A position effect on TRPS1 is associated with Ambras syndrome in humans and the Koala phenotype in mice

PubMed Central

Fantauzzo, Katherine A.; Tadin-Strapps, Marija; You, Yun; Mentzer, Sarah E.; Baumeister, Friedrich A.M.; Cianfarani, Stefano; Van Maldergem, Lionel; Warburton, Dorothy; Sundberg, John P.; Christiano, Angela M.

2008-01-01

Ambras syndrome (AS) is a rare form of congenital hypertrichosis with excessive hair on the shoulders, face and ears. Cytogenetic studies have previously implicated an association with rearrangements of chromosome 8. Here we define an 11.5 Mb candidate interval for AS on chromosome 8q based on cytogenetic breakpoints in three patients. TRPS1, a gene within this interval, was deleted in a patient with an 8q23 chromosomal rearrangement, while its expression was significantly downregulated in another patient with an inversion breakpoint 7.3 Mb downstream of TRPS1. Here, we describe the first potential long-range position effect on the expression of TRPS1. To gain insight into the mechanisms by which Trps1 affects the hair follicle, we performed a detailed analysis of the hair abnormalities in Koa mice, a mouse model of hypertrichosis. We found that the proximal breakpoint of the Koa inversion is located 791 kb upstream of Trps1. Quantitative real-time polymerase chain reaction, in situ hybridization and immunofluorescence analysis revealed that Trps1 expression levels are reduced in Koa mutant mice at the sites of pathology for the phenotype. We determined that the Koa inversion creates a new Sp1 binding site and translocates additional Sp1 binding sites within a highly conserved stretch spanning the proximal breakpoint, providing a potential mechanism for the position effect. Collectively, these results describe a position effect that downregulates TRPS1 expression as the probable cause of hypertrichosis in AS in humans and the Koa phenotype in mice. PMID:18713754

The biodisposition and hypertrichotic effects of bimatoprost in mouse skin

PubMed Central

Woodward, David F; Tang, Elaine S-H; Attar, Mayssa; Wang, Jenny W

2013-01-01

Studies on bimatoprost were performed with two objectives: (i) to determine whether bimatoprost possesses hair growth-stimulating properties beyond eyelash hypertrichosis and (ii) to investigate the biodisposition of bimatoprost in skin for the first time. Bimatoprost, at the dose used clinically for eyelash growth (0.03%) and given once daily for 14 days, increased pelage hair growth in C57/black 6 mice. This occurred as a much earlier onset of new hair growth in shaved mice and the time taken to achieve complete hair regrowth, according to photographic documentation and visual assessment. Bimatoprost biodisposition in the skin was determined at three concentrations: 0.01%, 0.03% and 0.06%. Dose-dependent Cmax values were obtained (3.41, 6.74, 12.3 μg/g tissue), and cutaneous bimatoprost was well maintained for 24 h following a single dose. Bimatoprost was recovered from the skin only as the intact molecule, with no detectable levels of metabolites. Thus, bimatoprost produces hypertrichosis as the intact molecule. PMID:23278986

[H syndrome: First reported paediatric case in Latin America].

PubMed

Abarca Barriga, Hugo Hernán; Trubnykova, Milana; Polar Córdoba, Victoria; Ramos Diaz, Katherine Joyce; Aviles Alfaro, Nélida

H Syndrome is an extremely rare genetic disease, with a multisystemic character and which can be identified in early childhood, offering the opportunity of specific treatment and genetic counselling. To present a clinical case with "typical" characteristics of H Syndrome. The case is presented of an 8-year-old male patient who presented with testicular tumours and skin lesions characterised by hyperpigmentation with hypertrichosis, language delay, short stature, and joint deformities. He also presented with bilateral sensorineural hearing loss, anaemia, hypergammaglobulinaemia, and bone disorders. Histopathology studies of the skin and testicular masses reported lymphoplasmacytic infiltration. Sequencing analysis of gene SLC29A3 showed the homozygote mutation c.1087 C>T (p.Arg363Trp; rs387907067). These findings are consistent with H syndrome, and this is the first reported case in Latin America. The key to the diagnosis is the finding of hyperpigmentation with hypertrichosis. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations.

PubMed

Min Ko, Jung; Cho, Jae So; Yoo, Yongjin; Seo, Jieun; Choi, Murim; Chae, Jong-Hee; Lee, Hye-Ran; Cho, Tae-Joon

2017-02-01

Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.

Cloning of the breakpoints of a de novo inversion of chromosome 8, inv (8)(p11.2q23.1) in a patient with Ambras syndrome.

PubMed

Tadin-Strapps, M; Warburton, D; Baumeister, F A M; Fischer, S G; Yonan, J; Gilliam, T C; Christiano, A M

2004-01-01

Ambras syndrome (AMS) is a unique form of universal congenital hypertrichosis. In patients with this syndrome, the whole body is covered with fine long hair, except for areas where normally no hair grows. There is accompanying facial dysmorphism and teeth abnormalities, including retarded first and second dentition and absence of teeth. In 1993, Baumeister et al. reported an isolated case of Ambras syndrome in association with a pericentric inversion of chromosome 8. Subsequently, another patient with congenital hypertrichosis and rearrangement of chromosome 8 was reported by Balducci et al. (1998). Both of these patients have a breakpoint in 8q22 in common suggesting that this region of chromosome 8 contains a gene involved in regulation of hair growth. In order to precisely determine the nature of the rearrangement in the case of Ambras syndrome, we have used fluorescent in situ hybridization (FISH) analysis. We have cloned the inversion breakpoints in this patient and generated a detailed physical map of the inversion breakpoint interval. Analysis of the transcripts that map in the vicinity of the breakpoints revealed that the inversion does not disrupt a gene, and suggests that the phenotype is caused by a position effect. Copyright 2004 S. Karger AG, Basel

Barber-Say syndrome in a father and daughter.

PubMed

Roche, Nathalie; Houtmeyers, Philippe; Janssens, Sandra; Blondeel, Philllip

2010-10-01

We report on a father to daughter transmission of Barber-Say syndrome (BSS), a rare, congenital disorder characterized by severe generalized hypertrichosis, macrostomia, ocular telecanthus, bulbous nose and atrophic skin. These two cases further support the autosomal dominant inheritance. Both presented with the typical BSS symptoms but the phenotypic expression in the father was milder. Treatment is challenging for both patients and doctors, requiring a multidisciplinary approach. Copyright © 2010 Wiley-Liss, Inc.

[Complications of cosmetic skin bleaching in Africa].

PubMed

Morand, J J; Ly, F; Lightburn, E; Mahé, A

2007-12-01

Use of cosmetic products to bleach or lighten the skin is common among dark-skinned women in some sub-Saharan African countries. Long-term use of some pharmacologic compounds (e.g. hydroquinone, glucocorticoids and mercury) can cause adverse effects including dermatologic disorders such as dyschromia, exogenous ochronosis, acne and hypertrichosis, prominent striae, tinea corporis, pyoderma, erysipelas, scabies, and contact dermatitis and systemic complications such as hypertension, hypercorticism or surrenal deficiency, and mercurial nephropathy.

Alopecia: a review of laser and light therapies.

PubMed

Rangwala, Sophia; Rashid, Rashid M

2012-02-15

Since the 1980s, laser technology has become increasingly popular to treat a variety of cutaneous conditions. Its successful use as an epilator comes with the rare but interesting side effect of paradoxical hypertrichosis. In this review, we summarize cases describing hair growth after photoepilation, as well as studies testing laser and light sources as treatment for alopecia, particularly androgenetic alopecia and alopecia areata. We also discuss the possible biologic mechanisms by which phototherapy induces hair regeneration.

Myelodysplastic syndrome in an infant with constitutional pure duplication 1q41-qter.

PubMed

Morokawa, Hirokazu; Kamiya, Motoko; Wakui, Keiko; Kobayashi, Mikiko; Kurata, Takashi; Matsuda, Kazuyuki; Kawamura, Rie; Kanno, Hiroyuki; Fukushima, Yoshimitsu; Nakazawa, Yozo; Kosho, Tomoki

2018-01-01

We report on a Japanese female infant as the fourth patient with the constitutional pure duplication 1q41-qter confirmed by chromosomal microarray and as the first who developed myelodysplastic syndrome (MDS) among those with the constitutional 1q duplication. Common clinical features of the constitutional pure duplication 1q41-qter include developmental delay, craniofacial characteristics, foot malformation, hypertrichosis, and respiratory insufficiency. The association between MDS and the duplication of the genes in the 1q41-qter region remains unknown.

Two sisters resembling Gorlin-Chaudhry-Moss syndrome.

PubMed

Aravena, Teresa; Passalacqua, Cristóbal; Pizarro, Oscar; Aracena, Mariana

2011-10-01

The Gorlin-Chaudhry-Moss syndrome (GCMS), was describe initially by Gorlin et al. [Gorlin et al. (1960)] in two sisters with craniosynostosis, hypertrichosis, hypoplastic labia majora, dental defects, eye anomalies, patent ductus arteriosus, and normal intelligence. Two other sporadic instances have been documented. Here, we report on two sisters with a condition with some similarities to GCMS as well as some differences, which could represent either previously unreported variability in GCMS, or it may represent a novel disorder. Copyright © 2011 Wiley-Liss, Inc.

