235) and 121 (95% CI: 31–238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000–80,000) and SE Asia (49,000, 95% CI: 11,000–97,000). In 2010, 105,000 (95% CI: 54,000–158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000–169,000) in 1996. Conclusions Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination. PMID:26962867

  17. Sequence analysis of old and new strains of porcine circovirus associated with congenital tremors in pigs and their comparison with strains involved with postweaning multisystemic wasting syndrome

    PubMed Central

    Choi, Jiwon; Stevenson, Gregory W.; Kiupel, Matti; Harrach, Balázs; Anothayanontha, Lavun; Kanitz, Charles L.; Mittal, Suresh K.

    2002-01-01

    The entire genomes of 7 isolates of porcine circovirus (PCV) from pigs with congenital tremors (CT), type A2, or postweaning multisystemic wasting syndrome (PMWS) were cloned and sequenced. One isolate (CT-PCV-P7) originated from the late 1960s from a neonatal pig with CT, type A2. Two recent PCV isolates (CT-PCV-P5, CT-PCV-P6) were from 2 affected neonatal pigs, from different farms, with unrelated outbreaks of CT; type A2. Four isolates (PMWS-PCV-P1, PMWS-PCV-P2, PMWS-PCV-P3, PMWS-PCV-P4) originated from pigs with PMWS from 4 different farms. A comparative analysis of these PMWS and PCV isolates demonstrated 99% sequence identity with each other, and over 96% sequence identity with previously sequenced PCV2 isolates. The CT-PCV-P5 and CT-PCV-P6 isolates, however, shared 99% of the same identity with each other, and interestingly also with PMWS PCV isolates. There were no consistent genomic differences between PMWS and recent CT isolates. The CT-PCV-P7 showed 98% identity similarity to PK-15-derived PCV1 and demonstrated only 72% identity similarity to either CT-PCV-P5 or CT-PCV-P6. Phylogenetic analysis confirmed that the old isolate (CT-PCV-P7), and the new isolates (CT-PCV-P5, CT-PCV-P6, PMWS-PCV-P1, PMWS-PCV-P2, PMWS-PCV-P3, PMWS-PCV-P4) were correctly classified as PCV1 and PCV2, respectively. PMID:12418776

  18. [Congenital epulis].

    PubMed

    Braga-Tavares, H; Santos, H; M-Pinto, I; Ramos, M; de Sousa, P

    2009-01-01

    Congenital epulis or gingival granular cell tumor is an uncommon benign tumor, usually diagnosed at birth as a pediculated maxilar gingival mass. Although some cases of spontaneous regression have been described, most of the lesions are surgically removed with excelent prognosis and cosmetic final result. The authors describe a case report as well as a short revision on this pathology.

  19. Tracheomalacia - congenital

    MedlinePlus

    ... are floppy. Because the windpipe is the main airway, breathing difficulties begin soon after birth. Congenital tracheomalacia is very uncommon. Symptoms Symptoms can range from mild to severe, and may include: Breathing noises that may change with position and improve during ...

  20. Congenital Defects.

    ERIC Educational Resources Information Center

    Goldman, Allen S.; And Others

    There are two general categories (not necessarily mutually exclusive) of congenital defects: (1) abnormalities that have an hereditary basis, such as single and multiple genes, or chromosomal abberration; and (2) abnormalities that are caused by nonhereditary factors, such as malnutrition, maternal disease, radiation, infections, drugs, or…

  1. Congenital amusias.

    PubMed

    Tillmann, B; Albouy, P; Caclin, A

    2015-01-01

    In contrast to the sophisticated music processing reported in the general population, individuals with congenital amusia show deficits in music perception and production. Congenital amusia occurs without brain damage, sensory or cognitive deficits, and has been suggested as a lifelong deficit with genetic origin. Even though recognized for a long time, this disorder has been systematically studied only relatively recently for its behavioral and neural correlates. The currently most investigated hypothesis about the underlying deficits concerns the pitch dimension, notably with impaired pitch discrimination and memory. Anatomic and functional investigations of pitch processing revealed that the amusic brain presents abnormalities in the auditory and inferior frontal cortices, associated with decreased connectivity between these structures. The deficit also impairs processing of pitch in speech material and processing of the time dimension in music for some of the amusic individuals, but does not seem to affect spatial processing. Some studies suggest at least partial dissociation in the disorder between perception and production. Recent studies revealed spared implicit pitch perception in congenital amusia, supporting the power of implicit cognition in the music domain. Current challenges consist in defining different subtypes of congenital amusia as well as developing rehabilitation programs for this "musical handicap."

  2. Leber's congenital amaurosis: an update.

    PubMed

    Fazzi, Elisa; Signorini, Sabrina Giovanna; Scelsa, Barbara; Bova, Stefania Maria; Lanzi, Giovanni

    2003-01-01

    Leber's congenital amaurosis (LCA) is a clinically and genetically heterogeneous disorder characterized by severe loss of vision at birth. It accounts for 10-18% of cases of congenital blindness. Some patients exhibit only blindness of retinal origin whereas others show evidence of a multi-systemic involvement. We review the literature relating to this severe disorder, highlighting unresolved questions, in particular the nature of the association of LCA with mental retardation and with systemic findings and syndromic pictures. In recent years, genetic advances in the diagnosis of LCA have opened up new horizons, also from a therapeutic point of view. A better understanding of this pathology would be valuable for paediatric neurologists.

  3. Autre cause de mort subite du nourrisson: à propos d'un cas clinique de syndrome du QT long congenital

    PubMed Central

    Seka, Zena; Mols, Pierre; Gobin, Eric; Ngatchou, William

    2014-01-01

    Le syndrome du QT long congénital est une maladie rythmique liée à une mutation génétique et caractérisée par un espace QT allongé sur l’électrocardiogramme, des arythmies malignes type torsade de pointe et fibrillation ventriculaire entraînant une mort subite. Les gènes impliqués dans ces mutations codent pour des sous unités des canaux ioniques responsables de l'activité électrique cardiaque. Le diagnostic est basé sur l’électrocardiogramme, une enquête familiale et l’étude génétique. Le traitement repose sur les bêtabloquants, la sympathectomie et le stimulateur cardiaque. Nous rapportons le cas d'un nourrisson de 2 ans retrouvé en état de mort apparente. Nous discutons de sa prise en charge initiale, de l'enquête familiale et de son suivi ultérieur. PMID:25667708

  4. Craniosynostosis and congenital tracheal anomalies in an infant with Pfeiffer syndrome carrying the W290C FGFR2 mutation.

    PubMed

    Chen, C-P; Lin, S-P; Su, Y-N; Chien, S-C; Tsai, F-J; Wang, W

    2008-01-01

    Pfeiffer syndrome (OMIM 101600) is an autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia, ocular proptosis and digital malformations. We report on a type II Pfeiffer female infant with craniosynostosis, hydrocephalus, and characteristic craniofacial and digital abnormalities. The patient had a history of airway difficulty. Bronchoscopy at age four months revealed low tracheal stenosis and fibrous cartilaginous rings. She underwent tracheostomy for the treatment of cyanotic episodes. Molecular analysis revealed a de novo missense mutation c.870 G>T (TGG>TGT) in the FGFR2 gene that predicts a substitution of cysteine for tryptophan at the codon 290, (W290C). There is phenotypic heterogeneity of tracheal anomalies due to FGFR2 mutations. A review of the literature shows that Pfeiffer patients with the similar tracheal abnormalities can be caused by different FGFR2 mutations and, likewise, the patients with the same FGFR2 mutation may manifest different kinds of tracheal anomalies. Tracheal anomalies may occur in Pfeiffer patients and cause morbidity and mortality because of airway obstruction. Recognition and detailed evaluation of tracheal anomalies should be included in the early diagnostic workup for severe Pfeiffer patients.

  5. Congenital sensorineural hearing loss

    SciTech Connect

    Mafee, M.F.; Selis, J.E.; Yannias, D.A.; Valvassori, G.E.; Pruzansky, S.; Applebaum, E.L.; Capek, V.

    1984-02-01

    The ears of 47 selected patients with congenital sensorineural hearing loss were examined with complex-motion tomography. The patients were divided into 3 general categories: those with a recognized syndrome, those with sensorineural hearing loss unrelated to any known syndrome, and those with microtia. A great variety of inner ear anomalies was detected, but rarely were these characteristic of a particular clinical entity. The most common finding was the Mondini malformation or one of its variants. Isolated dysplasia of the internal auditory canal or the vestibular aqueduct may be responsible for sensorineural hearing loss in some patients. Patients with microtia may also have severe inner ear abnormalities despite the fact that the outer and inner ears develop embryologically from completely separate systems.

  6. Congenital adrenal hyperplasia.

    PubMed

    Merke, Deborah P; Bornstein, Stefan R

    Congenital adrenal hyperplasia (CAH) due to deficiency of 21-hydroxylase is a disorder of the adrenal cortex characterised by cortisol deficiency, with or without aldosterone deficiency, and androgen excess. Patients with the most severe form also have abnormalities of the adrenal medulla and epinephrine deficiency. The severe classic form occurs in one in 15,000 births worldwide, and the mild non-classic form is a common cause of hyperandrogenism. Neonatal screening for CAH and gene-specific prenatal diagnosis are now possible. Standard hormone replacement fails to achieve normal growth and development for many children with CAH, and adults can experience iatrogenic Cushing's syndrome, hyperandrogenism, infertility, or the development of the metabolic syndrome. This Seminar reviews the epidemiology, genetics, pathophysiology, diagnosis, and management of CAH, and provides an overview of clinical challenges and future therapies.

  7. [Congenital ranula].

    PubMed

    Marques, Maria Inês; Morais, Sofia; Coutinho, Sílvia; de Castro, Ochoa; Rei, Ana Isabel

    2010-01-01

    The authors describe a case of congenital ranula diagnosed by a routine prenatal ultrasonography at 21 weeks of gestation. The fetal kariotype was normal. Follow-up ultrasound scans revealed no changes in the size or the position of the cyst. Fetal growth was normal as was the amniotic fluid volume. Surgical treatment was performed 3 days after a normal vaginal delivery, with excellent results.

  8. Congenital Hydrocephalus.

    PubMed

    Estey, Chelsie M

    2016-03-01

    There are several types of hydrocephalus, which are characterized based on the location of the cerebrospinal fluid (CSF) accumulation. Physical features of animals with congenital hydrocephalus may include a dome-shaped skull, persistent fontanelle, and bilateral ventrolateral strabismus. Medical therapy involves decreasing the production of CSF. The most common surgical treatment is placement of a ventriculoperitoneal shunt. Postoperative complications may include infection, blockage, drainage abnormalities, and mechanical failure.

  9. [Congenital aniridia].

    PubMed

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Aniridia is a rare congenital, hereditary, bilateral disease which is associated with various systemic and ocular defects. We present the case of a 61 year old patient who was admitted in the hospital of ophthalmology Cluj Napoca, for the symptoms caused by the ocular defects associated with aniridia. In this case, aniridia is autosomal dominant transmitted with incomplete penetrance and it is not accompanied by any systemic defects. The disease also affects three of her sons and two nephews of the patient.

  10. Hereditary congenital unilateral deafness: a new disorder?

    PubMed

    Dikkers, Frederik G; Verheij, Joke B G M; van Mechelen, Monique

    2005-04-01

    Congenital unilateral deafness is a rare disorder. The prevalence rates are unknown. The prevalence of children with severe to profound hearing losses that are congenital (or acquired before the development of speech and language) is 0.5 to 3 per 1,000 live births. Evidently, congenital unilateral deafness must have a lower prevalence. The purpose of this research was to present a new disorder, hereditary congenital unilateral deafness. A pedigree is presented in which both male and female members display symptoms of congenital unilateral deafness. Two affected persons and a normal-hearing member of the family have vestibular abnormalities without dysequilibrium. The inheritance pattern of this new syndrome is not clear. We hypothesize that the disorder might be new. A family like this has never before been presented in the medical literature.

  11. Congenital anomalies

    PubMed Central

    Kunisaki, Shaun M.

    2012-01-01

    Over the past decade, amniotic fluid-derived stem cells have emerged as a novel, experimental approach for the treatment of a wide variety of congenital anomalies diagnosed either in utero or postnatally. There are a number of unique properties of amniotic fluid stem cells that have allowed it to become a major research focus. These include the relative ease of accessing amniotic fluid cells in a minimally invasive fashion by amniocentesis as well as the relatively rich population of progenitor cells obtained from a small aliquot of fluid. Mesenchymal stem cells, c-kit positive stem cells, as well as induced pluripotent stem cells have all been derived from human amniotic fluid in recent years. This article gives a pediatric surgeon’s perspective on amniotic fluid stem cell therapy for the management of congenital anomalies. The current status in the use of amniotic fluid-derived stem cells, particularly as they relate as substrates in tissue engineering-based applications, is described in various animal models. A roadmap for further study and eventual clinical application is also proposed. PMID:22986340

  12. Congenital Toxoplasmosis

    PubMed Central

    McAuley, James B.

    2014-01-01

    Toxoplasmosis is caused by infection with the parasite Toxoplasma gondii. It is one of the most common parasitic infections in humans and is most typically asymptomatic. However, primary infection in a pregnant woman can cause severe and disabling disease in the developing fetus. Recent developments have included increased understanding of the role of parasite genotype in determining infectivity and disease severity. Risk factors for acquisition of infection have been better defined, and the important role of foodborne transmission has been further delineated. In addition, strategies have emerged to decrease mother-to-child transmission through prompt identification of acutely infected pregnant women followed by appropriate treatment. Refined diagnostic tools, particularly the addition of immunoglobulin G avidity testing, allow for more accurate timing of maternal infection and hence better decision making during pregnancy. Congenitally infected children can be treated, beginning in utero and continuing through the first year of life, to ameliorate the severity of disease. However, despite these many advances in our understanding of congenital toxoplasmosis prevention and treatment, significant areas of study remain: we need better drugs, well defined strategies for screening of pregnant women, improved food safety, and improved diagnostic tests. PMID:25232475

  13. [Congenital insensitivity to pain].

    PubMed

    Danziger, N; Willer, J-C

    2009-02-01

    Congenital insensitivity to pain (CIP) is a rare syndrome with various clinical expressions, characterized by a dramatic impairment of pain perception since birth. In the 1980s, progress in nerve histopathology allowed to demonstrate that CIP was almost always a manifestation of hereditary sensory and autonomic neuropathies (HSAN) involving the small-calibre (A-delta and C) nerve fibres which normally transmit nociceptive inputs along sensory nerves. Identification of the genetic basis of several clinical subtypes has led to a better understanding of the mechanisms involved, emphasizing in particular the crucial role of nerve growth factor (NGF) in the development and survival of nociceptors. Recently, mutations of the gene coding for the sodium channel Nav1.7--a voltage-dependent sodium channel expressed preferentially on peripheral nociceptors and sympathetic ganglia--have been found to be the cause of CIP in patients showing a normal nerve biopsy. This radical impairment of nociception mirrors the hereditary pain syndromes associated with "gain of function" mutations of the same ion channel, such as familial erythromelalgia and paroxysmal extreme pain disorder. Future research with CIP patients may identify other proteins specifically involved in nociception, which might represent potential targets for chronic pain treatment. Moreover, this rare clinical syndrome offers the opportunity to address interesting neuropsychological issues, such as the role of pain experience in the construction of body image and in the empathic representation of others' pain.

  14. DNA methylation abnormalities in congenital heart disease.

    PubMed

    Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A

    2015-01-01

    Congenital heart defects represent the most common malformation at birth, occurring also in ∼50% of individuals with Down syndrome. Congenital heart defects are thought to have multifactorial etiology, but the main causes are largely unknown. We have explored the global methylation profile of fetal heart DNA in comparison to blood DNA from control subjects: an absolute correlation with the type of tissue was detected. Pathway analysis revealed a significant enrichment of differential methylation at genes related to muscle contraction and cardiomyopathies in the developing heart DNA. We have also searched for abnormal methylation profiles on developing heart-tissue DNA of syndromic and non-syndromic congenital heart defects. On average, 3 regions with aberrant methylation were detected per sample and 18 regions were found differentially methylated between groups. Several epimutations were detected in candidate genes involved in growth regulation, apoptosis and folate pathway. A likely pathogenic hypermethylation of several intragenic sites at the MSX1 gene, involved in outflow tract morphogenesis, was found in a fetus with isolated heart malformation. In addition, hypermethylation of the GATA4 gene was present in fetuses with Down syndrome with or without congenital heart defects, as well as in fetuses with isolated heart malformations. Expression deregulation of the abnormally methylated genes was detected. Our data indicate that epigenetic alterations of relevant genes are present in developing heart DNA in fetuses with both isolated and syndromic heart malformations. These epimutations likely contribute to the pathogenesis of the malformation by cis-acting effects on gene expression.

  15. Pellagra revealing a congenital duodenal diaphragm in an adult.

    PubMed

    Khouloud, Bouslama; Haykel, Bedioui; Ahmed, Saidani; Houcine, Maghrebi; Yacine, Ben Safta; Farah, Jokho; Zoubeir, Ben Safta

    2013-12-01

    Pellagra is a nutritional disease caused by the deficiency of niacin. It is a clinical syndrome characterized by four "D's": diarrhea, dermatitis, dementia and ultimately death. We describe a case of pellagra as the initial presentation of congenital duodenal diaphragm.

  16. A patient with congenital hypertrichosis, gum hyperplasia and macromastia.

    PubMed

    Sood, A; Garg, R K; Saily, R; Dash, R J

    2000-05-01

    A syndrome of congenital hypertrichosis, hirsutism, gum hyperplasia and macromastia is described. The patient was demonstrated to have mild hyperinsulinemia with normal oral glucose tolerance test. This is the second such patient reported in the literature.

  17. Associated noncardiac congenital anomalies among cases with congenital heart defects.

    PubMed

    Stoll, Claude; Dott, Beatrice; Alembik, Yves; Roth, Marie-Paule

    2015-02-01

    Cases with congenital heart defects (CHD) often have other associated anomalies. The purpose of this investigation was to assess the prevalence and the types of associated anomalies in CHD in a defined population. The anomalies associated with CHD were collected in all live births, stillbirths and terminations of pregnancy during 26 years in 346,831 consecutive pregnancies of known outcome in the area covered by our population based registry of congenital anomalies. Of the 4005 cases with CHD born during this period (total prevalence of 115.5 per 10,000), 1055 (26.3%) had associated major anomalies. There were 354 (8.8%) cases with chromosomal abnormalities including 218 trisomies 21, and 99 (2.5%) nonchromosomal recognized dysmorphic conditions. There were no predominant recognized dysmorphic conditions, but VACTERL association. However, other recognized dysmorphic conditions were registered including Noonan syndrome, fetal alcohol syndrome, and skeletal dysplasias. Six hundred and two (15.0%) of the cases had non syndromic, non chromosomal multiple congenital anomalies (MCA). Anomalies in the urinary tract, the musculoskeletal, the digestive, and the central nervous systems were the most common other anomalies. Prenatal diagnosis was obtained in 18.7% of the pregnancies. In conclusion the overall prevalence of associated anomalies, which was one in four infants, emphasizes the need for a thorough investigation of cases with CHD. A routine screening for other anomalies may be considered in infants and in fetuses with CHD. One should be aware that the anomalies associated with CHD can be classified into a recognizable anomaly, syndrome or pattern in one out of nine cases with CHD.

  18. Follow-up and diagnostic reappraisal of 75 patients with Leber's congenital amaurosis.

    PubMed

    Lambert, S R; Kriss, A; Taylor, D; Coffey, R; Pembrey, M

    1989-06-15

    We reexamined 75 children in whom Leber's congenital amaurosis had been previously diagnosed. On review, 30 of these patients had an ocular or systemic disorder other than Leber's congenital amaurosis. The most common of these revised diagnoses were congenital stationary night blindness, achromatopsia, infantile-onset retinitis pigmentosa, Joubert's syndrome, Zellweger syndrome, and infantile Refsum's disease. Of the 45 patients with Leber's congenital amaurosis, mental retardation occurred in six patients, and visual deterioration in six patients. Leber's congenital amaurosis should only be diagnosed if other known ocular and systemic disorders have been carefully excluded.

  19. Pulmonary hypertension in congenital shunts.

    PubMed

    Beghetti, Maurice; Tissot, Cecile

    2010-10-01

    Pulmonary arterial hypertension frequently arises in patients with congenital heart disease. The vast majority present with congenital cardiac shunts. Initially these may manifest as left-to-right (i.e. systemic-to-pulmonary) shunts. The natural history of disease progression involves vascular remodeling and dysfunction that lead to increased pulmonary vascular resistance and, finally, to the development of Eisenmenger's syndrome, which is the most advanced form. The anatomical, pathological and structural abnormalities occurring in the pulmonary circulation of these patients are, to some extent, similar to those observed in other forms of pulmonary arterial hypertension. This understanding has recently led to significant changes in the management of Eisenmenger's syndrome, with the introduction of treatment specifically targeting pulmonary vascular disease. Early closure of the cardiac shunt remains the best way of preventing pulmonary vascular lesions. However, it is still not clear which preoperative parameters predict safe and successful repair, though hemodynamic evaluation is still routinely used for assessment. Postoperative pulmonary hypertension, both in the immediate period after surgical repair and during long-term follow-up, remains a real therapeutic challenge. The clinical situation of a single ventricle with Fontan circulation also presents difficulties when pulmonary vascular lesions are present. This article reviews pulmonary hypertension associated with congenital shunts and discusses a number of the specific problems encountered.

  20. Congenital diseases of the gastrointestinal tract.

    PubMed

    Lentze, M

    2014-05-01

    With the rapid increase in knowledge on the genetic origin of diseases within the gastrointestinal tract the number of congenital diseases, which already manifest during childhood have drastically increased. Due to the large application of molecular genetics the number is steadily increasing. To make the access to these rare diseases fast and efficient the data base of the National Library of Medicine (Online Mendelian Inheritance of Man - OMIN) is a very helpful online tool, with which all these disease entities can be found easily (http://www.ncbi.nlm.nih.gov/omim). Detailed tables are given to find most of the congenitally inherited disease, which affect the gastrointestinal tract. A variety of congenital diarrheas with disturbances of digestion, hydrolysis, absorption and secretion is described in detail: lactose intolerance, sucrose intolerance, glucose-galactose malabsorption, fructose malabsorption, trehalase and enterokinase deficiency, congenital chloride and sodium diarrhea, congenital hypomagnesaemia, primary bile acid malabsorption, acrodermatitis enteropathica and Menke's syndrome. Also described in detail are diseases with structural anomalies of the intestine like microvillous inclusion disease, congenital tufting enteropathy and IPEX syndrome. The diagnosis in the disturbances of carbohydrate hydrolysis or absorption can be established by H2-breath tests after appropriate sugar challenge. Treatment consists of elimination of the responsible sugar from the diet. The diagnosis of the congenital secretory diarrheas is established by investigation of electrolytes in blood and stool. Substitution of high doses of the responsible mineral can improve the clinical outcome. In acrodermatitis enteropathica low serum zinc level together with the typical skin lesions guide to the diagnosis. High doses of oral zinc aspartate can cure the symptoms of the disease. The diagnosis of structural congenital lesions of the intestine can be established by histology and

  1. Congenital anomalies associated with congenital hypothyroidism.

    PubMed

    Stoll, C; Dott, B; Alembik, Y; Koehl, C

    1999-01-01

    The French national neonatal screening program for congenital hypothyroidism (CH) was initiated in 1978. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with congenital hypothyroidism (CH) and to compare it with the Northeastern France Birth Defect Monitoring System data from 1979 to 1996. Among 129 CH infants on whom adequate data were available, 20 infants (15.5%) had associated congenital anomalies. Eight out of 76 infants with persistent CH had ETAs (10.5%) whereas 12 out of 53 children with transient hypothyroidism had ETAs (22.6%, p < 0.05). Some additional anomalies were considerably more common than in the general population. Nine infants had congenital cardiac anomalies (6.9%). This rises the question if teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETAs.

  2. Sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus syndrome.

    PubMed

    Hsieh, Chih-Wei; Wu, Yu-Hung; Lin, Shuan-Pei; Peng, Chun-Chih; Ho, Che-Sheng

    2012-01-01

    SCALP syndrome is an acronym describing the coincidence of sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus). We present a fourth case of this syndrome.

  3. Mardini-Nyhan association (lung agenesis, congenital heart, and thumb anomalies): three new cases and possible recurrence in a sib-is there a distinct recessive syndrome?

    PubMed

    Hastings, Rob; Harding, David; Donaldson, Alan; Liebling, Rachel; Hayes, Alison; Kraus, Alison; Joss, Shelagh; Narayanaswamy, Shuba; Turnpenny, Peter; Smithson, Sarah

    2009-12-01

    In 1985, Mardini and Nyhan described three patients from consanguineous families with unilateral complete/partial lung agenesis, congenital cardiac defects, and ipsilateral thumb anomalies. Although there have been many reports of lung agenesis with other malformations, especially hemifacial microsomia and radial ray anomalies, very few demonstrate this triad of defects. We describe three patients with the Mardini-Nyhan association which may represent a distinct entity, although this remains uncertain at present. A fourth patient is also described, the sister of one of the other patients, with complex congenital cardiac disease and bilateral lung lobation abnormalities. This is the first reported incidence of a possible recurrence within a family and suggests, together with the consanguinity observed by Mardini and Nyhan, that recessive inheritance should be considered in genetic counseling for this disorder.

  4. Congenital Heart Disease in Adults

    MedlinePlus

    ... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...

  5. Spontaneously regressing leukoencephalopathy with bilateral temporal cysts in congenital rubella infection.

    PubMed

    Severino, Mariasavina; Zerem, Ayelet; Biancheri, Roberta; Cristina, Emilio; Rossi, Andrea

    2014-04-01

    Very little is known regarding neuroimaging findings in patients with congenital rubella syndrome. We report a 1.9-year-old boy with congenital rubella syndrome who presented in the neonatal period with severe multisystem involvement and diffuse leukoencephalopathy with subcortical anterior temporal cysts, which showed spontaneous improvement during a period of 3 years.

  6. Congenital myopathies

    PubMed Central

    Colombo, Irene; Scoto, Mariacristina; Manzur, Adnan Y.; Robb, Stephanie A.; Maggi, Lorenzo; Gowda, Vasantha; Cullup, Thomas; Yau, Michael; Phadke, Rahul; Sewry, Caroline; Jungbluth, Heinz

    2015-01-01

    Objective: To assess the natural history of congenital myopathies (CMs) due to different genotypes. Methods: Retrospective cross-sectional study based on case-note review of 125 patients affected by CM, followed at a single pediatric neuromuscular center, between 1984 and 2012. Results: Genetic characterization was achieved in 99 of 125 cases (79.2%), with RYR1 most frequently implicated (44/125). Neonatal/infantile onset was observed in 76%. At birth, 30.4% required respiratory support, and 25.2% nasogastric feeding. Twelve percent died, mainly within the first year, associated with mutations in ACTA1, MTM1, or KLHL40. All RYR1-mutated cases survived and did not require long-term ventilator support including those with severe neonatal onset; however, recessive cases were more likely to require gastrostomy insertion (p = 0.0028) compared with dominant cases. Independent ambulation was achieved in 74.1% of all patients; 62.9% were late walkers. Among ambulant patients, 9% eventually became wheelchair-dependent. Scoliosis of variable severity was reported in 40%, with 1/3 of (both ambulant and nonambulant) patients requiring surgery. Bulbar involvement was present in 46.4% and required gastrostomy placement in 28.8% (at a mean age of 2.7 years). Respiratory impairment of variable severity was a feature in 64.1%; approximately half of these patients required nocturnal noninvasive ventilation due to respiratory failure (at a mean age of 8.5 years). Conclusions: We describe the long-term outcome of a large cohort of patients with CMs. While overall course is stable, we demonstrate a wide clinical spectrum with motor deterioration in a subset of cases. Severity in the neonatal/infantile period is critical for survival, with clear genotype-phenotype correlations that may inform future counseling. PMID:25428687

  7. [Genetics of congenital cardiopathies].

    PubMed

    Moreno García, M; Gómez Rodríguez, M J; Barreiro Miranda, E

    2000-07-01

    Congenital heart malformations are the most common of all birth defects, affecting 0.5-1% of all live births. Some of these malformations are due to genetic anomalies. Patterns of autosomal dominant, autosomal recessive and X-linked inheritance have been described. Mitochondrial inheritance and chromosomal anomalies can also be responsible for congenital heart malformations. Several genes for congenital heart defects have been identified. We review current knowledge on the genetic etiology of congenital heart disease.

  8. Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

    PubMed Central

    Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

    1998-01-01

    The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43. PMID:9634513

  9. De novo 9q gain in an infant with tetralogy of Fallot with absent pulmonary valve: Patient report and review of congenital heart disease in 9q duplication syndrome.