Multiple cutaneous hemangiomas in a patient with combined pituitary hormone deficiency.

PubMed

Aykut, Ayca; Ozen, Samim; Sımsek, Damla Gokşen; Onay, Huseyin; Cogulu, Ozgur; Darcan, Sukran; Ozkinay, Ferda

2014-01-01

Combined pituitary hormone deficiency (CPHD) refers to a rare heterogeneous group of conditions in which there is a deficiency in at least two anterior pituitary hormones. Patients with POU1F1 mutations show a combined pituitary deficiency with low or absent levels of growth hormone, prolactin, and thyroid-stimulating hormone. In this study, a 7-month-old girl with a CPHD is presented. She had facial dysmorphologic features, hypertrichosis, and hypotonia. Additionally, she also presented with multiple cutaneous hemangioma that until now has not been reported in association with this disorder.

Paraneoplastic cutaneous manifestations: concepts and updates*

PubMed Central

da Silva, Josenilson Antônio; Mesquita, Kleyton de Carvalho; Igreja, Ana Carolina de Souza Machado; Lucas, Isabella Cristina Rodrigues Naves; Freitas, Aline Ferreira; de Oliveira, Sandra Maximiano; Costa, Izelda Maria Carvalho; Campbell, Iphis Tenfuss

2013-01-01

The skin often signals systemic changes. Some neoplastic diseases that affect internal organs may trigger several cutaneous manifestations. Although these dermatoses are relatively unusual, the recognition of some typical paraneoplastic dermatoses may lead to the early diagnosis of a neoplasm and determine a better prognosis. In this review article, we discuss the paraneoplastic cutaneous manifestations strongly associated with neoplasms, which include acanthosis nigricans maligna, tripe palms, erythema gyratum repens, Bazex syndrome, acquired hypertrichosis lanuginosa, necrolytic migratory erythema, Leser-Trélat sign and paraneoplastic pemphigus. We also review the clinical manifestations of each condition and include updated knowledge on disease pathogenesis. PMID:23538999

Successful treatment of eosinophilic pustular folliculitis with topical tacrolimus 0.1 percent ointment.

PubMed

Ng, Shanna Shan-Yi; Tay, Yong-Kwang

2012-02-15

Classic eosinophilic pustular folliculitis (EPF), otherwise known as Ofugi disease, is a rare condition commonly treated with topical glucocorticosteroids. If this fails, oral indomethacin is frequently the next line. Because the condition is recurrent, the use of long term steroids may cause side effects such as skin atrophy, hypertrichosis, and dyspigmentation. Topical tacrolimus is an immunosuppressant that is generally used as a steroid-sparing agent in atopic dermatitis. We report a case of classic EPF, which was recurrent over 5 years that had failed topical glucocorticosteroids but was successfully treated with topical tacrolimus 0.1 percent ointment.

Overdose of Rogaine Extra Strength for Men topical minoxidil preparation.

PubMed

Farrell, S E; Epstein, S K

1999-01-01

Minoxidil is a potent arterial vasodilator used in the treatment of hypertension. A side effect, hypertrichosis, has prompted the marketing of a topical preparation, Rogaine, for the treatment of male-pattern baldness. Recently, a 5% solution of minoxidil became available over-the-counter as Rogaine Extra Strength For Men Hair Regrowth Treatment. We describe an oral overdose of minoxidil 3 g as the Rogaine Extra Strength preparation. Toxicity manifested as profound hypotension, requiring vasopressor support, intubation, prolonged tachycardia, and fluid overload with pleural effusions, requiring several days of therapy with furosemide. This is the largest reported ingestion of minoxidil and the first reported overdose of the extra strength 5% solution.

Berardinelli-Seip congenital lipodystrophy in two siblings

PubMed Central

Rao, T. S. Mohana; Chennamsetty, Kavya

2014-01-01

Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare autosomal recessive disorder characterized by various dermatological and systemic manifestations such as lipoatrophy, hypertriglyceridemia, hepatomegaly, acanthosis nigricans, and acromegaloid features. BSCL type 2 is more common and severe, with onset in the neonatal period or in early infancy. The locus for BSCL2 has been identified on chromosome 11q13. Early recognition and differentiation from other congenital generalized lipodystrophies help in the initiation of appropriate preventive and therapeutic measures such as lifestyle modification and pharmacotherapy that helps postpone the onset of metabolic syndrome. We report BSCL type 2 in two siblings with several cutaneous manifestations like acanthosis nigricans, hypertrichosis, prominent subcutaneous veins, and increased lanugo hair. PMID:25506557

Congenital Becker's nevus with a familial association.

PubMed

Book, S E; Glass, A T; Laude, T A

1997-01-01

Becker's nevus is a unilateral, hyperpigmented cutaneous hamartoma usually with hypertrichosis. It occurs predominantly in boys, becoming apparent during adolescence, although several cases of congenital Becker's nevus have been reported. Rarely it may be familial and as such is transmitted in an autosomal dominant pattern. We report a 16-month-old black boy with a hyperpigmented patch on his right shoulder and upper pectoral area that extended down his arm. The patient's father has a similar lesion with hair on his left shoulder which has been present since childhood. Histology of the child's lesion was consistent with Becker's nevus. We believe this to be the first reported case of a congenital Becker's nevus with a familial association.

Promising alternative clinical uses of prostaglandin F2α analogs: beyond the eyelashes.

PubMed

Choi, Young M; Diehl, Joseph; Levins, Paul C

2015-04-01

Prostaglandin F2α analogs, commonly prescribed for glaucoma treatment, have been shown to induce side effects such as cutaneous hypertrichosis and hyperpigmentation. Therefore, these medications have theoretic applications in the treatment of alopecia and disorders of hypopigmentation. We reviewed the literature to find original studies assessing the use of prostaglandin F2α analogs in these settings. Studies and reports were analyzed in regards to androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring. Based on the results of these studies, and consideration of pathophysiologic mechanism, the most promising applications for prostaglandin F2α analogs include androgenic alopecia, chemotherapy-induced alopecia, and alopecia areata concurrently treated with corticosteroids. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Retrospective Evaluation of Topical Bimatoprost and Iris Pigmentation Change.

PubMed

Zaleski-Larsen, Lisa A; Ruth, Nadine H; Fabi, Sabrina G

2017-12-01

Topical bimatoprost is a topical prostaglandin analog originally used to treat glaucoma and more recently used to cosmetically induce hypertrichosis of the eyelashes. Iris pigmentation change has been noted in the treatment of glaucoma but has not been assessed with the cosmetic periorbital application of bimatoprost. To evaluate for iris pigmentation change with the long-term cosmetic use of topical bimatoprost. A retrospective chart review in a cosmetic dermatology practice of women (N = 50) who consistently purchased topical bimatoprost over an average of 4.59 years was compared with that of age-matched non-bimatoprost patients (N = 50). A blinded evaluator assessed each patient for iris pigmentary change. No iris pigmentation change was noted with the cutaneous application of bimatoprost. The cutaneous application of bimatoprost appears to be safe with minimal risk for iris pigmentation change.

Ophthalmologic Findings in H Syndrome: A Unique Diagnostic Clue.

PubMed

Molho-Pessach, Vered; Mechoulam, Hadas; Siam, Rula; Babay, Sofia; Ramot, Yuval; Zlotogorski, Abraham

2015-01-01

H syndrome is an autosomal recessive histiocytosis with multisystemic involvement caused by mutations in the SLC29A3 gene. The term H syndrome was coined to denote the major clinical findings which include hyperpigmentation, hypertrichosis, hearing loss, hepatosplenomegaly, hypogonadism, hyperglycemia/diabetes mellitus and hallux valgus/flexion contractures. Almost 100 individuals affected with this disorder have been reported, however, a thorough evaluation of the ophthalmologic features of H syndrome has not yet been performed. Ophthalmic examination of a 50-year-old male with H syndrome. Mutation analysis of SLC29A3 was also performed in this patient. Ophthalmic findings included; shallow orbits with exorbitism, bilateral pterygium, limbal thickening, corneal arcus and cortical cataract. We also review ophthalmologic findings in previously reported H syndrome patients. The presence of dilated lateral scleral vessels, corneal arcus and shallow orbits should raise the suspicion of H syndrome, especially when seen in young age.

First report of a patient with a mixoploidy 47,XXX/94,XXXXXX.

PubMed

Rodríguez Criado, G; Galán Gómez, E; Tizzano, E F; García Rodríguez, E; Gómez de Terreros, I

2007-01-01

We present a 16 years old female with a chromosomal mixoploidy and multiple phenotypic anomalies. Peripheral blood G-band karyotype was 47,XXX and her skin fibroblast karyotype revealed a mosaic with a 47,XXX cell line in 88% of metaphases and a 94,XXXXXX cell line in 12% of metaphases, consistent with a hypertetraploidy. The most prominent clinical signs were: short stature, left upper limb asymmetry, senile-like appearance, generalized hypertrichosis, and small hands and feet. Radiological examination showed bone dysplasia. The result of molecular studies demonstrated that the patient inherited the two X chromosomes from the mother and one from the father, indicating that her 47,XXX trisomy resulted from an oogenesis error in the first meiotic division. The 94,XXXXXX cell line was likely the result of a cytokinesis error. To our knowledge, this is the first documented patient with a trisomy and a hypertetraploidy.