    PubMed

    Amarillo, Ina E; O'Connor, Shawn; Lee, Caroline K; Willing, Marcia; Wambach, Jennifer A

    2015-12-01

    Genomic disruptions, altered epigenetic mechanisms, and environmental factors contribute to the heterogeneity of congenital heart defects (CHD). In recent years, chromosomal microarray analysis (CMA) has led to the identification of numerous copy number variations (CNV) in patients with CHD. Genes disrupted by and within these CNVs thus represent excellent candidate genes for CHD. Microduplications of 9q (9q+) have been described in patients with CHD, however, the critical gene locus remains undetermined. Here we discuss an infant with tetralogy of Fallot with absent pulmonary valve, fetal hydrops, and a 3.76 Mb de novo contiguous gain of 9q34.2-q34.3 detected by CMA, and confirmed by karyotype and FISH studies. This duplicated interval disrupted RXRA (retinoid X receptor alpha; OMIM #180245) at intron 1. We also review CHD findings among previously reported patients with 9q (9q+) duplication syndrome. This is the first report implicating RXRA in CHD with 9q duplication, providing additional data in understanding the genetic etiology of tetralogy of Fallot, CHD, and disorders linked to 9q microduplication syndrome. This report also highlights the significance of CMA in the clinical diagnosis and genetic counseling of patients and families with complex CHD.

  10. Congenital dystrophic medial rectus muscles

    PubMed Central

    Murthy, Ramesh

    2017-01-01

    We report two patients, one with congenital dystrophic medial rectus muscles and one with absence of the medial rectus muscles; in addition, one of them had absence of the lateral rectus muscles. While absence of the superior oblique and superior rectus has been more commonly reported in literature, especially with craniofacial syndromes, our patients were nonsyndromic. Considering the risk of anterior segment ischemia, correction of the large-angle exotropia was performed by horizontal rectus muscle surgery where possible, along with transfer of the superior oblique tendon to the superior part of the normal medial rectus muscle insertion area to create a tethering effect with a good outcome. PMID:28300745

  11. X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome.

    PubMed

    Møller, R S; Jensen, L R; Maas, S M; Filmus, J; Capurro, M; Hansen, C; Marcelis, C L M; Ravn, K; Andrieux, J; Mathieu, M; Kirchhoff, M; Rødningen, O K; de Leeuw, N; Yntema, H G; Froyen, G; Vandewalle, J; Ballon, K; Klopocki, E; Joss, S; Tolmie, J; Knegt, A C; Lund, A M; Hjalgrim, H; Kuss, A W; Tommerup, N; Ullmann, R; de Brouwer, A P M; Strømme, P; Kjaergaard, S; Tümer, Z; Kleefstra, T

    2014-05-01

    Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.

  12. Whole Genome Sequencing Reveals Novel Non-Synonymous Mutation in Ectodysplasin A (EDA) Associated with Non-Syndromic X-Linked Dominant Congenital Tooth Agenesis

    PubMed Central

    Sarkar, Tanmoy; Bansal, Rajesh; Das, Parimal

    2014-01-01

    Congenital tooth agenesis in human is characterized by failure of tooth development during tooth organogenesis. 300 genes in mouse and 30 genes in human so far have been known to regulate tooth development. However, candidature of only 5 genes viz. PAX9, MSX1, AXIN2, WNT10A and EDA have been experimentally established for congenitally missing teeth like hypodontia and oligodontia. In this study an Indian family with multiple congenital tooth agenesis was identified. Pattern of inheritance was apparently autosomal dominant type with a rare possibility to be X-linked. Whole genome sequencing of two affected individuals was carried out which revealed 119 novel non-synonymous single nucleotide variations (SNVs) distributed among 117 genes. Out of these only one variation (c.956G>T) located at exon 9 of X-linked EDA gene was considered as pathogenic and validated among all the affected and unaffected family members and unrelated controls. This variation leads to p.Ser319Ile change in the TNF homology domain of EDA (transcript variant 1) protein. In silico analysis predicts that this Ser319 is well conserved across different vertebrate species and a part of putative receptor binding site. Structure based homology modeling predicts that this amino acid residue along with four other amino acid residues nearby, those when mutated known to cause selective tooth agenesis, form a cluster that may have functional significance. Taken together these results suggest that c.956G>T (p.Ser319Ile) mutation plausibly reduces the receptor binding activity of EDA leading to distinct tooth agenesis in this family. PMID:25203534

  13. JS-X syndrome: A multiple congenital malformation with vocal cord paralysis, ear deformity, hearing loss, shoulder musculature underdevelopment, and X-linked recessive inheritance.

    PubMed

    Hoeve, Hans L J; Brooks, Alice S; Smit, Liesbeth S

    2015-07-01

    We report on a family with a not earlier described multiple congenital malformation. Several male family members suffer from laryngeal obstruction caused by bilateral vocal cord paralysis, outer and middle ear deformity with conductive and sensorineural hearing loss, facial dysmorphisms, and underdeveloped shoulder musculature. The affected female members only have middle ear deformity and hearing loss. The pedigree is suggestive of an X-linked recessive inheritance pattern. SNP-array revealed a deletion and duplication on Xq28 in the affected family members. A possible aetiology is a neurocristopathy with most symptoms expressed in structures derived from branchial arches.

  14. Congenital chylothorax in newborn with trisomy 21.

    PubMed

    Lomauri, Kh

    2014-11-01

    Neonatal chylothorax results from the accumulation of chyle in the pleural space and may be either congenital or an acquired condition. Congenital chylothorax is most likely due to abnormal development or obstruction of the lymphatic system. It is often associated with hydrops fetalis. It can be idiopathic or may be associated with various chromosomal anomalies including Trisomy 21, Turner syndrome, Noonan syndrome, and other genetic abnormalities. Congenital pulmonary lymphangiectasia and generalized lymphangiomatosis have also been reported to be associated with congenital chylothorax. Several case reports indicate that congenital chylothorax can recur in subsequent offspring, suggesting a possible underlying genetic etiology. It is important to identify infants with chylothorax, as there are specific issues that need to be addressed in the management of these patients. We present a case of newborn with trysomy 21 (trisomy 21 was diagnosed antenatally by amniocentesis with support of Association "Perinatology"), who developed moderate Respiratory Distress Syndrome, chest X-ray and US reveal pleural effusion on right side rapid intervention was made before deterioration, requiring intensive life-saving measures. In the neonate, chylous effusion is not a common cause of pleural effusions. It is characterized as an exudate because of the high protein and lipid content once the infant is fed. The fluid will be clear/yellow to slightly cloudy in the unfed state and will quickly become milky following feeding, as chylomicrons appear in the fluid. Lymphocytes predominate in the differential cell count of chyle. The volume of fluid output can be high, and management can be challenging. We review the common manifestations of congenital chylotoraxes and emphasize the importance of early diagnosis and intervention in preventing devastating outcomes from this condition.

  15. Noonan syndrome.

    PubMed

    Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

    2013-01-26

    Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS-MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype-phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments.

  16. Congenital glaucoma in cutis marmorata teleangiectatica congenita.

    PubMed

    Mayatepek, E; Krastel, H; Völcker, H E; Pfau, B; Almasan, K

    1991-01-01

    A case of congenital glaucoma in cutis marmorata teleangiectatica congenita (CMTC, van Lohuizen syndrome) is described. The cutaneous anomaly and heterochromia iridium were noticed at birth. Brown discoloration of one iris was due to iris anterior layer dysplasia, resulting in unilateral glaucoma. Two trabeculotomies were performed until persistent normalization of intraocular pressure could be achieved. The possibility of a genetic basis and hereditary condition of CMTC and its association with congenital glaucoma is discussed. Patients with CMTC should regularly undergo ophthalmological follow-up to rule out development of glaucoma.

  17. Congenital Minamata disease: warnings from Japan's experience.

    PubMed

    Kondo, K

    2000-07-01

    Minamata disease is alkylmercury poisoning causing Hunter-Russell syndrome due to ingestion of seafood polluted by industrial waste. Two epidemics occurred in Minamata (1956) and Niigata (1965), Japan. Many infants with "cerebral palsy" in villages where adult cases occurred were established as having congenital Minamata disease. Developing brains were affected by alkylmercury through transplacental exposure and even by breastfeeding. This report reviews the history, clinical features, pathology, epidemiology, metal analysis, experiments, and sociolegal aspects of congenital Minamata disease. Many victims are still alive and their present conditions are reviewed.

  18. X-linked neurodegenerative syndrome with congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration, linked to Xp22.33-pter

    SciTech Connect

    Portes, V. des; Beldjord, C.; Bruels, T.

    1996-07-12

    Linkage analysis was performed in a previously described family segregating for an X-linked progressive neurological disorder. In three generations, the disease was inherited from the mothers in seven affected males. Five had severe congenital hypotonia and died during the first year of life. Two other boys (maternal cousins) were found to have severe congenital ataxia, late-onset progressive myoclonic encephalopathy, and selective macular degeneration; brain CT-scan showed moderate cerebellar vermis hypoplasia. Linkage analysis was carried out in 12 informative relatives using 35 microsatellite markers (Genethon) evenly distributed on the X chromosome. A multipoint analysis showed a significant linkage (Z > 2) between the disease and three markers in the Xp22.33 region: DYS403 (Z = 2.37, {theta} = 0) which maps in the pseudoautosomal region, DXS7099 (Z = 2.45, {theta} = 0), and DXS7100 (Z = 2.48, {theta} = 0). Further linkage analysis with more telomeric markers will refine the location of this severe X-linked encephalopathy. 12 refs., 2 figs., 1 tab.

  19. Arachnodactyly, aminoaciduria, congenital cataracts, cerebellar ataxia, and delayed developmental milestones

    PubMed Central

    Bhaskar, P. A.; Jagannathan, K.; Valmikinathan, K.

    1974-01-01

    Two male cousins are reported with arachnodactyly, selective aminoaciduria, congenital cataracts, cerebellar ataxia, and delayed developmental milestones, and a distant female relative with similar abnormalities. The syndrome is thought to be previously undescribed, though it has resemblances to Marinesco-Sjögren and Marfan's syndromes. Images PMID:4448994

  20. Congenital insensitivity to pain: report of two cases.

    PubMed

    Lawoyin, J O; Lawoyin, D O

    2001-01-01

    Congenital indifference or insensitivity to pain (CIP) is a rare syndrome. It mimics a number of other syndromes categorized under peripheral sensory neuropathies, often making early diagnosis difficult. Two cases from the middle east are presented, highlighting possible diagnostic, and management difficulties.

  1. Congenital Portosystemic Shunt: Our Experience

    PubMed Central

    Timpanaro, Tiziana; Passanisi, Stefano; Sauna, Alessandra; Trombatore, Claudia; Pennisi, Monica; Petrillo, Giuseppe; Smilari, Pierluigi; Greco, Filippo

    2015-01-01

    Introduction. Congenital portosystemic venous malformations are rare abnormalities in which the portal blood drains into a systemic vein and which are characterized by extreme clinical variability. Case Presentations. The authors present two case reports of a congenital extrahepatic portosystemic shunt (Type II). In the first patient, apparently nonspecific symptoms, such as headache and fatigue, proved to be secondary to hypoglycemic episodes related to the presence of a portosystemic shunt, later confirmed on imaging. During portal vein angiography, endovascular embolization of the portocaval fistula achieved occlusion of the anomalous venous tract. In the second patient, affected by Down's syndrome, the diagnosis of a portosystemic malformation was made by routine ultrasonography, performed to rule out concurrent congenital anomalies. Because of the absence of symptoms, we chose to observe this patient. Conclusions. These two case reports demonstrate the clinical heterogeneity of this malformation and the need for a multidisciplinary approach. As part of a proper workup, clinical evaluation must always be followed by radiographic diagnosis. PMID:25709849

  2. Congenital Diaphragmatic Hernia

    PubMed Central

    2012-01-01

    Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted. PMID:22214468

  3. Congenital vascular malformation associated with multiple cranial, vertebral and upper limb skeletal abnormalities.

    PubMed

    Marsden, N; Shokrollahi, K; Maw, K; Sierakowski, A; Bhat, F A; Mathur, B

    2010-07-01

    The association between congenital vascular malformations and altered bone growth, the so-called vascular bone syndrome, is well documented. Various eponymous syndromes each with their individual traits, such as Klippel-Trenaunay, Parkes-Weber and Servelle-Martorell syndrome have been described, along with variations. We report on a previously undescribed case of congenital vascular malformation associated with multiple skeletal abnormalities affecting the skull, vertebrae and right upper limb, and discuss the literature.

  4. Congenital narrowing of the cervical spinal canal.

    PubMed Central

    Kessler, J T

    1975-01-01

    The clinical and laboratory findings in six patients with congenital narrowing of the cervical spinal canal and neurological symptoms are described. A variable age of onset and an entirely male occurrence were found. Signs and symptoms of spinal cord dysfunction predominated in all but one patient. Symptoms were produced in five patients by increased physical activity alone. Congenital narrowing of the cervical spinal canal may result in cord compression without a history of injury and occasionally without evidence of significant bony degenerative changes. The clinical features may be distinguishable from those found in cervical spondylosis without congenital narrowing. Intermittent claudication of the cervical spinal cord appears to be an important feature of this syndrome. Surgery improved four out of five people. PMID:1219087

  5. Treatment of Common Congenital Hand Conditions

    PubMed Central

    Oda, Takashi; Pushman, Allison G.; Chung, Kevin C.

    2015-01-01

    Objective After reading this article, the participant should be able to: 1. Recognize the clinical features associated with five common congenital hand conditions. 2. Describe the indications and appropriate timing for various surgical procedures used to treat congenital hand anomalies. 3. Identify the pearls and pitfalls of these surgical treatments in order to avoid complications. 4. Understand the expected post-operative outcomes associated with these surgical procedures. Summary This article will provide an introduction to congenital hand differences by focusing on practical surgical strategies for treating five commonly encountered conditions including syndactyly, constriction ring syndrome, duplicated thumb, hypoplastic thumb and trigger thumb. The accompanying videos will demonstrate common and reliable surgical techniques for syndactyly release, duplicated thumb reconstruction and pollicization for hypoplastic thumb. PMID:20811188

  6. Congenital malformations of the brain and spine.

    PubMed

    Shankar, Prashant; Zamora, Carlos; Castillo, Mauricio

    2016-01-01

    In this chapter we briefly address the most common congenital brain and spinal anomalies as well as their most salient imaging, especially magnetic resonance, findings. Some of them, such as Chiari II, and open spinal defects, have become relatively rare due to their detection in utero and repair of the spinal malformation. Regardless of the type of brain anomaly, the most common clinical symptoms are mental retardation, hydrocephalus, and seizure; the latter two may need to be surgically and medically addressed. The most commonly found spinal congenital anomalies include the filum terminale lipoma which is generally asymptomatic and incidental and the caudal regression syndrome for which no primary treatment exists. Any spinal congenital anomaly may present in adulthood as a consequence of spinal cord tethering and/or development of syringomyelia.

  7. Xenopus: An Emerging Model for Studying Congenital Heart Disease

    PubMed Central

    Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.

    2011-01-01

    Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes. PMID:21538812

  8. Congenital defects of sheep.

    PubMed

    Dennis, S M

    1993-03-01

    With increasing incrimination of viruses, plants, and drugs as causes of ovine congenital defects, concerted efforts are required to identify environmental teratogens. Expanding knowledge of congenital defects requires studying as many defective lambs as possible; recording and documenting; detailed diagnostic examinations; genetic analyses and chromosomal examinations, whenever possible; and field investigations. Adopting standardized classification, terminology, and diagnostic procedures should improve descriptions, diagnoses, and interdisciplinary exchange of information. That, in turn, should improve our knowledge of and diagnosis of congenital defects of sheep in the future. Finally, veterinary clinicians and diagnosticians are encouraged to take an interest in congenital defects and teratology.

  9. Genetics Home Reference: congenital hypothyroidism

    MedlinePlus

    ... Understand Genetics Home Health Conditions congenital hypothyroidism congenital hypothyroidism Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Congenital hypothyroidism is a partial or complete loss of function ...

  10. A de novo 2q35-q36.1 deletion incorporating IHH in a Chinese boy (47,XYY) with syndactyly, type III Waardenburg syndrome, and congenital heart disease.

    PubMed

    Wang, D; Ren, G F; Zhang, H Z; Yi, C Y; Peng, Z J

    2016-12-02

    Reports of terminal and interstitial deletions of the long arm of chromosome 2 are rare in the literature. Here, we present a case report concerning a Chinese boy with a 47,XYY karyotype and a de novo deletion comprising approximately 5 Mb between 2q35 and q36.1, along with syndactyly, type III Waardenburg syndrome, and congenital heart disease. High-resolution chromosome analysis to detect copy number variations was carried out using an Affymetrix microarray platform, and the genes affected by the patient's deletion, including IHH, were determined. However, no copy number changes were observed in his healthy parents. The present case exhibited novel syndactyly features, broadening the spectrum of clinical findings observed in individuals with 2q interstitial deletions. Our data, together with previous observations, suggest that IHH haploinsufficiency is the principal pathogenic factor in the syndactyly phenotype in this study, and that different types of variations at the IHH locus may cause divergent disease phenotypes. This is the first report of the involvement of IHH haploinsufficiency in syndactyly phenotype.

  11. Alternative splicing of exon 17 and a missense mutation in exon 20 of the insulin receptor gene in two brothers with a novel syndrome of insulin resistance (congenital fiber-type disproportion myopathy).

    PubMed

    Vorwerk, P; Christoffersen, C T; Müller, J; Vestergaard, H; Pedersen, O; De Meyts, P

    1999-01-01

    The insulin receptor (IR) in two brothers with a rare syndrome of congenital muscle fiber type disproportion myopathy (CFTDM) associated with diabetes and severe insulin resistance was studied. By direct sequencing of Epstein-Barr virus-transformed lymphocytes both patients were found to be compound heterozygotes for mutations in the IR gene. The maternal allele was alternatively spliced in exon 17 due to a point mutation in the -1 donor splice site of the exon. The abnormal skipping of exon 17 shifts the amino acid reading frame and leads to a truncated IR, missing the entire tyrosine kinase domain. In the correct spliced variant, the point mutation is silent and results in a normally translated IR. The paternal allele carries a missense mutation in the tyrosine kinase domain. All three cDNA variants were present in the lymphocytes of the patients. Purified IR from 293 cells overexpressing either of the two mutated receptors lacked basal or stimulated IR beta-subunit autophosphorylation. A third brother who inherited both normal alleles has an normal muscle phenotype and insulin sensitivity, suggesting a direct linkage of these IR mutations with the CFTDM phenotype.

  12. Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: Outflow tract obstruction, coarctation of the aorta, tetralogy of Fallot, Ebstein anomaly and Marfan’s syndrome

    PubMed Central

    Silversides, Candice K; Beauchesne, Luc; Bradley, Timothy; Connelly, Michael; Niwa, Koichiro; Mulder, Barbara; Webb, Gary; Colman, Jack; Therrien, Judith

    2010-01-01

    With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part II of the guidelines includes recommendations for the care of patients with left ventricular outflow tract obstruction and bicuspid aortic valve disease, coarctation of the aorta, right ventricular outflow tract obstruction, tetralogy of Fallot, Ebstein anomaly and Marfan’s syndrome. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org. PMID:20352138

  13. A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation

    PubMed Central

    Castori, Marco; Bottillo, Irene; D'Angelantonio, Daniela; Morlino, Silvia; De Bernardo, Carmelilia; Scassellati Sforzolini, Giovanna; Silvestri, Evelina; Grammatico, Paola

    2014-01-01

    Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype. PMID:25337072

  14. A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

    PubMed

    Castori, Marco; Bottillo, Irene; D'Angelantonio, Daniela; Morlino, Silvia; De Bernardo, Carmelilia; Scassellati Sforzolini, Giovanna; Silvestri, Evelina; Grammatico, Paola

    2014-08-01

    Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype.

  15. Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract.

    PubMed

    Zhang, D D; Du, J Z; Topolewski, J; Wang, X M

    2016-07-29

    Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the X or Y chromosome. Congenital cataract is a symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome. On the other hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract. This could help identify novel approaches for the prevention, early diagnosis, and comprehensive disease treatment.

  16. The emerging role of genomics in the diagnosis and workup of congenital urinary tract defects: a novel deletion syndrome on chromosome 3q13.31-22.1

    PubMed Central

    Materna-Kiryluk, Anna; Kiryluk, Krzysztof; Burgess, Katelyn E; Bieleninik, Arkadiusz; Sanna-Cherchi, Simone; Gharavi, Ali G.; Latos-Bielenska, Anna

    2014-01-01

    Background Copy number variants (CNVs) are increasingly recognized as an important cause of congenital malformations and likely explain over 16% cases of CAKUT. Here, we illustrate how a molecular diagnosis of CNV can inform the clinical management of a pediatric patient presenting with CAKUT and other organ defects. Methods We describe a 14 year-old girl with a large de novo deletion of chromosome 3q13.31-22.1 that disrupts 101 known genes and manifests with CAKUT, neurodevelopmental delay, agenesis of corpus callosum (ACC), cardiac malformations, electrolyte and endocrine disorders, skeletal abnormalities and dysmorphic features. We perform extensive annotation of the deleted region to prioritize genes for specific phenotypes and to predict future disease risk. Results Our case defined new minimal chromosomal candidate regions for both CAKUT and ACC. Moreover, the presence of the CASR gene in the deleted interval predicted a diagnosis of hypocalciuric hypercalcemia, which was confirmed by serum and urine chemistries. Our gene annotation explained clinical hypothyroidism and predicted that the index case is at increased risk of thoracic aortic aneurysm, renal cell carcinoma and myeloproliferative disorder. Conclusions Extended annotation of CNV regions refines diagnosis and uncovers previously unrecognized phenotypic features. This approach enables personalized treatment and prevention strategies in patients harboring genomic deletions. PMID:24292865

  17. Chronic pro-oxidative state and mitochondrial dysfunctions are more pronounced in fibroblasts from Down syndrome foeti with congenital heart defects.

    PubMed

    Piccoli, Claudia; Izzo, Antonella; Scrima, Rosella; Bonfiglio, Ferdinando; Manco, Rosanna; Negri, Rosa; Quarato, Giovanni; Cela, Olga; Ripoli, Maria; Prisco, Marina; Gentile, Flaviana; Calì, Gaetano; Pinton, Paolo; Conti, Anna; Nitsch, Lucio; Capitanio, Nazzareno

    2013-03-15

    Trisomy of chromosome 21 is associated to congenital heart defects in ∼50% of affected newborns. Transcriptome analysis of hearts from trisomic human foeti demonstrated that genes involved in mitochondrial function are globally downregulated with respect to controls, suggesting an impairment of mitochondrial function. We investigated here the properties of mitochondria in fibroblasts from trisomic foeti with and without cardiac defects. Together with the upregulation of Hsa21 genes and the downregulation of nuclear encoded mitochondrial genes, an abnormal mitochondrial cristae morphology was observed in trisomic samples. Furthermore, impairment of mitochondrial respiratory activity, specific inhibition of complex I, enhanced reactive oxygen species production and increased levels of intra-mitochondrial calcium were demonstrated. Seemingly, mitochondrial dysfunction was more severe in fibroblasts from cardiopathic trisomic foeti that presented a more pronounced pro-oxidative state. The data suggest that an altered bioenergetic background in trisomy 21 foeti might be among the factors responsible for a more severe phenotype. Since the mitochondrial functional alterations might be rescued following pharmacological treatments, these results are of interest in the light of potential therapeutic interventions.

  18. Pregnancy and Adult Congenital Heart Disease.

    PubMed

    Bhatt, Ami B; DeFaria Yeh, Doreen

    2015-11-01

    Most women with known congenital heart disease can have successful pregnancy, labor, and delivery. Preconception assessment is essential in understanding anatomy, repairs, and current physiology, all of which can influence risk in pregnancy. With that foundation, a multidisciplinary cardio-obstetric team can predict and prepare for complications that may occur with superimposed hemodynamic changes of pregnancy. Individuals with Eisenmenger syndrome, pulmonary hypertension, cyanosis, significant left heart obstruction, ventricular dysfunction, or prior major cardiac event are among the highest risk for complications.

  19. Severe congenital malaria acquired in utero.

    PubMed

    Poespoprodjo, Jeanne R; Hasanuddin, Afdal; Fobia, Wendelina; Sugiarto, Paulus; Kenangalem, Enny; Lampah, Daniel A; Tjitra, Emiliana; Price, Ric N; Anstey, Nicholas M

    2010-04-01

    Vertical transmission of Plasmodium falciparum is under-recognized and usually associated with asymptomatic low-level parasitemia at birth. We report symptomatic congenital malaria presenting as a neonatal sepsis syndrome. The presence at birth of a high asexual parasitemia, gametocytemia, and splenomegaly indicated in utero rather than intrapartum transmission. The neonate was successfully treated with intravenous artesunate followed by oral dihydroartemisinin-piperaquine, without apparent adverse effects.

  20. Myasthenic Crisis in an Elderly Patient with Positive Antibodies against Acetylcholine and Anti-MuSK, Successfully Treated with Noninvasive Mechanical Ventilation

    PubMed Central

    Fernández, José A.; Fernández-Valiñas, Antonio; Hernández, Daniel; Orozco, Joel; Lugo, Antonio

    2015-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness. Subjects with antibodies against acetylcholine usually have greater ocular symptoms, lower bulbar weakness, and fewer respiratory complications, compared to individuals with anti-MuSK antibodies. The presence of positivity to both types of antibodies in the same patient is uncommon, and the clinical behavior of these individuals is uncertain. A myasthenic crisis is characterized by respiratory and bulbar muscle weakness, causing acute respiratory failure which requires mechanical ventilatory support. We present the case of a 73-year-old man with a medical history of myasthenia gravis and positive antibody titers against acetylcholine and anti-MuSK, who sought for medical assessment because of respiratory tract infection symptoms, dysphagia, and generalized weakness. Initially, no respiratory distress was found. After 24 hours the patient showed respiratory deterioration and neurological impairment. Endotracheal intubation was rejected, so ventilatory support with noninvasive ventilation was started. The patient was supported by intense respiratory therapy, and infusion of immunoglobulin was initiated. The individual responded favorably, improving his general condition. Weaning from noninvasive mechanical ventilation was possible after six days. Our case illustrates that noninvasive ventilation, properly supported by intense respiratory therapy, can be a great option to avoid intubation in the myasthenic patient. PMID:26783473

  1. Myasthenic Crisis in an Elderly Patient with Positive Antibodies against Acetylcholine and Anti-MuSK, Successfully Treated with Noninvasive Mechanical Ventilation.

    PubMed

    Fernández, José A; Fernández-Valiñas, Antonio; Hernández, Daniel; Orozco, Joel; Lugo, Antonio

    2015-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness. Subjects with antibodies against acetylcholine usually have greater ocular symptoms, lower bulbar weakness, and fewer respiratory complications, compared to individuals with anti-MuSK antibodies. The presence of positivity to both types of antibodies in the same patient is uncommon, and the clinical behavior of these individuals is uncertain. A myasthenic crisis is characterized by respiratory and bulbar muscle weakness, causing acute respiratory failure which requires mechanical ventilatory support. We present the case of a 73-year-old man with a medical history of myasthenia gravis and positive antibody titers against acetylcholine and anti-MuSK, who sought for medical assessment because of respiratory tract infection symptoms, dysphagia, and generalized weakness. Initially, no respiratory distress was found. After 24 hours the patient showed respiratory deterioration and neurological impairment. Endotracheal intubation was rejected, so ventilatory support with noninvasive ventilation was started. The patient was supported by intense respiratory therapy, and infusion of immunoglobulin was initiated. The individual responded favorably, improving his general condition. Weaning from noninvasive mechanical ventilation was possible after six days. Our case illustrates that noninvasive ventilation, properly supported by intense respiratory therapy, can be a great option to avoid intubation in the myasthenic patient.

  2. Multifocal Congenital Hemangiopericytoma.

    PubMed

    Robl, Renata; Carvalho, Vânia Oliveira; Abagge, Kerstin Taniguchi; Uber, Marjorie; Lichtvan, Leniza Costa Lima; Werner, Betina; Mehrdad Nadji, Mehrdad

    2017-01-01

    Congenital hemangiopericytoma (HPC) is a rare mesenchymal tumor with less aggressive behavior and a more favorable prognosis than similar tumors in adults. Multifocal presentation is even less common than isolated HPC and hence its clinical and histologic recognition may be challenging. A newborn infant with multifocal congenital HPC causing severe deformity but with a favorable outcome after chemotherapy and surgical removal is reported.

  3. Congenital heat disease

    SciTech Connect

    Higgins, C.B.; Silverman, N.H.; Kersting-Somerhoff, B.A.