Clinical Management of Patients with ASXL1 Mutations and Bohring-Opitz Syndrome, Emphasizing the Need for Wilms Tumor Surveillance

PubMed Central

Russell, Bianca; Johnston, Jennifer J; Biesecker, Leslie G.; Kramer, Nancy; Pickart, Angela; Rhead, William; Tan, Wen-Hann; Brownstein, Catherine A; Clarkson, L Kate; Dobson, Amy; Rosenberg, Avi Z; Schrier Vergano, Samantha A.; Helm, Benjamin M.; Harrison, Rachel E; Graham, John M

2016-01-01

Bohring-Opitz syndrome is a rare genetic condition characterized by distinctive facial features, variable microcephaly, hypertrichosis, nevus flammeus, severe myopia, unusual posture (flexion at the elbows with ulnar deviation, and flexion of the wrists and metacarpophalangeal joints), severe intellectual disability, and feeding issues. Nine patients with Bohring-Opitz syndrome have been identified as having a mutation in ASXL1. We report on eight previously unpublished patients with Bohring-Opitz syndrome caused by an apparent or confirmed de novo mutation in ASXL1. Of note, two patients developed bilateral Wilms tumors. Somatic mutations in ASXL1 are associated with myeloid malignancies, and these reports emphasize the need for Wilms tumor screening in patients with ASXL1 mutations. We discuss clinical management with a focus on their feeding issues, cyclic vomiting, respiratory infections, insomnia, and tumor predisposition. Many patients are noted to have distinctive personalities (interactive, happy, and curious) and rapid hair growth; features not previously reported. PMID:25921057

Dominant missense mutations in ABCC9 cause Cantú syndrome.

PubMed

Harakalova, Magdalena; van Harssel, Jeske J T; Terhal, Paulien A; van Lieshout, Stef; Duran, Karen; Renkens, Ivo; Amor, David J; Wilson, Louise C; Kirk, Edwin P; Turner, Claire L S; Shears, Debbie; Garcia-Minaur, Sixto; Lees, Melissa M; Ross, Alison; Venselaar, Hanka; Vriend, Gert; Takanari, Hiroki; Rook, Martin B; van der Heyden, Marcel A G; Asselbergs, Folkert W; Breur, Hans M; Swinkels, Marielle E; Scurr, Ingrid J; Smithson, Sarah F; Knoers, Nine V; van der Smagt, Jasper J; Nijman, Isaac J; Kloosterman, Wigard P; van Haelst, Mieke M; van Haaften, Gijs; Cuppen, Edwin

2012-05-18

Cantú syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantú syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantú syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantú syndrome.

Systematic review of low-level laser therapy for adult androgenic alopecia.

PubMed

Delaney, Sean W; Zhang, Paul

2017-12-29

Alopecia is a common disorder affecting over half of the world's population. Within this condition, androgenic alopecia (AA) is the most common type, affecting 50% of males over 40 and 75% of females over 65. Anecdotal paradoxical hypertrichosis noted during laser epilation has generated interest in the possibility of using laser to stimulate hair growth. In this study, we aimed to critically appraise the application of low-level laser therapy for the treatment of AA in adults. A systematic review was performed on studies identified on Medline, EMBASE, Cochrane database, and clinicaltrials.org. Double-blinded randomized controlled trials were selected and analyzed quantitatively (meta-analysis) and qualitatively (quality of evidence, risk of bias). Low-level laser therapy appears to be a promising noninvasive treatment for AA in adults that is safe for self-administration in the home setting. Although shown to effectively stimulate hair growth when compared to sham devices, these results must be interpreted with caution. Further studies with larger samples, longer follow-up, and independent funding sources are necessary to determine the clinical effectiveness of this novel therapy.

[Hormones and hair growth].

PubMed

Trüeb, R M

2010-06-01

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

Ciclosporin use in multi-drug therapy for meningoencephalomyelitis of unknown aetiology in dogs.

PubMed

Adamo, P F; Rylander, H; Adams, W M

2007-09-01

To evaluate the efficacy and safety of ciclosporin therapy alone or in combination with corticosteroids and/or ketoconazole in dogs with diagnosis of meningoencephalomyelitis of unknown aetiology. Medical records of 10 dogs diagnosed with meningoencephalomyelitis of unknown aetiology and treated with ciclosporin therapy alone or in combination with corticosteroids and/or ketoconazole were reviewed at the Veterinary Medical Teaching Hospital, University of Wisconsin-Madison. Laboratory abnormalities, side effects, clinical and cerebrospinal fluid responses to treatment and association between blood ciclosporin level and response to treatment were evaluated. Histopathological diagnosis was available in three patients. No significant abnormalities were detected on serial complete blood count and serum chemistry panel in any of the dogs. Side effects of ciclosporin therapy included excessive shedding, gingival hyperplasia and hypertrichosis. Overall median survival time for all dogs in the study was 930 days (range, 60 to more than 1290 days). In all dogs, serial cerebrospinal fluid analysis showed a marked improvement in the inflammation. Results suggest that ciclosporin either alone or in combination with ketoconazole may be a safe and effective treatment for meningoencephalomyelitis of unknown aetiology in dogs.

[Efficacy and tolerability of 5% minoxidil solution (Carexidil®) in male and female androgenetic alopecia: a 6-month open multicentric study].

PubMed

Piraccini, B; Starace, M; Alessandrini, A; Guarrera, M; Fiorucci, M C; Lorenzi, S

2011-12-01

The aim of the study was to evaluate efficacy and safety of 5% Carexidil solution®, applied twice a day on the scalp, on male and female androgenetic alopecia. The 6 month-study was performed in three Italian dermatological centers. Evaluation of efficacy was performed with subjective and objective methods, including operator and patient assessments, global photography and videodermoscopy. Global photography revealed that after 6 months of treatment with 5% Carexidil solution®, androgenetic alopecia was improved in all 32 females and 16 males. Alopecia stopped to progress in 6 males. Scalp videodermoscopy confirmed the results. Some patients complained of increased hair greasiness, others complained of mild scalp itching. Two female patients developed contact sensitization to minoxidil, confirmed by patch test, 2 a mild malar-temporal hypertrichosis. All patients were satisfied by treatment and continued it after the end of the study. Our study confirms the data of the literature and the evidence coming from years of clinical experience, that twice a day topical application of 5% minoxidil solution, Carexidil ®, is effective in the treatment of male and female androgenetic alopecia, with evident efficacy already after 6 months.

Mutations in the Cholesterol Transporter Gene ABCA5 Are Associated with Excessive Hair Overgrowth

PubMed Central

DeStefano, Gina M.; Kurban, Mazen; Anyane-Yeboa, Kwame; Dall'Armi, Claudia; Di Paolo, Gilbert; Feenstra, Heather; Silverberg, Nanette; Rohena, Luis; López-Cepeda, Larissa D.; Jobanputra, Vaidehi; Fantauzzo, Katherine A.; Kiuru, Maija; Tadin-Strapps, Marija; Sobrino, Antonio; Vitebsky, Anna; Warburton, Dorothy; Levy, Brynn; Salas-Alanis, Julio C.; Christiano, Angela M.

2014-01-01

Inherited hypertrichoses are rare syndromes characterized by excessive hair growth that does not result from androgen stimulation, and are often associated with additional congenital abnormalities. In this study, we investigated the genetic defect in a case of autosomal recessive congenital generalized hypertrichosis terminalis (CGHT) (OMIM135400) using whole-exome sequencing. We identified a single base pair substitution in the 5′ donor splice site of intron 32 in the ABC lipid transporter gene ABCA5 that leads to aberrant splicing of the transcript and a decrease in protein levels throughout patient hair follicles. The homozygous recessive disruption of ABCA5 leads to reduced lysosome function, which results in an accumulation of autophagosomes, autophagosomal cargos as well as increased endolysosomal cholesterol in CGHT keratinocytes. In an unrelated sporadic case of CGHT, we identified a 1.3 Mb cryptic deletion of chr17q24.2-q24.3 encompassing ABCA5 and found that ABCA5 levels are dramatically reduced throughout patient hair follicles. Collectively, our findings support ABCA5 as a gene underlying the CGHT phenotype and suggest a novel, previously unrecognized role for this gene in regulating hair growth. PMID:24831815

The role of community pharmacists in the management of hematopoietic stem cell transplant recipients: knowledge and training.

PubMed

Prot-Labarthe, Sonia; Stil-Baudry, Julien; Fahd, Mony; Brion, Françoise; Bourdon, Olivier

2013-04-01

The patients receiving hematopoietic stem cell transplantation (HSCT) require routine management: the role of the pharmacist has not been extensively considered. This study had 2 aims: to explore the knowledge of community pharmacists relating to pediatric HSCT and to evaluate their expectations in terms of training needs. We interviewed 40 community pharmacists in May and June 2010 in Paris (France) with a 3 parts questionnaire: information concerning the community pharmacy, analysis of 2 pediatric prescriptions and knowledge about HSCT and professional training. Twenty-nine (72.5%) of the 40 community pharmacies agreed to participate in the study. When asked what pharmacological advice they would give for an episode of fever, 13% of the pharmacists asked said that they would deliver acetaminophen without asking any further questions. Concerning hypertrichosis in patients treated with corticosteroids and ciclosporin, none mentioned the role of ciclosporin. The erroneous indications for HSCT given included road accidents (1 pharmacist; 3.4%) and hemophilia (3 pharmacists; 10.3%). Almost 80% of the pharmacists questioned considered their HSCT knowledge insufficient for their professional practice. An E-learning session adapted to their needs was of interest to almost three quarters of the pharmacists questioned.