    1990-01-01

    The book covers the tomographic anatomy of the normal and congenitally malformed heart and tomographic imaging of the normal heat. It then compares echocardiographic evaluation and the use of MR imaging in the diagnosis and evaluation of individual congenital cardiac malformations.

  4. Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia

    PubMed Central

    Royer-Bertrand, Beryl; Castillo-Taucher, Silvia; Moreno-Salinas, Rodrigo; Cho, Tae-Joon; Chae, Jong-Hee; Choi, Murim; Kim, Ok-Hwa; Dikoglu, Esra; Campos-Xavier, Belinda; Girardi, Enrico; Superti-Furga, Giulio; Bonafé, Luisa; Rivolta, Carlo; Unger, Sheila; Superti-Furga, Andrea

    2015-01-01

    We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of “mitochondrial chaperonopathies” and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis. PMID:26598328

  5. Abdominal vascular syndromes: characteristic imaging findings.

    PubMed

    Cardarelli-Leite, Leandro; Velloni, Fernanda Garozzo; Salvadori, Priscila Silveira; Lemos, Marcelo Delboni; D'Ippolito, Giuseppe

    2016-01-01

    Abdominal vascular syndromes are rare diseases. Although such syndromes vary widely in terms of symptoms and etiologies, certain imaging findings are characteristic. Depending on their etiology, they can be categorized as congenital-including blue rubber bleb nevus syndrome, Klippel-Trenaunay syndrome, and hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)-or compressive-including "nutcracker" syndrome, median arcuate ligament syndrome, Cockett syndrome (also known as May-Thurner syndrome), and superior mesenteric artery syndrome. In this article, we aimed to illustrate imaging findings that are characteristic of these syndromes, through studies conducted at our institution, as well as to perform a brief review of the literature on this topic.

  6. Down Syndrome: A Cardiovascular Perspective

    ERIC Educational Resources Information Center

    Vis, J. C.; Duffels, M. G. J.; Winter, M. M.; Weijerman, M. E.; Cobben, J. M.; Huisman, S. A.; Mulder, B. J. M.

    2009-01-01

    This review focuses on the heart and vascular system in patients with Down syndrome. A clear knowledge on the wide spectrum of various abnormalities associated with this syndrome is essential for skillful management of cardiac problems in patients with Down syndrome. Epidemiology of congenital heart defects, cardiovascular aspects and…

  7. Urinary Peptides in Rett Syndrome.

    ERIC Educational Resources Information Center

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  8. Mental retardation in a boy with congenital adrenal hypoplasia: a clue to contiguous gene syndrome involving DAX1 and IL1RAPL.

    PubMed

    Sasaki, Rie; Inamo, Yasuji; Saitoh, Kazumasa; Hasegawa, Tomonobu; Kinoshita, Eiichi; Ogata, Tsutomu

    2003-06-01

    We report on a 2 years and 9 months old Japanese boy with adrenal hypoplasia and mental retardation (MR) (developmental quotient approximately 60) which occurred in the absence of severe adrenal crisis and resultant brain damage. Cytogenetic and molecular studies were performed in this boy and his parents with normal phenotype, showing that the boy had a maternally derived approximately 2 Mb interstitial Xp deletion involving DAX1 (DSS-AHC critical region on the X chromosome, gene 1) for adrenal hypoplasia congenita and disrupting IL1RAPL (interleukin-1 receptor accessory protein-like) for non-specific MR. The results explain the development of MR in this boy in terms of contiguous gene syndrome, and suggest the importance of IL1RAPL analysis in patients with adrenal hypoplasia and MR.

  9. Use of an administrative database to determine clinical management and outcomes in congenital heart disease.

    PubMed

    Gutgesell, Howard P; Hillman, Diane G; McHugh, Kimberly E; Dean, Peter; Matherne, G Paul

    2011-10-01

    We review our 16-year experience using the large, multi-institutional database of the University HealthSystem Consortium to study management and outcomes in congenital heart surgery for hypoplastic left heart syndrome, transposition of the great arteries, and neonatal coarctation. The advantages, limitations, and use of administrative databases by others to study congenital heart surgery are reviewed.

  10. Giant congenital melanocytic nevus*

    PubMed Central

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion. PMID:24474093

  11. Giant congenital melanocytic nevus.

    PubMed

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion.

  12. Prevalence of congenital anomalies in newborns with congenital heart disease diagnosis

    PubMed Central

    Egbe, Alexander; Lee, Simon; Ho, Deborah; Uppu, Santosh; Srivastava, Shubhika

    2014-01-01

    Background: There is a known association between congenital heart disease (CHD) and other congenital anomalies (CA). These associations have been altered by changes in prenatal factors in recent time. We reviewed the largest database of inpatient hospitalization information and analyzed the current association between common CHD diagnoses and other congenital anomalies. Materials and Methods: Case-control study design. We reviewed the Nationwide Inpatient Sample (NIS) database from 1998 to 2008 and identified all live births with CHD diagnosis (case) and live births without CHD diagnosis (control). We compared prevalence of associated congenital anomalies between the case and control groups. Results: Our cohort consisted of 97,154 and 12,078,482 subjects in the case and control groups, respectively. In the CHD population, prevalence of non-syndromic congenital anomaly (NSCA), genetic syndrome (GS), and overall extra-cardiac congenital anomaly (CA) were 11.4, 2.2, and 13.6%, respectively. In the control group, prevalence of NSCA, GS, and CA were 6.7, 0.3, and 7.0%, respectively. NSCA (odds ratio (OR): 1.88, confidence interval (CI): 1.73-1.94), GS (OR 2.52, CI 2.44-2.61), and overall CA (OR: 2.01, CI: 1.97-2.14) were strongly associated with CHD. Prevalence of GS and multiple organ-system CA decreased significantly over the study period. Conclusions: This is the largest and most comprehensive population-based study evaluating association between CHD and extra-cardiac malformation (ECM) in newborns. There was significant decrease in prevalence of GS and multiple CA over the study period. PMID:24987252

  13. Hypoplastic left heart syndrome (image)

    MedlinePlus

    Hypoplastic left heart syndrome is a congenital heart condition that occurs during the development of the heart in the ... womb. During the heart's development, parts of the left side of the heart (mitral valve, left ventricle ...

  14. Genetics Home Reference: Lowe syndrome

    MedlinePlus

    ... named? Additional Information & Resources MedlinePlus (5 links) Encyclopedia: Congenital Cataract Encyclopedia: Fanconi Syndrome Health Topic: Developmental Disabilities Health Topic: Eye Diseases Health Topic: Kidney Diseases Genetic and Rare Diseases Information Center (1 link) ...

  15. Genetics Home Reference: Kleefstra syndrome

    MedlinePlus

    ... individuals may have a high birth weight and childhood obesity. People with Kleefstra syndrome may also have structural brain abnormalities, congenital heart defects, genitourinary abnormalities, seizures, ... During childhood they may exhibit features of autism or related ...

  16. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

    PubMed

    Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

    2015-07-01

    The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

  17. Giant congenital nevus

    MedlinePlus

    ... A congenital pigmented or melanocytic nevus is a dark-colored, often hairy, patch of skin. It is ... rare. Symptoms A nevus will appear as a dark-colored patch with any of the following: Brown ...

  18. Congenital complete heart block.

    PubMed Central

    Agarwala, B.; Sheikh, Z.; Cibils, L. A.

    1996-01-01

    Congenital complete heart block in utero has become diagnosed more frequently with the clinical use of fetal echocardiography. The fetus with complete heart block may remain asymptomatic or may develop congestive heart failure. Congenital complete heart block is more frequently seen in infants of mothers with systemic lupus erythematosus, both clinically manifested and subclinical systemic lupus erythematosus with positive antibodies (SS-A and SS-B antibodies). At birth, the neonate with complete heart block may remain asymptomatic and may not require a pacemaker to increase the heart rate. The indications for a pacemaker in neonates with complete heart block have been discussed. Both in-utero and neonatal management of congenital complete heart block are discussed to manage congestive heart failure in a fetus. Four patients with congenital complete heart block are presented covering a broad spectrum of clinical presentation, diagnosis, and management both in the fetal and neonatal period. Images Figure 1 PMID:8961692

  19. Congenital Heart Information Network

    MedlinePlus

    ... Baemayr for The Congenital Heart Information Network Exempt organization under Section 501(c)3. Copyright ©1996 - 2016 C.H.I.N. All rights reserved TX4-390-685 Original site design and HTML by Panoptic Communications

  20. Virus-induced congenital malformations in cattle.

    PubMed

    Agerholm, Jørgen S; Hewicker-Trautwein, Marion; Peperkamp, Klaas; Windsor, Peter A

    2015-09-24

    Diagnosing the cause of bovine congenital malformations (BCMs) is challenging for bovine veterinary practitioners and laboratory diagnosticians as many known as well as a large number of not-yet reported syndromes exist. Foetal infection with certain viruses, including bovine virus diarrhea virus (BVDV), Schmallenberg virus (SBV), blue tongue virus (BTV), Akabane virus (AKAV), or Aino virus (AV), is associated with a range of congenital malformations. It is tempting for veterinary practitioners to diagnose such infections based only on the morphology of the defective offspring. However, diagnosing a virus as a cause of BCMs usually requires laboratory examination and even in such cases, interpretation of findings may be challenging due to lack of experience regarding genetic defects causing similar lesions, even in cases where virus or congenital antibodies are present. Intrauterine infection of the foetus during the susceptible periods of development, i.e. around gestation days 60-180, by BVDV, SBV, BTV, AKAV and AV may cause malformations in the central nervous system, especially in the brain. Brain lesions typically consist of hydranencephaly, porencephaly, hydrocephalus and cerebellar hypoplasia, which in case of SBV, AKAV and AV infections may be associated by malformation of the axial and appendicular skeleton, e.g. arthrogryposis multiplex congenita. Doming of the calvarium is present in some, but not all, cases. None of these lesions are pathognomonic so diagnosing a viral cause based on gross lesions is uncertain. Several genetic defects share morphology with virus induced congenital malformations, so expert advice should be sought when BCMs are encountered.

  1. Genetics of Nonsyndromic Congenital Hearing Loss

    PubMed Central

    Egilmez, Oguz Kadir; Kalcioglu, M. Tayyar

    2016-01-01

    Congenital hearing impairment affects nearly 1 in every 1000 live births and is the most frequent birth defect in developed societies. Hereditary types of hearing loss account for more than 50% of all congenital sensorineural hearing loss cases and are caused by genetic mutations. HL can be either nonsyndromic, which is restricted to the inner ear, or syndromic, a part of multiple anomalies affecting the body. Nonsyndromic HL can be categorised by mode of inheritance, such as autosomal dominant (called DFNA), autosomal recessive (DFNB), mitochondrial, and X-linked (DFN). To date, 125 deafness loci have been reported in the literature: 58 DFNA loci, 63 DFNB loci, and 4 X-linked loci. Mutations in genes that control the adhesion of hair cells, intracellular transport, neurotransmitter release, ionic hemeostasis, and cytoskeleton of hair cells can lead to malfunctions of the cochlea and inner ear. In recent years, with the increase in studies about genes involved in congenital hearing loss, genetic counselling and treatment options have emerged and increased in availability. This paper presents an overview of the currently known genes associated with nonsyndromic congenital hearing loss and mutations in the inner ear. PMID:26989561

  2. Congenital anomalies of kidney and urinary tract.

    PubMed

    Toka, Hakan R; Toka, Okan; Hariri, Ali; Nguyen, Hiep T

    2010-07-01

    Congenital anomalies of the kidney and urinary tract anatomy (CAKUT) are common in children and represent approximately 30% of all prenatally diagnosed malformations. CAKUT is phenotypically variable and can affect the kidney(s) alone and/or the lower urinary tract. The spectrum includes more common anomalies such as vesicoureteral reflux and, rarely, more severe malformations such as bilateral renal agenesis. In young children, congenital anomalies are the leading cause of kidney failure and for kidney transplantation or dialysis. CAKUT can also lead to significant renal problems in adulthood and may present itself with hypertension and/or proteinuria. Congenital renal anomalies can be sporadic or familial, syndromic (also affecting nonrenal or non-urinary tract tissues), or nonsyndromic. Genetic causes have been identified for the syndromic forms and have shed some light into the molecular mechanisms of kidney development in human beings. The genetic causes for the more common nonsyndromic forms of CAKUT are unknown. The role of prenatal interventions and postnatal therapies as well as the benefits of screening affected individuals and their family members are not clear.

  3. Heart transplantation in adults with congenital heart disease.

    PubMed

    Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien

    2017-02-22

    With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes.

  4. Congenital hemophagocytic lymphohistiocytosis presenting as thrombocytopenia in a newborn.

    PubMed

    Hinson, Ashley; Owen, William; Prose, Neil; Parikh, Suhag; Thornburg, Courtney

    2015-05-01

    Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by dysregulation and hyperactivation of the immune system, and can be familial or acquired. HLH presenting in infancy can be rapidly fatal if not promptly recognized and treated. Congenital HLH can be caused by various genetic mutations or part of immunodeficiency syndromes. We present an infant with Griscelli syndrome and familial HLH with atypical genetic mutations, presenting as thrombocytopenia on the first day of life, cured with chemotherapy and unrelated cord blood transplant.

  5. Rare association of anophthalmia, complex congenital heart disease and pulmonary hypertension: case report.

    PubMed

    Ríos-Méndez, Raúl Enrique; Lozano Chinga, Michell Marola

    2016-10-07

    Clinical congenital anophthalmia is described as the uni- or bilateral absence of the eyeball that might occur in isolation or as part of a syndrome. It has a very low prevalence and its etiology is heterogeneous. Complex congenital cardiac malformations are also rare. The association of congenital anophthalmia and congenital heart disease is rarer still, and the etiology of those associations is not well understood yet. We report the case of a patient who had the very rare association of bilateral anophthalmia, multiple cardiac malformations and severe pulmonary hypertension.

  6. Pallister-Killian syndrome.

    PubMed

    Izumi, Kosuke; Krantz, Ian D

    2014-12-01

    Pallister-Killian syndrome (PKS) is characterized by craniofacial dysmorphism, pigmentary skin anomalies, congenital heart defects, congenital diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. PKS is caused by extra copies of chromosome 12p, most characteristically a marker isochromosome 12p that demonstrates tissue-limited mosaicism. The cytogenetic diagnosis of PKS is often cumbersome due to the absence of the isochromosome in lymphocytes requiring sampling of other tissues. The mechanism by which the isochromosome 12p results in the constellation of multiple congenital anomalies remains largely unknown. In this review, we summarize the background of, and recent advances in, the clinical and molecular understanding of PKS.

  7. Limb-threatening ischemia secondary to a congenital acromioclavicular remnant.

    PubMed

    Enlow, Jonathan M; McGregor, Walter E

    2009-07-01

    Upper extremity vascular compromise from thoracic outlet syndrome is rare and is usually the result of a "cervical rib," anterior scalene muscle abnormality, or clavicular trauma. We report a case of acute axillary artery thrombosis secondary to a congenital acromioclavicular remnant in a 40-year-old woman.

  8. Congenital bilateral syngnathia and tracheoesophageal fistula: A rare presentation

    PubMed Central

    Khasgiwala, Ankit; Jangam, Sagar; Sharma, Shashi; Newaskar, Vilas

    2016-01-01

    Congenital syngnathia (CS), first reported by Burket in 1936, is a rare condition, with <50 reported cases and is associated with other conditions and syndromes. CS restricts mouth opening, causing difficulty in feeding, swallowing, and respiration. This report puts forth the clinical findings and management of this challenging condition in association with tracheoesophageal fistula in a neonate. PMID:27994431

  9. Pulmonary arterial hypertension in congenital heart diseases.

    PubMed

    Beghetti, Maurice; Tissot, Cecile

    2009-08-01

    Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.

  10. Neurophysiological Strategies for the Diagnosis of Disorders of the Neuromuscular Junction in Children

    ERIC Educational Resources Information Center

    Pitt, Matthew

    2008-01-01

    The disorders of the neuromuscular junction seen in children, the congenital myasthenic syndromes and autoimmune myasthenia gravis, are very rare. Their clinical symptoms and signs may be variable, most notably in the neonate and infant. They should enter the differential diagnosis of many different clinical presentations, such as "floppy infant"…

  11. The Nager acrofacial dysostosis syndrome with the tetralogy of Fallot.

    PubMed

    Thompson, E; Cadbury, R; Baraitser, M

    1985-10-01

    A male infant is described with mandibulofacial dysostosis and absent thumbs, consistent with the Nager acrofacial dysostosis syndrome. In addition, the tetralogy of Fallot was present. Major congenital heart malformations occur rarely in this syndrome.

  12. Genetics of Congenital Cataract.

    PubMed

    Pichi, Francesco; Lembo, Andrea; Serafino, Massimiliano; Nucci, Paolo

    2016-01-01

    Congenital cataract is a type of cataract that presents at birth or during early childhood, and it is one of the most easily treatable causes of visual impairment and blindness during infancy, with an estimated prevalence of 1-6 cases per 10,000 live births. Approximately 50% of all congenital cataract cases may have a genetic cause, and such cases are quite heterogeneous. Although congenital nuclear cataract can be caused by multiple factors, genetic mutation remains the most common cause. All three types of Mendelian inheritance have been reported for cataract; however, autosomal dominant transmission seems to be the most frequent. The transparency and high refractive index of the lens are achieved by the precise architecture of fiber cells and homeostasis of the lens proteins in terms of their concentrations, stabilities, and supramolecular organization. Research on hereditary congenital cataract has led to the identification of several classes of candidate genes that encode proteins such crystallins, lens-specific connexins, aquaporin, cytoskeletal structural proteins, and developmental regulators. In this review, we highlight the identified genetic mutations that account for congenital nuclear cataract.

  13. What Are Congenital Heart Defects?

    MedlinePlus

    ... heart disease. Google+ Hangout on the first large-scale gene sequencing analysis of congenital heart disease 05/ ... in the journal Nature, about the first large-scale sequencing analysis of congenital heart disease. This NHLBI- ...

  14. Types of Congenital Heart Defects

    MedlinePlus

    ... heart disease. Google+ Hangout on the first large-scale gene sequencing analysis of congenital heart disease 05/ ... in the journal Nature, about the first large-scale sequencing analysis of congenital heart disease. This NHLBI- ...

  15. Environmental aspects of congenital scoliosis.

    PubMed

    Li, Zheng; Yu, Xin; Shen, Jianxiong

    2015-04-01

    Growing evidence has proved that many aspects of our lifestyle and the environment contribute to the development of congenital disease. Congenital spinal deformities are due to anomalous development of the vertebrae including failure of formation and segmentation during embryogenesis. The causes of congenital scoliosis have not been fully identified. A variety of factors are implicated in the development of vertebral abnormalities. Previous studies have demonstrated that both genetics and environmental factors are implicated in the development of vertebral abnormalities. However, no specific cause for congenital scoliosis has been identified. In our review, we focus on the environmental factors for the development of congenital scoliosis. Various maternal exposures during pregnancy including hypoxia, alcohol use, vitamin deficiency, valproic acid, boric acid, and hyperthermia have been observed to be associated with the occurrence of congenital scoliosis. This review describes the major environmental contributors of congenital scoliosis with an emphasis on treatment aspects associated with environmental disposition in congenital scoliosis.

  16. Genetics Home Reference: congenital hyperinsulinism

    MedlinePlus

    ... of infancy Great Ormond Street Hospital for Children (UK) Merck Manual Consumer Version: Hypoglycemia Orphanet: Congenital isolated ... Diseases Congenital Hyperinsulinism International The Children's Hyperinsulinism Fund (UK) GeneReviews (1 link) Familial Hyperinsulinism ClinicalTrials.gov (1 ...

  17. The Importance of Nomenclature for Congenital Heart Disease: Implications for Research and Evaluation

    PubMed Central

    Strickland, Matthew J; Riehle-Colarusso, Tiffany J; Jacobs, Jeffrey P; Reller, Mark D; Mahle, William T; Botto, Lorenzo D; Tolbert, Paige E; Jacobs, Marshall L; Lacour-Gayet, Francois G; Tchervenkov, Christo I; Mavroudis, Constantine; Correa, Adolfo

    2013-01-01

    Background Administrative databases are often used for congenital heart disease research and evaluation, with little validation of the accuracy of the diagnostic codes. Methods Metropolitan Atlanta Congenital Defects Program surveillance records were reviewed and classified using a version of the International Pediatric and Congenital Cardiac Code. Using this clinical nomenclature as the referent, we report the sensitivity and false positive fraction (1 – positive predictive value) of the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for tetralogy of Fallot, transposition of the great arteries, and hypoplastic left heart syndrome. Results We identified 4918 infants and foetuses with congenital heart disease from the surveillance records. Using only the International Classification of Diseases diagnosis codes, there were 280 records with tetralogy, 317 records with transposition, and 192 records with hypoplastic left heart syndrome. Based on the International Pediatric and Congenital Cardiac Code, 330 records were classified as tetralogy, 163 records as transposition, and 179 records as hypoplastic left heart syndrome. The sensitivity of International Classification of Diseases diagnosis codes was 83% for tetralogy, 100% for transposition, and 95% for hypoplastic left heart syndrome. The false positive fraction was 2% for tetralogy, 49% for transposition, and 11% for hypoplastic left heart syndrome. Conclusions Analyses based on International Classification of Diseases diagnosis codes may have substantial misclassification of congenital heart disease. Isolating the major defect is difficult, and certain codes do not differentiate between variants that are clinically and developmentally different. PMID:19063779

  18. The epidemiology and prevention of congenital cytomegalovirus infection and disease: activities of the Centers for Disease Control and Prevention Workgroup.

    PubMed

    Ross, Danielle S; Dollard, Sheila C; Victor, Marcia; Sumartojo, Esther; Cannon, Michael J

    2006-04-01

    Perhaps no single cause of birth defects and developmental disabilities in the United States currently provides greater opportunity for improved outcomes in more children than congenital cytomegalovirus (CMV). --Cannon and Davis. BMC Public Health 2005;5:70 Each year in the United States, thousands of children and their families are affected by congenital cytomegalovirus (CMV) infection. More children may be affected by congenital CMV than by other, better known childhood conditions, such as Down syndrome, fetal alcohol syndrome, and spina bifida. The Centers for Disease Control and Prevention (CDC) has formed a Workgroup on Congenital CMV, led by the National Center on Birth Defects and Developmental Disabilities and the National Center on Infectious Diseases. This report provides background on congenital CMV infection and describes the goals and activities of the workgroup for reducing the burden of sequelae of congenital CMV infection.

  19. Leber's congenital amaurosis.

    PubMed

    Mizuno, K; Takei, Y; Sears, M L; Peterson, W S; Carr, R E; Jampol, L M

    1977-01-01

    An early stage of Leber's congenital amaurosis, characterized by white spots or lines in the fundus, occurred in two children. Light microscopic examination of eyes obtained from one child, a 16-month-old Japanese girl, revealed subretinal deposits corresponding to the white spots and lines in the fundus deposits. Light and electron microscopic examination of the eye showed distinctive changes in the outer retinal layers and choroid, while the inner retinal layers were nearly normal. Characteristic early lesions of congenital amaurosis appeared to be produced by deposits consisting of loose outer segments and apical processes of the pigmental epithelial cell and macrophages. Undifferentiation in the nuclei of the photoreceptor cell, the inner segment, the pigment epithelial cell, and the choriocapillaris were likely characteristics of the early changes of congenital amaurosis.

  20. Pallister-Killian syndrome: report of one case.

    PubMed

    Wu, Hui-Chung; Lin, Lung-Huang; Tsai, Li-Ping; Huang, Cheng-Hung; Hung, Kun-Long; Liao, Hung-Tsai

    2006-01-01

    Pallister-Killian Syndrome (PKS) is a rare sporadic congenital anomaly disorder, characterized by multiple congenital anomalies, especially craniofacial dysmorphism. It is also associated with mental retardation, seizure, skin pigmentation, and visceral malformations such as congenital diaphragmatic hernia, congenital heart defect, anorectal anomalies, and genital malformation. This syndrome usually presents with tissue-limited mosaicism of supernumerary 12p isochromosome i (12p). Moreover, diagnosis of Pallister-Killian Syndrome (PKS) is difficult because the ratio of abnormal to normal karyotyping is much lower in peripheral lymphocytes than in skin fibroblasts. We report the first case in Taiwan, who has tetrasomy 12p mosaic in peripheral lymphocytes.

  1. Congenital Muscle Disease Study of Patient and Family Reported Medical Information

    ClinicalTrials.gov

    2017-01-30

    Muscular Dystrophy; Congenital Muscular Dystrophy; Fukutin-related Protein Gene; Limb Girdle; FKRP Gene; Childhood Onset LGMD; Adult Onset LGMD; POMT1; POMT2; POMGnT1; LARGE; Alpha Dystroglycan; Dystroglycanopathy; Centronuclear; Multiminicore; Multicore; Minicore; Congenital Fiber Type Disproportion; Myotubular; Nemaline; Congenital Myopathy; Neuromuscular; Rigid Spine; Phenotype-Genotype Correlation; Cough Assisted Device; Neuromuscular Disease; Respiratory Exacerbation; Invasive Ventilation; Chest Physiotherapy; Congenital Myopathies; Genetic Mutations; Hypertrophic Cardiomyopathy; Wheelchair Use; Cataract; Opthalmoplegia; Ullrich Congenital Muscular Dystrophy; Intermediate Collagen VI Myopathy; Laminin Alpha 2 Related Congenital Muscular Dystrophy; MDC1A; Merosin Deficient Congenital Muscular Dystrophy; Congenital Muscular Dystrophy Undiagnosed; Congenital Muscular Dystrophy Merosin Positive; Walker Warburg Syndrome; Muscle Eye Brain Disease; Fukuyama; Integrin Alpha 7 Deficiency; Integrin Alpha 9 Deficiency; Laminopathy; Lamin AC; SEPN1 Related Myopathies; Bethlem Myopathy; Dystroglycanopathies; LGMD2K; LGMD2I; LGMD2L; LGMD2N; Actin Aggregation Myopathy; Cap Disease; Central Core Disease; Centronuclear Myopathy; Core Rod Myopathy; Hyaline Body Myopathy; Multiminicore Myopathy; Myotubular Myopathy; Nemaline Myopathy; Tubular Aggregate Myopathy; Zebra Body Disease Myopathy; Congenital Myopathy Other; Reducing Body Myopathy; Sarcotubular Myopathy; Spheroid Body Myopathy

  2. Congenital Hemolytic Anemia.

    PubMed

    Haley, Kristina

    2017-03-01

    Red blood cell (RBC) destruction can be secondary to intrinsic disorders of the RBC or to extrinsic causes. In the congenital hemolytic anemias, intrinsic RBC enzyme, RBC membrane, and hemoglobin disorders result in hemolysis. The typical clinical presentation is a patient with pallor, anemia, jaundice, and often splenomegaly. The laboratory features include anemia, hyperbilirubinemia, and reticulocytosis. For some congenital hemolytic anemias, splenectomy is curative. However, in other diseases, avoidance of drugs and toxins is the best therapy. Supportive care with transfusions are also mainstays of therapy. Chronic hemolysis often results in the formation of gallstones, and cholecystectomy is often indicated.

  3. Congenital brain infections.

    PubMed

    Arbelaez, Andres; Restrepo, Feliza; Davila, Jorge; Castillo, Mauricio

    2014-06-01

    Pediatric congenital intracranial infections are a group of different and important entities that constitute a small percentage of all pediatric infections. The causal factors and clinical presentations are different in children compared with adults. They require early recognition because delay diagnosis and initiation of treatment may have catastrophic consequences. Despite improvements in prenatal screening, vaccine safety, and antibiotics, infections of the central nervous system remain an important cause of neurological disabilities worldwide. This article reviews the most common congenital infections and their imaging findings.

  4. Congenital Adrenal Hyperplasia

    PubMed Central

    Speiser, Phyllis W.

    2015-01-01

    Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management. PMID:26339484

  5. Congenital Toxoplasmosis: A Review.

    PubMed

    Hampton, Marissa Martinez

    2015-01-01

    Acute infection of toxoplasmosis during pregnancy is detrimental to the developing fetus. In the United States, approximately 1 in 10,000 live births are affected by congenital toxoplasmosis. Although multifactorial in etiology, maternal infection is primarily attributed to the consumption of contaminated meat or water. Infection and transmission to the fetus may result in devastating neurologic impairment. Screening methods for all pregnant women should be implemented in routine prenatal care. This article will highlight the inherent dangers of congenital toxoplasmosis, while including general care of the fetus for prevention of transmission, medical management, and long-term outcomes.