Leigh and Leigh-like syndrome in children and adults.

PubMed

Finsterer, Josef

2008-10-01

Leigh syndrome (also termed subacute, necrotizing encephalopathy) is a devastating neurodegenerative disorder, characterized by almost identical brain changes, e.g., focal, bilaterally symmetric lesions, particularly in the basal ganglia, thalamus, and brainstem, but with considerable clinical and genetic heterogeneity. Clinically, Leigh syndrome is characterized by a wide variety of abnormalities, from severe neurologic problems to a near absence of abnormalities. Most frequently the central nervous system is affected, with psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure. Some patients also present with peripheral nervous system involvement, including polyneuropathy or myopathy, or non-neurologic abnormalities, e.g., diabetes, short stature, hypertrichosis, cardiomyopathy, anemia, renal failure, vomiting, or diarrhea (Leigh-like syndrome). In the majority of cases, onset is in early childhood, but in a small number of cases, adults are affected. In the majority of cases, dysfunction of the respiratory chain (particularly complexes I, II, IV, or V), of coenzyme Q, or of the pyruvate dehydrogenase complex are responsible for the disease. Associated mutations affect genes of the mitochondrial or nuclear genome. Leigh syndrome and Leigh-like syndrome are the mitochondrial disorders with the largest genetic heterogeneity.

Cantú Syndrome Resulting from Activating Mutation in the KCNJ8 Gene

PubMed Central

Cooper, Paige E.; Reutter, Heiko; Woelfle, Joachim; Engels, Hartmut; Grange, Dorothy K.; van Haaften, Gijs; van Bon, Bregje W.; Hoischen, Alexander; Nichols, Colin G.

2014-01-01

ATP-sensitive potassium (KATP) channels, composed of inward-rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutations in ABCC9 cause Cantú syndrome, a distinct multi-organ disease, potentially via enhanced KATP channel activity. We screened KCNJ8 in an ABCC9 mutation-negative patient who also exhibited clinical hallmarks of Cantú syndrome (hypertrichosis, macrosomia, macrocephaly, coarse facial appearance, cardiomegaly, and skeletal abnormalities). We identified a de novo missense mutation encoding Kir6.1[p.Cys176Ser] in the patient. Kir6.1[p.Cys176Ser] channels exhibited markedly higher activity than wild-type channels, as a result of reduced ATP sensitivity, whether co-expressed with SUR1 or SUR2A subunits. Our results identify a novel causal gene in Cantú syndrome, but also demonstrate that the cardinal features of the disease result from gain of KATP channel function, not from Kir6-independent SUR2 function. PMID:24700710

Cantú syndrome resulting from activating mutation in the KCNJ8 gene.

PubMed

Cooper, Paige E; Reutter, Heiko; Woelfle, Joachim; Engels, Hartmut; Grange, Dorothy K; van Haaften, Gijs; van Bon, Bregje W; Hoischen, Alexander; Nichols, Colin G

2014-07-01

ATP-sensitive potassium (KATP ) channels, composed of inward-rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutations in ABCC9 cause Cantú syndrome (CS), a distinct multiorgan disease, potentially via enhanced KATP channel activity. We screened KCNJ8 in an ABCC9 mutation-negative patient who also exhibited clinical hallmarks of CS (hypertrichosis, macrosomia, macrocephaly, coarse facial appearance, cardiomegaly, and skeletal abnormalities). We identified a de novo missense mutation encoding Kir6.1[p.Cys176Ser] in the patient. Kir6.1[p.Cys176Ser] channels exhibited markedly higher activity than wild-type channels, as a result of reduced ATP sensitivity, whether coexpressed with SUR1 or SUR2A subunits. Our results identify a novel causal gene in CS, but also demonstrate that the cardinal features of the disease result from gain of KATP channel function, not from a Kir6-independent SUR2 function. © 2014 WILEY PERIODICALS, INC.

'A WONDERFULL MONSTER BORNE IN GERMANY': HAIRY GIRLS IN MEDIEVAL AND EARLY MODERN GERMAN BOOK, COURT AND PERFORMANCE CULTURE.

PubMed

Katritzky, M A

2014-09-24

Human hirsuteness, or pathological hair growth, can be symptomatic of various conditions, including genetic mutation or inheritance, and some cancers and hormonal disturbances. Modern investigations into hirsuteness were initiated by nineteenth-century German physicians. Most early modern European cases of hypertrichosis (genetically determined all-over body and facial hair) involve German-speaking parentage or patronage, and are documented in German print culture. Through the Wild Man tradition, modern historians routinely link early modern reception of historical hypertrichosis cases to issues of ethnicity without, however, recognising early modern awareness of links between temporary hirsuteness and the pathological nexus of starvation and anorexia. Here, four cases of hirsute females are reconsidered with reference to this medical perspective, and to texts and images uncovered by my current research at the Herzog August Library and German archives. One concerns an Italian girl taken to Prague in 1355 by the Holy Roman Empress, Anna von Schweidnitz. Another focuses on Madeleine and Antonietta Gonzalez, daughters of the 'Wild Man' of Tenerife, documented at German courts in the 1580s. The third and fourth cases consider the medieval bearded Sankt Kümmernis (also known as St Wilgefortis or St Uncumber), and the seventeenth-century Bavarian fairground performer Barbara Urslerin. Krankhafter menschlicher Hirsutismus kann aufgrund unterschiedlicher Ursachen auftreten, zu denen u.a. genetische Veländerungen und Vererbung, verschiedene Krebserkrankungen und hormonelle Störungen gehören. Die moderne Hirsutismus-Forschung ist im 19. Jh. von deutschen Forschern initiiert worden. Die meisten europäischen frühneuzeitlichen Erscheinungen von Hypertrichose (dem genetisch bedingten Haarwuchs am gesamten Körper und im Gesicht) gehen auf deutschsprachige Eltern oder Förderer zurück und sind in Deutschland in den Druck gelangt. Bei Untersuchungen des Motivs des Wilden

‘A Wonderfull Monster Borne in Germany’: Hairy Girls in Medieval and Early Modern German Book, Court and Performance Culture*

PubMed Central

Katritzky, MA

2014-01-01

Human hirsuteness, or pathological hair growth, can be symptomatic of various conditions, including genetic mutation or inheritance, and some cancers and hormonal disturbances. Modern investigations into hirsuteness were initiated by nineteenth-century German physicians. Most early modern European cases of hypertrichosis (genetically determined all-over body and facial hair) involve German-speaking parentage or patronage, and are documented in German print culture. Through the Wild Man tradition, modern historians routinely link early modern reception of historical hypertrichosis cases to issues of ethnicity without, however, recognising early modern awareness of links between temporary hirsuteness and the pathological nexus of starvation and anorexia. Here, four cases of hirsute females are reconsidered with reference to this medical perspective, and to texts and images uncovered by my current research at the Herzog August Library and German archives. One concerns an Italian girl taken to Prague in 1355 by the Holy Roman Empress, Anna von Schweidnitz. Another focuses on Madeleine and Antonietta Gonzalez, daughters of the ‘Wild Man’ of Tenerife, documented at German courts in the 1580s. The third and fourth cases consider the medieval bearded Sankt Kümmernis (also known as St Wilgefortis or St Uncumber), and the seventeenth-century Bavarian fairground performer Barbara Urslerin. Krankhafter menschlicher Hirsutismus kann aufgrund unterschiedlicher Ursachen auftreten, zu denen u.a. genetische Veränderungen und Vererbung, verschiedene Krebserkrankungen und hormonelle Störungen gehören. Die moderne Hirsutismus-Forschung ist im 19. Jh. von deutschen Forschern initiiert worden. Die meisten europäischen frühneuzeitlichen Erscheinungen von Hypertrichose (dem genetisch bedingten Haarwuchs am gesamten Körper und im Gesicht) gehen auf deutschsprachige Eltern oder Förderer zurück und sind in Deutschland in den Druck gelangt. Bei Untersuchungen des Motivs des

Bimatoprost in the treatment of eyelash hypotrichosis

PubMed Central

Law, Simon K

2010-01-01

Eyelashes hypotrichosis is a condition indicated by an inadequate amount of eyelashes. Hypertrichosis of eyelashes, characterized by excessive eyelash growth, is a regular phenomenon associated with ophthalmic prostaglandin and prostamide analogs. Recently, the US Food and Drug Administration approved Latisse® (bimatoprost 0.03% solution), identical to the ophthalmic solution for glaucoma treatment, for increasing eyelash length, thickness and darkness in patients with hypotrichosis of the eyelashes. When prostaglandin and prostamide analogs interact with the prostanoid receptors in the hair follicle, this most likely stimulates the resting follicles (telogen phase) to growing follicles (anagen phase). Prostaglandin and prostamide analogs may also prolong the anagen phase of eyelashes, leading to an increase of eyelash length. Although bimatoprost is effective in promoting increased growth of healthy eyelashes and adnexal hairs, its effectiveness in patients with eyelash alopecia areata is debatable and its protective effect is not yet studied in patients with eyelash loss secondary to radiation or chemotherapy. Bimatoprost is generally safe when applied to the base of the eyelashes at the lid margin with minimum side effects. However, other ocular or systemic side effects associated with ophthalmic prostaglandin and prostamide analogs may occur when instilled on the surface of the eye, and patients must be informed and monitored. PMID:20463804

Minoxidil: an underused vasodilator for resistant or severe hypertension.