  6. West syndrome in a patient with Schinzel-Giedion syndrome.

    PubMed

    Miyake, Fuyu; Kuroda, Yukiko; Naruto, Takuya; Ohashi, Ikuko; Takano, Kyoko; Kurosawa, Kenji

    2015-06-01

    Schinzel-Giedion syndrome is a rare recognizable malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. The causative gene of Schinzel-Giedion syndrome, SETBP1, has been identified, but limited cases have been confirmed by molecular analysis. We present a 9-month-old girl affected by West syndrome with Schinzel-Giedion syndrome. Congenital severe hydronephrosis, typical facial features, and multiple anomalies suggested a clinical diagnosis of Schinzel-Giedion syndrome. Hypsarrhythmia occurred at 7 months of age and was temporarily controlled by adrenocorticotropic hormone (ACTH) therapy during 5 weeks. SETBP1 mutational analysis showed the presence of a recurrent mutation, p.Ile871Thr. The implications in management of Schinzel-Giedion syndrome are discussed.

  7. A new case of Okamoto syndrome.

    PubMed

    Wallerstein, Robert; Shih, Ling-yu; Fong, Mei-Heung; Zheng, Sharon; Poon, Eric

    2005-04-01

    We report a 6 month old boy with congenital hydronephrosis, cleft palate, severe hypotonia, congenital heart defect, developmental delay, and characteristic facial features with an open mouthed appearance and full lower lip, who we believe is the third reported case of Okamoto syndrome. Okamoto syndrome is a recently described distinctive multiple congenital anomaly syndrome encompassing the above features for which an etiologic factor has not yet been identified. Our patient also had idiopathic splenomegaly and non-specific MRI changes in the brain, not reported in the first two cases.

  8. [Congenital gastrointestinal diseases with manifestations in adulthood].

    PubMed

    Rösch, W

    1977-02-03

    A genetic background is discussed in many disorders of the gastrointestinal tract with a disposition in addition to environmental factors. The pathophysiology of most hereditary diseases is unknown although the mode of inheritance is established. Biochemical analysis may show molecular defects or inborn lack of enzymes, cytogenetic studies may reveal chromosomal abnormalities. The knowledge of genetic factors in gastrointestinal disorders may contribute to the early detection of persons afflicted but not yet symptomatic, in some rare syndromes genetic counseling may become mandatory. Finally, there are many congenital malformations which may not cause symptoms for many years so that doubts may arise whether they are developmental anomalies or acquired conditions.

  9. Reconstruction of congenital defects of the vagina.

    PubMed

    Eldor, Liron; Friedman, Jeffrey D

    2011-05-01

    Congenital absence of the vagina is a relatively rare condition most commonly associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Historically, several reconstructive techniques have been described to provide for functional vaginal reconstruction on these patients, both operative and nonoperative. Although there are many advantages and disadvantages of the various procedures, one experience with the use of split thickness skin grafts to reconstruct the vagina has produced acceptable functional results with limited donor site morbidity. Careful planning and timing of this form of reconstruction can produce predictable results in patients who are nearing sexual maturity.

  10. Arthrogryposis Multiplex Congenita: Multiple Congenital Joint Contractures

    PubMed Central

    Sucuoglu, Hamza; Ornek, Nurettin Irem; Caglar, Cagkan

    2015-01-01

    Arthrogryposis multiplex congenita (AMC) is a syndrome characterized by nonprogressive multiple congenital joint contractures. The etiology of disease is multifactorial; it is most commonly suspected from absent fetal movements and genetic defects. AMC affects mainly limbs; also it might present with other organs involvement. It is crucial that the diagnosis of AMC should be kept in mind by musculoskeletal physicians in newborns with multiple joint contractures and patients must begin rehabilitation in early stage after accurate diagnosis in terms of functional independence. We present the diagnosis, types, clinical features, and treatment approaches of this disease in our case with literature reviews. PMID:26604929

  11. A novel Fryns "Anophthalmia-plus" syndrome associated with primary hypothyroidism.

    PubMed

    Akalin, I; Senses, D A; Ilgin-Ruhi, H; Misirlioğlu, E; Yalçiner, M; Cetinkaya, E; Fryns, J P; Tükün, A

    2005-01-01

    A novel Fryns "anophthalmla-plus" syndrome associated with primary hypothyroidism: Here, we report a newborn male with "anophthalmia-plus" syndrome and primary congenital hypothyroidism. To our knowledge this is the first case of 'anophthalmia-plus' syndrome associated with congenital hypothyroidism in the literature up to date.

  12. Sexuality and quality of life in congenital hypogonadisms.

    PubMed

    Garrido Oyarzún, María Fernanda; Castelo-Branco, Camil

    2016-12-01

    Turner syndrome and idiopathic congenital hypogonadism including Kallmann syndrome are conditions associated to a large number of widely known comorbidities that need a medical support forever. One of the characteristics shared by both conditions is the lack of sexual development that influencing the sexuality functioning and quality of life of the affected women. Few studies have been conducted to assess these topics, but they need to be considered in the treatment to all women with hypogonadism. This review on the major medical issues and psychological aspects, also focus in the present knowledge about sexual function and quality of life of women with Turner syndrome and idiopathic congenital hypogonadism, which aims to help in the comprehensive management of these patients.

  13. Hardikar syndrome: long term outcome of a rare genetic disorder.

    PubMed

    Nydegger, Andreas; Van Dyck, Maria; Fisher, Robert A; Jaeken, Jaak; Hardikar, Winita

    2008-10-01

    Hardikar syndrome is a rare disorder of unknown etiology. Features of the syndrome are manifold with a predominance of liver and renal involvement. The syndrome is clearly distinct from other previously described syndromes such as Alagille syndrome, congenital hepatic fibrosis, Caroli disease, and Kabuki make-up syndrome. To date, only four cases of Hardikar syndrome have been published worldwide. We report here on the long term outcome of these patients.

  14. Currarino syndrome and spinal dysraphism.

    PubMed

    Kole, Matthew J; Fridley, Jared S; Jea, Andrew; Bollo, Robert J

    2014-06-01

    Currarino syndrome is a rare constellation of congenital anomalies characterized by the triad of sacral dysgenesis, presacral mass, and anorectal malformation. It is frequently associated with other congenital anomalies, often including occult spinal dysraphism. Mutations in the MNX1 gene are identified in the majority of cases. The authors report a rare case of Currarino syndrome in an infant with tethered cord syndrome and a dorsal lipomyelomeningocele continuous with a presacral intradural spinal lipoma, in addition to an imperforate anus and a scimitar sacrum. They review the literature to highlight patterns of occult spinal dysraphism in patients with Currarino syndrome and their relationship to tethered cord syndrome. Approximately 60% of the patients with Currarino syndrome reported in the literature have an occult spinal dysraphism. Published studies suggest that the risk of tethered cord syndrome may be higher among patients with a lipoma and lower among those with a teratoma or anterior meningocele.

  15. Congenital heart disease and chromossomopathies detected by the karyotype

    PubMed Central

    Trevisan, Patrícia; Rosa, Rafael Fabiano M.; Koshiyama, Dayane Bohn; Zen, Tatiana Diehl; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo G.

    2014-01-01

    OBJECTIVE: To review the relationship between congenital heart defects and chromosomal abnormalities detected by the karyotype. DATA SOURCES: Scientific articles were searched in MEDLINE database, using the descriptors "karyotype" OR "chromosomal" OR "chromosome" AND "heart defects, congenital". The research was limited to articles published in English from 1980 on. DATA SYNTHESIS: Congenital heart disease is characterized by an etiologically heterogeneous and not well understood group of lesions. Several researchers have evaluated the presence of chromosomal abnormalities detected by the karyotype in patients with congenital heart disease. However, most of the articles were retrospective studies developed in Europe and only some of the studied patients had a karyotype exam. In this review, only one study was conducted in Latin America, in Brazil. It is known that chromosomal abnormalities are frequent, being present in about one in every ten patients with congenital heart disease. Among the karyotype alterations in these patients, the most important is the trisomy 21 (Down syndrome). These patients often have associated extra-cardiac malformations, with a higher risk of morbidity and mortality, which makes heart surgery even more risky. CONCLUSIONS: Despite all the progress made in recent decades in the field of cytogenetic, the karyotype remains an essential tool in order to evaluate patients with congenital heart disease. The detailed dysmorphological physical examination is of great importance to indicate the need of a karyotype. PMID:25119760

  16. A new syndrome: right-sided arcus aorta syndrome.

    PubMed

    Ozkaya, Sevket; Dirican, Adem; Tuna, Tibel; Ece, Ferah

    2013-09-12

    Right-sided arcus aorta (RSAA) is a rare congenital anomaly that may cause chronic cough and dyspnoea. We aimed to define RSAA as a new syndrome characterised by RSAA, dyspnoea and cough during exercise. RSAA syndrome should be included in the differential diagnosis of asthma.

  17. Adult Congenital Heart Association

    MedlinePlus

    ... my congenital heart … Read More Let's Talk About Love... BY Kelly DiMaggio Being in love and in a relationship is one of the ... are born they have … Read More Learning to Love the Scar BY Clare Almand I wrote about ...

  18. Congenital adrenal hyperplasia

    MedlinePlus

    ... or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to 18,000 ... penis but normal testes Well-developed muscles Both boys and girls will be tall as children, but much shorter ...

  19. Congenital knee dislocation in a 49,XXXXY boy.

    PubMed Central

    Sijmons, R H; van Essen, A J; Visser, J D; Iprenburg, M; Nelck, G F; Vos-Bender, M L; de Jong, B

    1995-01-01

    We report on a 12 year old mentally retarded boy who presented at birth with bilateral knee dislocations, dislocation of the right hip, and general joint laxity. Cytogenetic studies showed a 49,XXXXY karyotype. Hyperlaxity of joints is known to occur in 49,XXXXY patients, but congenital knee dislocation has not been reported. Rarely in 49,XXXXY and 49,XXXXX syndromes Larsen-like features may be seen. Patients with congenital joint dislocation or laxity, combined with other malformations, especially if psychomotor development is delayed, should be karyotyped to exclude chromosomal abnormalities. Images PMID:7643364

  20. Congenital cataracts and other abnormalities in a female with 46.X, del(X)(q26q28)mat: A new locus for X-linked congenital cataract?

    SciTech Connect

    Babul, R.; Chitayat, D.; Teshima, I.

    1994-09-01

    Three forms of X-linked congenital cataracts have been delineated: congenital cataract with posterior Y-sutural opacities in heterozygotes, congenital cataract and microcornea or microphthalmia and congenital cataract-dental syndrome (Nance-Horan syndrome). Of these, only the Nance-Horan syndrome has been mapped to Xp22.3-p21.1. However, Warburg has suggested that these different forms of X-linked congenital cataracts are due to deletions of varying sizes, placing them in the vicinity of the Nance-Horan syndrome region. We report on a female patient born to a 29-year-old primigravida woman who at birth was found to have hypotonia, dysmorphic facial features, hydrocephalus and dense white congenital bilateral cataracts. Other ophthalmological findings included bilateral nystagmus and shallow orbits. Chromosome analysis revealed 46,X,del(X)(q26q28)mat. The mother, however, is phenotypically normal. Brain CT scan on the female infant revealed communicating hydrocephalus and a muscle biopsy showed congenital muscle fiber disproportion. An EMG and NCV were normal. At 4 years of age, her height and weight were below -3SD and her OFC was +2SD. Molecular studies using DNA markers located in Xq26-qter have revealed that the proximal breakpoint in the patient and her mother is defined by the HPRT locus while the distal breakpoint is defined by the locus DXS1108. This indicates that the deletion is not terminal but rather interstitial, retaining sequences proximal to the telomeric region. Other molecular studies are in progress to determine the X-inactivation status of the deleted chromosome in our patient and her mother as a possible explanation for the variation in the phenotype. These clinical and molecular findings suggest that another locus for X-linked congenital cataract exists at Xq26-28.

  1. Apert's Syndrome

    PubMed Central

    Jyothsna, Mandapati; Ahmed, Syed Basheer; Sree Lakshmi, Ketham Reddy

    2014-01-01

    ABSTRACT Apert's syndrome (acrocephalosyndactyly) is a rare congenital disorder characterized by craniosynostosis, midfacial malforma­tion and symmetrical syndactyly of hands and feet. Craniofacial deformities include cone-shaped calvarium, fat forehead, prop-tosis, hypertelorism and short nose with a bulbous tip. Intraoral findings include high arched palate with pseudocleft, maxillary transverse and sagittal hypoplasia with concomitant dental crowding, skeletal and dental anterior open bite and several retained primary teeth. We report one such case of 14-year-old boy having all the classical features of Apert's syndrome with particular emphasis on brief review of genetic features. How to cite this article: Kumar GR, Jyothsna M, Ahmed SB, Lakshmi KRS. Apert's Syndrome. Int J Clin Pediatr Dent 2014;7(1):69-72. PMID:25206244

  2. Clinical presentation and management of congenital ptosis

    PubMed Central

    Marenco, Marco; Macchi, Ilaria; Macchi, Iacopo; Galassi, Emilio; Massaro-Giordano, Mina; Lambiase, Alessandro

    2017-01-01

    Congenital ptosis is a rare condition characterized by lower positioning of the upper eyelid that is present at birth and is a clinical condition that is persistent if not treated. It may be unilateral or bilateral and may be associated with other ocular disorders or systemic conditions, including Marcus Gunn, Horner, and Duane syndromes. It is a benign condition but causes functional, cosmetic, and psychological problems in children. However, not all patients need to undergo surgery, and usually only patients at risk of amblyopia need a prompt surgical correction, while in other cases, surgery can be postponed. The grade of ptosis, the eyelid function, and the amblyopic risk are the parameters that affect the ophthalmologist’s decision on timing of surgery and the surgical technique to be used. In fact, there are several types of surgical techniques to correct a congenital ptosis, although very often more than one is needed to obtain an acceptable result. This paper reviews the causes of congenital ptosis and associated diseases. Particular emphasis is given to surgical management and different procedures available to correct the upper eyelid anomaly and avoid permanent damage to visual function. PMID:28280295

  3. Radiographic findings of Proteus Syndrome.

    PubMed

    Gandhi, Nishant Mukesh; Davalos, Eric A; Varma, Rajeev K

    2014-01-01

    The extremely rare Proteus Syndrome is a hamartomatous congenital syndrome with substantial variability between clinical patient presentations. The diagnostic criteria consist of a multitude of clinical findings including hemihypertrophy, macrodactyly, epidermal nevi, subcutaneous hamartomatous tumors, and bony abnormalities. These clinical findings correlate with striking radiographic findings.

  4. Radiographic findings of Proteus Syndrome

    PubMed Central

    Gandhi, Nishant Mukesh; Davalos, Eric A.; Varma, Rajeev K.