PubMed

Sica, Domenic A

2004-05-01

Minoxidil is a direct vasodilator introduced in the early 1970s for the treatment of hypertension. It is capable of reducing blood pressure in most persons with resistant hypertension where therapy has failed with multidrug regimens. Minoxidil's effect can be limited because of an increase in pulse rate and/or sodium (and water) retention. The latter may prove quite debilitating in some patients. Thus, minoxidil is generally administered with both a diuretic and an agent that can keep pulse rate in check, such as a beta blocker or a combined alpha-beta blocker. The prominent tachycardia with minoxidil can aggravate myocardial ischemia and, if long-standing, leads to left ventricular hypertrophy. Minoxidil has a particularly annoying side effect of hypertrichosis that may limit its use, particularly among women. Minoxidil use is infrequently associated with the idiosyncratic onset of a pericardial effusion. If a patient's hypertension is severe enough to warrant minoxidil therapy, a hypertension specialist should probably become involved in the patient's care. The use of this medication should be limited in view of the availability of effective agents with fewer side effects. There is, however, a place for minoxidil in the treatment of resistant hypertension especially in patients with advanced renal disease.

A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PubMed

Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

2015-09-01

Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

Hair and Scalp Disorders in a Tuscan Pediatric Dermatological Outpatient Clinic: A Clinical and Epidemiological Evaluation.

PubMed

Conti, Rossana; Colucci, Roberta; Arunachalam, Meena; Berti, Samantha; Fabroni, Caterina; De Martino, Maurizio; Dragoni, Federica; Lazzeri, Linda; Pisaneschi, Lisa; Moretti, Silvia

2016-01-01

The aim of this study was to evaluate the clinical and epidemiological profile of hair and scalp disorders in children referred to the Pediatric Dermatology Outpatient Clinic. We performed a retrospective study of children with hair loss problems or scalp diseases who turned to the Pediatric Dermatology Service, Anna Meyer Pediatric Hospital, Florence, Italy, from January 1, 2009, to December 31, 2009. Demographics, personal and familial medical history, laboratory tests, clinical examination, final diagnosis and therapeutic interventions were obtained from the manual chart review. Of the 2,640 children who had access to the Pediatric Dermatology Service, 190 (7.19%) had a hair or scalp disorder. Among the 190 children, 60 (31.57%) presented with nonscarring alopecia, 56 (29.47%) had benign neoplasias, hamartomas or vascular malformations of the scalp, 51 (26.84%) had scalp inflammatory diseases, 14 (7.36%) had scarring alopecia, 5 (2.63%) had infections and 2 (1.05%) had infestation of the scalp. A case of constitutional hypertrichosis (0.52%) and also a case (0.52%) of lamellar ichthyosis were diagnosed. Our results underline that hair and scalp diseases represent an important percentage of admittances to a dermatological pediatric outpatient clinic. The variety and complexity of the diseases observed in this study included diseases commonly found also in adulthood. © 2015 S. Karger AG, Basel.

Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiency.

PubMed

Yüksel, Adnan; Seven, Mehmet; Cetincelik, Umran; Yeşil, Gözde; Köksal, Vedat

2006-06-01

Leigh syndrome is an inherited, progressive neurodegenerative disorder of infancy and childhood. Mutations in the nuclear SURF-1 gene are specifically associated with cytochrome C oxidase-deficient Leigh syndrome. This report describes two patients with similar facial features. One of them was a 2(1/2)-year-old male, and the other was a 3-year-old male with a mutation in SURF-1 gene and facial dysmorphism including frontal bossing, brachycephaly, hypertrichosis, lateral displacement of inner canthi, esotropia, maxillary hypoplasia, hypertrophic gums, irregularly placed teeth, upturned nostril, low-set big ears, and retrognathi. The first patient's magnetic resonance imaging at 15 months of age indicated mild symmetric T2 prolongation involving the subthalamic nuclei. His second magnetic resonance imaging at 2 years old revealed a symmetric T2 prolongation involving the subthalamic nuclei, substantia nigra, and medulla lesions. In the second child, at the age of 2 the first magnetic resonance imaging documented heavy brainstem and subthalamic nuclei involvement. A second magnetic resonance imaging, performed when he was 3 years old, revealed diffuse involvement of the substantia nigra and hyperintense lesions of the central tegmental tract in addition to previous lesions. Facial dysmorphism and magnetic resonance imaging findings, observed in these cases, can be specific findings in Leigh syndrome patients with cytochrome C oxidase deficiency. SURF-1 gene mutations must be particularly reviewed in such patients.

[Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics].

PubMed

Tsygankova, P G; Mikhaĭlova, S V; Zakharova, E Iu; Pichkur, N A; Il'ina, E S; Nikolaeva, E A; Rudenskaia, G E; Dadali, E L; Kolpakchi, L M; Fedoniuk, I D; Matiushchenko, G N

2010-01-01

Syndrome Leigh (SL) or subacute necrotizing encephalomyelopathy - is a rare hereditary genetically heterogeneous disease from the group of mitochondrial encephalomyopathies. Twenty-seven children with SL were examined using clinical, laboratory (measuring lactate levels), MRI and molecular-genetic (polymerase chain reaction genotyping of 9 exons of the SURF1 gene) studies. The mean age of manifestation was 11,6 months. The main manifestations of SL were: delay of psychomotor development, diffuse muscle hypertonic, cerebellar syndrome, ophthalmoparesis, hypertrichosis. The disease had a progressive course with the loss of acquired skills. The blood lactate concentration was increased on average up to 3,1 mM/ml (from 1,9 to 5,1 mM/ml) compared to normal values (1,8 mM/ml). Brain MRI revealed the subcortical and cortical atrophy (80% of cases), symmetrical distinctly delineated hyperintense lesions on T2-weighted images (demyelization) in the basal ganglia and the brain stem (50%), as well as in the cerebellum (25%). Genotyping identified 7 different mutations. The most frequent (64,8%) was the deletion of 2 nucleotides (845delCT) in exon 8 that was in line with early data of Polish researchers thus indicating the Slavic origin of this mutation. Other mutations (574-575insCTGT, 311-321del10insAT and IVS8-1G>) were also frequent in the Russian population.

Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene

PubMed Central

Sonmez, Fatma Mujgan; Uctepe, Eyyup; Gunduz, Mehmet; Gormez, Zeliha; Erpolat, Seval; Oznur, Murat; Sagiroglu, Mahmut Samil; Demirci, Huseyin; Gunduz, Esra

2016-01-01

Summary Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better. PMID:27672547

Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene.

PubMed

Sonmez, Fatma Mujgan; Uctepe, Eyyup; Gunduz, Mehmet; Gormez, Zeliha; Erpolat, Seval; Oznur, Murat; Sagiroglu, Mahmut Samil; Demirci, Huseyin; Gunduz, Esra

2016-08-01

Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better.

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

[From teratology to mythology: ancient legends].

PubMed

Stahl, A; Tourame, P

2010-12-01

The mythology of the Greeks and Romans is full of monsters of fiction: giants, cyclops, centaurs, hydras, Gorgons… The accounts of travelers, reproduced in the Natural History of Pline l'Ancien reported the existence, in distant countries, of men with a dog's head (baboons), of men with a single tall foot (sciapode), beings whose face is embedded in the chest (or acephala blemmyes), to which must be added a wide variety of men with no mouth, no nose, or equipped with giant ears or feet turned backwards, as well as hermaphrodites. Teratology reports on monstrous births, which have constituted the factual basis from which the imagination conceived adults whose morphology corresponds to the monsters of legend. Newborns sirenomelia were behind the legend of sciapode and sirens. Cyclopia have inspired the legend of the cyclops. Anencephaly probably explains the description of headless or blemmyes. The genesis of the legend of baboons may have multiple origins: firstly the existence of people suffering from congenital hypertrichosis, on the other hand, the influence of Egyptian mythology where the god Anubis has a dog's head. The acardiac fetus may explain some monstrous forms, features the work of Hieronymus Bosch. The significance of the monsters of legend, their genesis, their persistence through the ages is complex. By approaching teratology, we added a new field of exploration of real monsters of antiquity and Middle Ages. Copyright © 2010. Published by Elsevier SAS.

Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations.

PubMed

Sonam, Kothari; Khan, Nahid Akthar; Bindu, Parayil Sankaran; Taly, Arun B; Gayathri, N; Bharath, M M Srinivas; Govindaraju, C; Arvinda, H R; Nagappa, Madhu; Sinha, Sanjib; Thangaraj, K

2014-10-01

Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006-2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Successful use of long acting octreotide in two cases with Beckwith-Wiedemann syndrome and severe hypoglycemia.

PubMed

Al-Zubeidi, Hiba; Gottschalk, Michael E; Newfield, Ron S

2014-01-01

Hyperinsulinism associated with Beckwith-Wiedemann syndrome (BWS) can occur in about 50% of cases, causing hypoglycemia of variable severity. Parenteral use of octreotide may be indicated if unresponsive to diazoxide. There is limited data on use of octreotide in BWS. Chart review describing 2 cases with BWS and hypoglycemia treated with long acting Octreotide as a monthly injection. We describe two unrelated females born large for gestational age found to have clinical features consistent with BWS, who developed severe hypoglycemia. Genetic diagnosis of BWS was confirmed. The first patient was born at 37 weeks and developed hypoglycemia shortly after birth. She was initially started on diazoxide but developed pulmonary congestion and was therefore switched to depot octreotide (LAR). She maintained euglycemia with LAR. In the second patient (born at 26-4/7 weeks), onset of hypoglycemia was delayed till 11 weeks of age due to hydrocortisone (indicated hemodynamically) and continuous feeding, and was partially responsive to diazoxide. She was switched to octreotide 4 times daily, treated till at age 18 months. Despite frequent feeds, she required treatment again between ages 4-6.5 years, initially with diazoxide but due to severe hypertrichosis she was switched to LAR with an excellent response. Both patients treated with LAR for over two years achieved euglycemia above 70 mg/dl and had normal height gain, without side effects. Successful treatment of hypoglycemia can be achieved and maintained with LAR in infants and children with BWS who are either resistant or cannot tolerate diazoxide.

[Developmental abnormalities and nevi of the scalp].

PubMed

Behle, V; Hamm, H

2014-12-01

Unusual congenital or early-onset skin lesions on the scalp often pose a diagnostic challenge particularly as the clinical evaluation may be hampered by dense hair growth. Thus, this paper provides a concise review on developmental abnormalities and nevi with exclusive or predominant scalp localization. Aplasia cutis congenita occurs as an isolated finding, in association with genetic syndromes, nevi and anomalies or as a consequence of intrauterine trauma and teratogens. A hairless area with a narrow surrounding rim of hypertrichosis (hair collar sign) may point to occult cranial dysraphism, especially if accompanied by further suggestive signs as port-wine stains, large hemangiomas, dimples, congenital dermoid cysts, and sinuses. Many diverse entities may hide behind cutis verticis gyrata with the primary essential form being rare and representing a diagnosis of exclusion. In contrast to former belief, benign adnexal tumors arise in a nevus sebaceus considerably more often than basal cell carcinomas and other malignant epithelial tumors. Provided that tumor development is not suspected, excision of a nevus sebaceus nevus is indicated primarily for aesthetic-psychosocial reasons. However, surgical treatment is considerably easier in small children. Nevus sebaceus may be a cutaneous marker for several complex syndromes whereas nevus psiloliparus presents almost always in connection with encephalocraniocutaneous lipomatosis. Congenital melanocytic nevi of the scalp tend toward clinical regression, so that surgical intervention in large lesions should be carefully considered. In contrast, the threshold for excision of blue nevi and other conspicuous melanocytic nevi on the scalp should be low, especially since they are difficult to monitor.

Epidemiology of pituitary pars intermedia dysfunction: A systematic literature review of clinical presentation, disease prevalence and risk factors.

PubMed

Ireland, J L; McGowan, C M

2018-05-01

Pituitary pars intermedia dysfunction (PPID) is caused by an age-related degenerative disease of dopaminergic neurones. Despite its importance in equine practice, available information regarding its epidemiology is limited. This systematic review aimed to assess published literature to evaluate available evidence regarding the clinical presentation, prevalence and risk factors for PPID in horses and ponies. Electronic database searches were undertaken using a range of terms, and English language publications published prior to August 2016 were included. Both authors independently reviewed screened papers for inclusion, extracted data, and assessed the quality of reporting using predefined criteria. Data were extracted using modified critically appraised topic data collection forms. Meta-analysis was not undertaken due to marked between-study variations. Following removal of duplicate records, of 358 published papers yielded by the search, 97 abstracts were screened for eligibility and 29 publications meeting inclusion criteria were included in the review. Most studies reviewed were case series or cross-sectional studies, with considerable variation in study populations and PPID case definition. Hypertrichosis and/or other hair coat abnormalities, laminitis and epaxial muscle wastage or muscle atrophy are the most frequently reported clinical signs, with prevalence of these signs increasing with increasing horse age. The most robust prevalence estimates for PPID were 21.2% in horses and ponies aged ≥15 years and 2.9% amongst the general equine population. Findings regarding breed and sex predispositions were equivocal and only increasing age has been identified as a significant risk factor for PPID. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors.

PubMed

Osio, A; Mateus, C; Soria, J-C; Massard, C; Malka, D; Boige, V; Besse, B; Robert, C

2009-09-01

Acute and subacute cutaneous side-effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. Much less is known about the chronic cutaneous effects of these drugs and about their potential psychosocial impact on patients. We performed a retrospective study of patients treated with EGFRIs for more than 6 months. All patients had a detailed dermatological examination. The primary cancer, associated chemotherapies, skin treatment, evolution of skin symptoms and their impact on quality of life (QoL) as evaluated by the Dermatology Life Quality Index (DLQI) were noted. Seven men and nine women were identified. The mean length of EGFRI treatment was 10 months (range 6-27). At the time of examination, all patients (100%) had cutaneous side-effects. Grade I or II folliculitis was found in 37.5% of the patients. Additional skin manifestations were xerosis (100%), mucositis (69%), hair abnormalities (87.5%), eyelash trichomegaly (62.5%), facial hypertrichosis (56%), painful paronychia (56%) and onycholysis (44%). Dose reduction or EGFRI discontinuation for skin toxicity were needed in six patients (37.5%). DLQI evaluation showed a moderate to strong impact on QoL in four patients (25%). Cutaneous side-effects are found in 100% of patients treated with EGFRIs for more than 6 months and have a significant effect on patients' QoL. The clinical spectrum of skin manifestation varies over time. As the use of EGFRIs rapidly increases, it is critical for us to improve our knowledge in the understanding and managment of these skin manifestations.

Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: an update.

PubMed

Nakamura, Motonobu; Schneider, Marlon R; Schmidt-Ullrich, Ruth; Paus, Ralf

2013-01-01

Human hair disorders comprise a number of different types of alopecia, atrichia, hypotrichosis, distinct hair shaft disorders as well as hirsutism and hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias) to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number of spontaneous mouse mutants and genetically engineered mice develop abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft formation, whose analysis has proven invaluable to define the molecular regulation of hair growth, ranging from hair follicle development, and cycling to hair shaft formation and stem cell biology. Also, the accumulating reports on hair phenotypes of mouse strains provide important pointers to better understand the molecular mechanisms underlying human hair growth disorders. Since numerous new mouse mutants with a hair phenotype have been reported since the publication of our earlier review on this matter a decade ago, we present here an updated, tabulated mini-review. The updated annotated tables list a wide selection of mouse mutants with hair growth abnormalities, classified into four categories: Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3) structure, and (4) mutations that induce extrafollicular events (for example immune system defects) resulting in secondary hair growth abnormalities. This synthesis is intended to provide a useful source of reference when studying the molecular controls of hair follicle growth and differentiation, and whenever the hair phenotypes of a newly generated mouse mutant need to be compared with existing ones. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features

PubMed Central

Low, Karen J; Ansari, Morad; Abou Jamra, Rami; Clarke, Angus; El Chehadeh, Salima; FitzPatrick, David R; Greenslade, Mark; Henderson, Alex; Hurst, Jane; Keller, Kory; Kuentz, Paul; Prescott, Trine; Roessler, Franziska; Selmer, Kaja K; Schneider, Michael C; Stewart, Fiona; Tatton-Brown, Katrina; Thevenon, Julien; Vigeland, Magnus D; Vogt, Julie; Willems, Marjolaine; Zonana, Jonathan; Study, D D D; Smithson, Sarah F

2017-01-01

PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function. PMID:28327570

The neuropeptide galanin is a novel inhibitor of human hair growth.

PubMed

Holub, B S; Kloepper, J E; Tóth, B I; Bíro, T; Kofler, B; Paus, R

2012-07-01

Galanin is a trophic factor of the central and peripheral nervous system that shows widespread distribution in human skin. However, the exact localization and the role of galanin in the hair follicle (HF) remain to be clarified. To characterize galanin expression in human scalp HFs and to examine the effects of galanin on normal human scalp HF growth in organ culture. Immunohistochemistry was performed on cryosections of human female scalp skin. Anagen HFs were microdissected and cultured up to 9 days and treated with 100 nmol L(-1) galanin. Staining for Ki-67, TUNEL and Masson-Fontana were used to analyse proliferation, apoptosis and hair cycle staging of the HFs. Functional effects of galanin were tested in serum-free HF organ culture. Galanin-like immunoreactivity was detected in the outer root sheath (ORS) and inner root sheath. Additionally, galanin mRNA was detected in ORS keratinocytes and all HF samples tested. Galanin receptor transcripts (GalR2, GalR3) were also detected in selected samples. Galanin reduced proliferation of hair matrix keratinocytes in situ compared with vehicle-treated controls, shortened the hair growth phase (anagen) in vitro and reduced hair shaft elongation. This was accompanied by the premature development of a catagen-like morphology of galanin-treated HFs. We present the first evidence that human HFs are both a source and a functionally relevant target of galanin. Due to its hair growth-inhibitory properties in vitro, galanin application deserves further exploration as a potential new treatment strategy for unwanted hair growth (hirsutism, hypertrichosis). © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses.