    2015-01-01

    The extremely rare Proteus Syndrome is a hamartomatous congenital syndrome with substantial variability between clinical patient presentations. The diagnostic criteria consist of a multitude of clinical findings including hemihypertrophy, macrodactyly, epidermal nevi, subcutaneous hamartomatous tumors, and bony abnormalities. These clinical findings correlate with striking radiographic findings. PMID:27186241

  5. Seminar on Usher's Syndrome: Proceedings.

    ERIC Educational Resources Information Center

    Rochester School for the Deaf, NY.

    Summarized are the presentation of M. Vernon and the Comments of primary panelists from a seminar on Usher's Syndrome, a genetic disease involving congenital deafness and progressive loss of vision due to retinitis pigmentosa. The following topics are addressed: genetics today, nature of Usher's Syndrome, symptoms, prevalence, lay diagnosis for…

  6. Congenital basilar impression: correlated neurological syndromes.

    PubMed

    Bassi, P; Corona, C; Contri, P; Paiocchi, A; Loiero, M; Mangoni, A

    1992-01-01

    A series of 8 cases operated on for symptomatic basilar impression associated with occipitalization of the atlas is reported (with or without atlantoaxial dislocation). Symptoms of onset (such as the frequent association between nuchal pain and vertigo) are emphasized and analyzed in relation to the pathogenetic mechanism that underlies the multiform symptomatology of the basilar impression. The diagnostic workup for basilar impression foresees X-rays, magnetic resonance imaging and computed tomography. The most important diagnostic problem is that of considering the possible existence of such a pathology in the presence of very common symptoms such as nuchal pain and vertigo. The surgical treatment has certainly been useful both to improve and to stabilize the symptomatology mainly when there is atlantoaxial dislocation. In fact in these cases the symptomatology is more severe and progressive for the alteration of the transverse ligament of the atlas secondary to abnormal mechanical stimuli.

  7. The Usher's Syndrome Adolescent: Programming Implications for School Administrators, Teachers, and Residential Advisors.

    ERIC Educational Resources Information Center

    Hicks, Wanda M.; Hicks, Doin E.

    1981-01-01

    The article examines educational programing implications for adolescents with Usher's syndrome, a condition of congenital deafness accompanied by progressive loss of vision through retinitis pigmentosa. (DB)

  8. Young-Simpson syndrome (YSS), a variant of del(1)(p36) syndrome?

    PubMed

    Robinson, Deanne Mraz; Meagher, Cecilia C; Orlowski, Craig C; Lagoe, Erin Caine; Fong, Chin-To

    2008-06-15

    The Young-Simpson syndrome (YSS) and 1p36 deletion syndrome are both characterized by facial and heart abnormalities, congenital hypothyroidism, and severe growth and developmental retardation. However, the YSS is characterized by the presence of blepharophimosis and epicanthus inversus, findings not described in monosomy 1p36 patients. We describe a girl with YSS, who presented with the typical facial findings, global retardation, congenital hypothyroidism, and congenital dilated cardiomyopathy. Comparative genomic hybridization chromosomal microarray analysis showed a 1p36.3 deletion, a finding not previously reported in other YSS cases. We propose that YSS is a variant of the 1p36 deletion syndrome.

  9. Genetic diagnosis for congenital hemolytic anemia.

    PubMed

    Ohga, Shouichi

    Congenital hemolytic anemia is a group of monogenic diseases presenting with anemia due to increased destruction of circulating erythrocytes. The etiology of inherited anemia accounts for germline mutations of the responsible genes coding for the structural components of erythrocytes and extra-erythrocytes. The erythrocyte abnormalities are classified into three major disorders of red cell membrane defects, hemoglobinopathies, and red cell enzymopathies. The extra-erythrocyte abnormalities, typified by consumption coagulopathy and intravascular hemolysis, include Upshaw-Schulman syndrome and atypical hemolytic uremic syndrome. The clinical manifestations of congenital hemolytic anemia are anemia, jaundice, cholelithiasis and splenomegaly, while the onset mode and severity are both variable. Genetic overlapping of red cell membrane protein disorders, and distinct frequency and mutation spectra differing among races make it difficult to understand this disease entity. On the other hand, genetic modifiers for the phenotype of β-globin diseases provide useful information for selecting the optimal treatment and for long-term management. Recently, next generation sequencing techniques have enabled us to determine the novel causative genes in patients with undiagnosed hemolytic anemias. We herein review the concept and strategy for genetic diagnosis of inherited hemolytic anemias.

  10. Iris mammillations in two female siblings with congenital adrenal hyperplasia.

    PubMed

    Peyman, Mohammadreza; Ong, Ming Jew; Iqbal, Tajunisah; Subrayan, Visvaraja

    2010-12-29

    Iris mammillations are dark brown, smooth, mound- or dome-shaped protuberances that are typically found on the anterior iris surface and are presumed to be congenital in origin. This congenital anomaly is usually unilateral and can be hereditary or sporadic. Lisch nodules in neurofibromatosis, tapioca melanoma of the iris, inflammatory iris granulomata and Cogan-Reese syndrome should be considered in the differential diagnosis. In this case report, the authors present a case of a bilateral iris mammillations in two siblings with congenital adrenal hyperplasia (CAH). To our knowledge, this is the first case where bilateral iris mammilations have been found to be associated with a systemic condition. Iris mammillations can be considered as one of the clinical signs in CAH in view of the pathogenesis discussed. Detailed ocular examination in CAH may reveal an increased incidence.

  11. The association of congenital spinal anomalies with imperforate anus.

    PubMed

    Denton, J R

    1982-01-01

    Ninety-four patients with congenital imperforate anus were studied to investigate: (1) the incidence of congenital spinal anomalies; (2) the orthopedic significance of these anomalies; (3) the incidence of other musculoskeletal disorders; and (4) the incidence of anomalies in other organ systems in the anal-spine anomaly group. There was a 38% incidence of spinal anomalies in 94 patients with congenital imperforate anus. Most of these abnormalities were sacral, and there were no related or progressive spinal deformities. The incidence of other musculoskeletal anomalies was much lower than of the spine (only 9% of the total). The triad of caudal regression-imperforate anus, spinal anomalies, and genitourinary tract anomalies-was present in 19 (53%) of the 36 cases, much more than any other combination of major system abnormalities such as the VATER of VACTEL syndromes.

  12. Congenital omental cyst

    PubMed Central

    Gupta, Rakesh Kumar; Sah, Suresh; Sah, Panna Lal; Shah, Birendra Prasad

    2012-01-01

    Congenital omental cysts are rare intra-abdominal pathology, which are difficult to diagnose preoperatively; as such a high index of suspicion is required for accurate preoperative diagnosis. We present a case of congenital omental cyst in a 3-year-old girl who presented with huge abdominal distension. We performed diagnostic examinations including ultrasonography and CT of the abdomen. An omental cyst was diagnosed because of its position and connection to the surrounding tissues. She was operated and cyst was excised completely. Histological examination revealed an omental cyst with endothelial lining and haemorrhagic fluid inside. She had an uneventful recovery and doing well, without recurrence at follow-up of 24 months. Clinicians must rigorously pursue a preoperative diagnosis, as it may prevent a surprise upon laparotomy and result in proper management. PMID:22865812

  13. Congenital Orbital Teratoma

    PubMed Central

    Pellerano, Fernando; Guillermo, Elvis; Garrido, Gloreley; Berges, Pedro

    2017-01-01

    We report a case of congenital orbital teratoma. A 3-day-old male, born at 39 weeks’ gestation without relevant prenatal history, presented with a large vascularized proptotic mass distorting the left midface. Laboratory studies showed elevated serum alpha-fetoprotein (12,910 ng/ml). Computed tomography showed a multiloculated heterogeneous lesion composed of hypodense and hyperdense calcified areas encompassing the whole orbital cavity with expansion of the bony walls, as well as forward displacement and compression of the eyeball without extension to surrounding structures. Clinical, imaging and laboratory features were consistent with congenital orbital teratoma. Due to pronounced proptosis with exposure keratopathy and corneal perforation, no motility of the globe and no vision in the affected eye in a resource-limited setting, the patient underwent orbital exenteration. Histopathological examination confirmed the diagnosis of mature cystic teratoma. We describe the clinical course, radiographic and histopathological findings of this rare orbital tumor. PMID:28275597

  14. Congenital Orbital Teratoma.

    PubMed

    Pellerano, Fernando; Guillermo, Elvis; Garrido, Gloreley; Berges, Pedro

    2017-01-01

    We report a case of congenital orbital teratoma. A 3-day-old male, born at 39 weeks' gestation without relevant prenatal history, presented with a large vascularized proptotic mass distorting the left midface. Laboratory studies showed elevated serum alpha-fetoprotein (12,910 ng/ml). Computed tomography showed a multiloculated heterogeneous lesion composed of hypodense and hyperdense calcified areas encompassing the whole orbital cavity with expansion of the bony walls, as well as forward displacement and compression of the eyeball without extension to surrounding structures. Clinical, imaging and laboratory features were consistent with congenital orbital teratoma. Due to pronounced proptosis with exposure keratopathy and corneal perforation, no motility of the globe and no vision in the affected eye in a resource-limited setting, the patient underwent orbital exenteration. Histopathological examination confirmed the diagnosis of mature cystic teratoma. We describe the clinical course, radiographic and histopathological findings of this rare orbital tumor.

  15. Congenital anomalies in Canada 2013: a perinatal health surveillance report by the Public Health Agency of Canada's Canadian Perinatal Surveillance System.

    PubMed

    Irvine, B; Luo, W; León, J A

    2015-03-01

    Congenital Anomalies in Canada 2013: A Perinatal Health Surveillance Report is the second national surveillance report from the Public Health Agency of Canada dedicated to congenital anomalies. It provides comprehensive data on congenital anomalies in Canada, focussing on 6 categories of congenital anomalies: Down syndrome, neural tube defects, congenital heart defects, orofacial clefts, limb deficiency defects and gastroschisis. The report presents national-level birth prevalence data and temporal trends, provincial and territorial estimates, and international comparisons. Known risk factors, prevalence-related impacts of prenatal diagnosis and preventative measures are also discussed.

  16. Leber congenital amaurosis.

    PubMed

    Perrault, I; Rozet, J M; Gerber, S; Ghazi, I; Leowski, C; Ducroq, D; Souied, E; Dufier, J L; Munnich, A; Kaplan, J

    1999-10-01

    Leber's congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies responsible for congenital blindness. Genetic heterogeneity of LCA has been suspected since the report by Waardenburg of normal children born to affected parents. In 1995, we localized the first disease causing gene, LCA1, to chromosome 17p13 and confirmed the genetic heterogeneity. In 1996, we ascribed LCA1 to mutations in the photoreceptor-specific guanylate cyclase gene (retGC1). RetGC1 is an essential protein implicated in the phototransduction cascade, especially in the recovery of the dark state after the excitation process of photoreceptor cells by light stimulation. In 1997, mutations in a second gene were reported in LCA, the RPE65 gene, which is the first specific retinal pigment epithelium gene. The protein RPE65 is implicated in the metabolism of vitamin A, the precursor of the photoexcitable retinal pigment (rhodopsin). Finally, a third gene, CRX, implicated in photoreceptor development, has been suspected of causing a few cases of LCA. Taken together, these three genes account for only 27% of LCA cases in our series. The three genes encode proteins that are involved in completely different physiopathologic pathways. Based on these striking differences of physiopathologic processes, we reexamined all clinical physiopathological discrepancies and the results strongly suggested that retGC1 gene mutations are responsible for congenital stationary severe cone-rod dystrophy, while RPE65 gene mutations are responsible for congenital severe but progressive rod-cone dystrophy. It is of tremendous importance to confirm and to refine these genotype-phenotype correlations on a large scale in order to anticipate the final outcome in a blind infant, on the one hand, and to further guide genetic studies in older patients on the other hand.

  17. Congenital amaurosis of Leber.

    PubMed

    Gillespie, F D

    1966-05-01

    In two families with congenital amaurosis of Leber, keratoglobus was found in all affected members and posterior subcapsular cataracts in most of them. Consanguinity was present in one family. Pathologic findings in one enucleated eye were presented. The literature on this disease was briefly reviewed. Whether the disease is a definite clinical or genetic entity and whether it might be an agenesis or an abiotrophy, or both, were discussed.

  18. Seminoma in Marfan's syndrome.

    PubMed Central

    Epenetos, A. A.; Collis, C. H.

    1979-01-01

    A patient with a testicular seminoma and Marfan's syndrome is described. The association is unlikely to be by chance alone, and an explanation in terms of either an associated congenital defect, or a minor chromosomal anomaly, is discussed. Images Fig. 1 Fig. 2 PMID:537969

  19. Congenital hearing loss.

    PubMed

    Korver, Anna M H; Smith, Richard J H; Van Camp, Guy; Schleiss, Mark R; Bitner-Glindzicz, Maria A K; Lustig, Lawrence R; Usami, Shin-Ichi; Boudewyns, An N

    2017-01-12

    Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing screening programmes enable early detection; early intervention will prevent delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life. A diagnosis of hearing loss is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus infection, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular, inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (the conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision making and guide prevention and (genetic) counselling. Management options include specific antimicrobial therapies, surgical treatment of craniofacial abnormalities and implantable or non-implantable hearing devices. An improved understanding of the pathophysiology and molecular mechanisms that underlie hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

  20. [Congenital insensitivity to pain].

    PubMed

    Popko, Janusz; Karpiński, Michał; Guszczyn, Tomasz

    2014-02-01

    Congenital insensitivity to pain belongs to rare diseases called hereditary sensory neuropathy (HSN). The disturbance of sense and secondary harms are creating clinical picture. The aim of this report was to describe therapeutic problems with which we met with a three siblings with congenital insensitivity to pain. The authors have described three children with congenital insensitivity to pain. The disease was diagnosed at the age of 3-5. These children painlessly have broken their lower limbs. These fractures were late diagnosed what resulted in a badly healed deformation of legs. For this reason, the right knee of the oldest boy had to be stiffened. This boy had also late diagnosed the left hip luxation, and hematomas had arisen, which become filled with pus. The boy was in sepsis and a dramatic life-and-death struggle was performed. A purulent focuses were removed from abdomen and femoral head was also resected. The other two siblings had fractures and infections, but not such severe as the oldest boy. It is well known that a causal treatment of this disease in unknown. Patients must learn to avoid mechanical and thermal trauma. It is the only way to prevent complications of this disease.