PubMed

Innerå, Marie; Petersen, Annette D; Desjardins, Danielle R; Steficek, Barbara A; Rosser, Edmund J; Schott, Harold C

2013-02-01

Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. The aim of this study was to compare hair follicle stages in PPID-affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID-affected horses after 6 months of treatment with pergolide mesylate with those of control horses. Eight PPID-affected horses and four normal, age-matched, control horses. Skin biopsies were collected from the neck and rump of PPID-affected and control horses. A diagnosis of PPID was established based on hair coat changes and supportive overnight dexamethasone suppression test results. Skin biopsies were repeated after 6 months of treatment with pergolide. The number of hair follicles in anagen (A) or telogen (T) was counted for each skin biopsy using transverse sections. Pretreatment biopsies had a greater percentage of A follicles (neck 96%, rump 95%) and a lower percentage of T follicles (neck 4%, rump 5%) in PPID-affected horses than in control horses (A, neck 15%, rump 25%; and T, neck 85%, rump 75%). After treatment with pergolide, all PPID-affected horses had improved shedding, and the percentages of A follicles (neck 69%, rump 70%) and T follicles (neck 31%, rump 30%) were not different from untreated control horses (A, neck 68%, rump 82%; and T, neck 32%, rump 18%). These findings document that excessive hair growth (hypertrichosis) in PPID-affected horses is due to persistence of hair follicles in A. Furthermore, treatment with pergolide improved shedding and reduced the percentage of A follicles in PPID-affected horses. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil.

PubMed

Li, M; Marubayashi, A; Nakaya, Y; Fukui, K; Arase, S

2001-12-01

The mechanism by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hypertrichosis remains to be elucidated. Minoxidil has been reported to stimulate the production of vascular endothelial growth factor, a possible promoter of hair growth, in cultured dermal papilla cells. The mechanism of production of vascular endothelial growth factor remains unclear, however. We hypothesize that adenosine serves as a mediator of vascular endothelial growth factor production. Minoxidil-induced increases in levels of intracellular Ca(2+) and vascular endothelial growth factor production in cultured dermal papilla cells were found to be inhibited by 8-sulfophenyl theophylline, a specific antagonist for adenosine receptors, suggesting that dermal papilla cells possess adenosine receptors and sulfonylurea receptors, the latter of which is a well-known target receptor for adenosine-triphosphate-sensitive potassium channel openers. The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis. In order to determine which of the adenosine receptor subtypes contribute to minoxidil-induced hair growth, the effects of subtype-specific antagonists for adenosine receptors were investigated. Significant inhibition in increase in intracellular calcium level by minoxidil or adenosine was observed as the result of pretreatment with 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A1 receptor, but not by 3,7-dimethyl-1-propargyl-xanthine, an antagonist for adenosine A2 receptor, whereas vascular endothelial growth factor production was blocked by both adenosine A1 and A2 receptor antagonists. These results indicate that the effect of minoxidil is mediated by adenosine, which triggers intracellular signal transduction via both adenosine A1 and A2 receptors, and that the expression of sulfonylurea receptor 2B in

Lung transplantation for cystic fibrosis.

PubMed

Coloni, G F; Venuta, F; Ciccone, A M; Rendina, E A; De Giacomo, T; Filice, M J; Diso, D; Anile, M; Andreetti, C; Aratari, M T; Mercadante, E; Moretti, M; Ibrahim, M

2004-04-01

Lung transplantation is a robust therapeutic option to treat patients with cystic fibrosis. Since 1996, 109 patients with cystic fibrosis were accepted onto our waiting list with 58 bilateral sequential lung transplants performed in 56 patients and two patients retransplanted for obliterative bronchiolitis syndrome. Preoperative mean FEV(1) was 0.64 L/s, mean PaO(2) with supplemental oxygen was 56 mm Hg, and the mean 6-minute walking test was 320 m. Transplantation was performed through a "clam shell incision" in the first 29 patients and via bilateral anterolateral thoracotomies without sternal division in the remaining patients. Cardiopulmonary bypass was required in 14 patients. In 21 patients the donor lungs had to be trimmed by wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Eleven patients were extubated in the operating room immediately after the procedure. Hospital mortality of 13.8% was related to infection (n = 5), primary graft failure (n = 2), and myocardial infarction (n = 1). Acute rejection episodes occurred 1.6 times per patient/year; lower respiratory tract infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV(1) increased to 82% at 1 year after operation. The 5-year survival rate was 61%. A cyclosporine-based immunosuppressive regimen was initially employed in all patients; 24 were subsequently switched to tacrolimus because of central nervous system toxicity, cyclosporine-related myopathy, or renal failure, obliterative bronchiolitis syndrome, gingival hyperplasia, or hypertrichosis. Ten patients were subsequently switched to sirolimus. Freedom from bronchiolitis obliterans at 5 years was 60%. Our results confirm that bilateral sequential lung transplantation is a robust therapeutic option for patients with cystic fibrosis.

Fatal toxic epidermal necrolysis associated with minoxidil.

PubMed

Karaoui, Lamis R; Chahine-Chakhtoura, Corinne

2009-04-01

Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27-31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this

Cushing's syndrome due to ectopic production of corticotropin-releasing hormone in an infant with ganglioneuroblastoma.

PubMed

Zangeneh, Farhad; Young, William F; Lloyd, Ricardo V; Chiang, Myra; Kurczynski, Elizabeth; Zangeneh, Fereydoun

2003-01-01

To report the first recognized case of Cushing's syndrome due to a corticotropin-releasing hormone (CRH)-secreting ganglioneuroblastoma, which was found in an 18-month-old boy with hypertensive encephalopathy. The clinical, biochemical, and immunohistochemical characteristics of this rare syndrome are described, and the relevant literature is reviewed. An 18-month-old boy with a history of recent weight gain was admitted because of sudden onset of right fixed esotropia and left facial palsy after episodes of emesis. Magnetic resonance imaging showed old left frontal lobe and right hypothalamic infarcts. The patient had generalized obesity, decelerated linear growth, hypertrichosis, hypertension (144/103 mm Hg), hypokalemia, and proteinuria. The 24-hour urinary excretion of free cortisol, catecholamines, and metanephrines was increased. The serum cortisol concentration after a 1-mg overnight dexamethasone suppression test (DST) was 53.7 mg/dL (normal, <5). The serum adrenocorticotropic hormone (ACTH) concentration was 7 pg/mL (normal, 10 to 60), and the CRH level was 439 pg/mL (normal, 24 to 40). An overnight high-dose DST (8 mg) failed to suppress serum cortisol; however, both cortisol and ACTH were responsive to ovine CRH stimulation. Despite discordant dynamic endocrine testing and negative somatostatin receptor scintigraphy, computed tomography showed a right 3.6- by 3.0-cm extra-adrenal retroperitoneal mass with central calcification extending 7 cm cephalocaudally. The patient underwent exploratory laparotomy, followed by chemotherapy. Findings on light microscopic and immunohistochemical examination of the retroperitoneal mass were consistent with a ganglioneuroblastoma that expressed CRH, pro-opiomelanocortin, and ACTH. The evaluation of Cushing's syndrome is one of the most complex endocrine challenges. In this case, it was due to ectopic production of CRH by a ganglioneuroblastoma. Because most CRH-producing tumors also secrete ACTH, the ectopic production

Treatment of chronic telogen effluvium with oral minoxidil: A retrospective study.

PubMed

Perera, Eshini; Sinclair, Rodney

2017-01-01

Background : Chronic telogen effluvium (CTE) may be primary or secondary to various causes, including drug reaction, nutritional deficiency and female pattern hair loss (FPHL).  Oral minoxidil stimulates hair growth, and topical minoxidil is used in the treatment of FPHL and male androgenetic alopecia. minoxidil has not been used to treat CTE. This study aimed to assess the treatment of CTE with once daily oral minoxidil. Methods : Women with a diagnosis of CTE based on >6 month history of increased telogen hair shedding, no visible mid frontal scalp hair loss (Sinclair stage 1) and no hair follicle miniaturization on scalp biopsy were treated with once daily oral minoxidil.  Hair shedding scores (HSS) at baseline, 6 and 12 months were analysed using the Wilcoxon rank sum test for pair-wise comparisons. Results : Thirty-six women were treated with oral minoxidil (range, 0.25-2.5 mg) daily for 6 months.  Mean age was 46.9 years (range 20-83), HSS at baseline was 5.64, and duration of diagnosis was 6.55 years (range 1-27).  There was a reduction in mean HSS scores from baseline to 6 months of 1.7 (p<0.001) and baseline to 12 months of 2.58 (p<0.001). Five women who described trichodynia at baseline, noted improvement or resolution within 3 months.  Mean change in blood pressure was minus 0.5 mmHg systolic and plus 2.1 mmHg diastolic.  Two patients developed transient postural dizziness that resolved with continued treatment.  One patient developed ankle oedema.  Thirteen women developed facial hypertrichosis.  For 6 patients this was mild and did not require treatment; 4 had waxing of their upper lip or forehead; 3 had laser hair removal.  No patients developed any haematological abnormality.  All 36 women completed 12 months of treatment. Conclusions : Once daily oral minoxidil appears to reduce hair shedding in CTE.  Placebo controlled studies are recommended to further assess this response.

A Phase III, Multicenter, Parallel-Design Clinical Trial to Compare the Efficacy and Safety of 5% Minoxidil Foam Versus Vehicle in Women With Female Pattern Hair Loss.

PubMed

Bergfeld, Wilma; Washenik, Ken; Callender, Valerie; Zhang, Paul; Quiza, Carlos; Doshi, Uday; Blume-Peytavi, Ulrike

2016-07-01

BACKGROUND Female pattern hair loss (FPHL) is a common hair disorder that affects millions of women. A new 5% minoxidil topical foam (MTF) formulation, which does not contain propylene glycol, has been developed.
To compare the efficacy and safety of once-daily 5% MTF with vehicle foam for the treatment of FPHL.
This was a Phase III, randomized, double-blind, vehicle-controlled, parallel-group, international multicenter trial (17 sites) in women aged at least 18 years with FPHL (grade D3 to D6 on the Savin Density Scale), treated once daily with 5% MTF or vehicle foam for 24 weeks. The co-primary efficacy endpoints were the change from baseline at week 24 in target area hair count (TAHC) and subject assessment of scalp coverage. Also evaluated were TAHC at week 12, expert panel review of hair regrowth at week 24, and change from baseline in total unit area density (TUAD, sum of hair diameters/cm²) at weeks 12 and 24.
A total of 404 women were enrolled. At 12 and 24 weeks, 5% MTF treatment resulted in regrowth of 10.9 hairs/cm² and 9.1 hairs/cm² more than vehicle foam, respectively (both P<.0001). Improved scalp coverage at week 24 was observed by both subject self-assessment (0.69-point improvement over vehicle foam; P<.0001) and expert panel review (0.36-point improvement over the vehicle foam; P<.0001). TUAD increased by 658 μm/cm² and 644 μm/cm² more with 5% MTF than with vehicle foam at weeks 12 and 24, respectively (both P<.0001). MTF was well tolerated. A low incidence of scalp irritation and facial hypertrichosis was observed, with no clinically significant differences between groups.
Five percent MTF once daily for 24 weeks was well tolerated and promoted hair regrowth in women with FPHL, resulting in improved scalp coverage and increased hair density compared with vehicle foam. ClinicalTrials.gov identifier: nCT01226459

Prospective Observational Post-Marketing Study of Tafluprost for Glaucoma and Ocular Hypertension: Effectiveness and Treatment Persistence.

PubMed

Kuwayama, Yasuaki; Hashimoto, Masako; Kakegawa, Reiko; Nomura, Akio; Shimada, Fumiki

2017-06-01

The aim of this study was to investigate the long-term intraocular pressure (IOP)-lowering effect and safety of tafluprost, a prostaglandin analogue, in actual clinical practice and to determine persistency of tafluprost as an indicator of its benefit-risk balance. This was a large-scale, post-marketing, multicenter, non-interventional, open-label, long-term study. Patients with glaucoma or ocular hypertension who initiated tafluprost treatment were registered and prospectively observed over a 2-year period in the real-world setting in Japan. Long-term IOP and safety data were collected. Of the 4502 patients registered from 553 medical institutions, 4265 patients were analyzed. The majority of patients had normal-tension glaucoma (44.4%) and primary open-angle glaucoma (37.8%), and patients with ocular hypertension constituted 7.0%. Treatment patterns with tafluprost during the study period were as follows: naïve monotherapy (48.1%), switching monotherapy (18.4%), and concomitant therapy (33.5%). In all patients analyzed, mean IOP was significantly reduced from 18.6 ± 5.9 mmHg (month 0) to 15 mmHg or below throughout the 2-year observation period after initiation of tafluprost. Significant IOP-lowering effects were shown in various treatment patterns and disease types. Adverse reactions were observed in 795 patients (18.64%). Major adverse reactions included eyelid pigmentation, ocular hyperemia, eyelash changes, eyelid hypertrichosis, and iris hyperpigmentation. Kaplan-Meier curves showed that 84.6% and 76.1% of patients were persistent on tafluprost for 1 and 2 years, respectively, when discontinuation due to insufficient efficacy or adverse events was defined as a treatment failure event. Furthermore, among treatment-naïve patients (n = 2304), the persistency rates on tafluprost monotherapy were 77.0% for 1 year and 67.0% for 2 years. Tafluprost showed significant long-term IOP-lowering effects regardless of treatment patterns or diagnosis, with

Mitchell's influence on European studies of peripheral nerve injuries during World War I.

PubMed

Koehler, Peter J; Lanska, Douglas J

2004-12-01

Describe the influence of S. Weir Mitchell's (1829-1914) work, and in particular his ideas on causalgia, on European physicians who treated peripheral nerve injuries during World War I (WWI). During the American Civil War (1861-1865), Mitchell studied peripheral nerve injuries with colleagues George Read Morehouse and William Williams Keen. Three monographs resulted from this work. All were important landmarks in the evolution of knowledge of peripheral nerve injuries. A subsequent occasion to improve knowledge came in WWI. The most important European monographs or series on peripheral nerve injuries from WWI were studied with special interest in references to causalgia and Mitchell's works on peripheral nerve injuries. We included works by Tinel, Athanassio-Benisty, Purves-Stewart & Evans and Carter, Foerster and Oppenheim. Tinel and Athanassio-Benisty provided the most detailed information on peripheral nerve injuries and causalgia and often referred to Mitchell. Both mentioned a possible sympathetic origin. Athanassio-Benisty described tremor and other movement disorders in relation to causalgia. Purves-Stewart and Evans mentioned Mitchell and causalgia in the second edition of their book. They advocated the term "thermalgia." Carter, who had access to data of many cases, concentrated his work on causalgia, referring to Mitchell. Foerster provided data of a great number of peripheral nerve injuries, but did not refer to Mitchell. However, he described the symptoms of causalgia cursorily, applying the term Reflexschmerz (reflexpain). Oppenheim was particularly interested in muscle innervation and referred to Mitchell with respect to hypertrichosis and glossy skin. Oppenheim did not use the term causalgia, although he described the syndrome in some of his patients. It wasn't until around 1920 that German physicians devoted significant attention to causalgia and began using the term. Knowledge of peripheral nerve injuries was greatly advanced during and after WWI

Choice, Transparency, Coordination, and Quality Among Direct-to-Consumer Telemedicine Websites and Apps Treating Skin Disease.

PubMed

Resneck, Jack S; Abrouk, Michael; Steuer, Meredith; Tam, Andrew; Yen, Adam; Lee, Ivy; Kovarik, Carrie L; Edison, Karen E

2016-07-01

Evidence supports use of teleconsultation for improving patient access to dermatology. However, little is known about the quality of rapidly expanding direct-to-consumer (DTC) telemedicine websites and smartphone apps diagnosing and treating skin disease. To assess the performance of DTC teledermatology services. Simulated patients submitted a series of structured dermatologic cases with photographs, including neoplastic, inflammatory, and infectious conditions, using regional and national DTC telemedicine websites and smartphone apps offering services to California residents. Choice of clinician, transparency of credentials, clinician location, demographic and medical data requested, diagnoses given, treatments recommended or prescribed, adverse effects discussed, care coordination. We received responses for 62 clinical encounters from 16 DTC telemedicine websites from February 4 to March 11, 2016. None asked for identification or raised concerns about pseudonym use or falsified photographs. During most encounters (42 [68%]), patients were assigned a clinician without any choice. Only 16 (26%) disclosed information about clinician licensure, and some used internationally based physicians without California licenses. Few collected the name of an existing primary care physician (14 [23%]) or offered to send records (6 [10%]). A diagnosis or likely diagnosis was proffered in 48 encounters (77%). Prescription medications were ordered in 31 of 48 diagnosed cases (65%), and relevant adverse effects or pregnancy risks were disclosed in a minority (10 of 31 [32%] and 6 of 14 [43%], respectively). Websites made several correct diagnoses in clinical scenarios where photographs alone were adequate, but when basic additional history elements (eg, fever, hypertrichosis, oligomenorrhea) were important, they regularly failed to ask simple relevant questions and diagnostic performance was poor. Major diagnoses were repeatedly missed, including secondary syphilis, eczema

[A case of anaphylactoid shock occurring immediately after the initiation of second intravenous administration of high-dose immunoglobulin (IVIg) in a patient with Crow-Fukase syndrome].

PubMed

Takahashi, Teruyuki; Ono, Shin-ichi; Ogawa, Katuhiko; Tamura, Masato; Mizutani, Tomohiko

2003-06-01

We report a case of anaphylactoid shock occurring immediately after the initiation of second intravenous administration of high-dose immunoglobulin (IVIg) in a patient with Crow-Fukase syndrome. The patient was a 57-year-old woman, who was admitted to our hospital because of numbness and muscle weakness in the four extremities, difficulty in walking, and foot edema. On admission, her skin was dry and rough, and also showing scattered pigmentation, small hemangiomas, and hypertrichosis in both legs. She had distal dominant muscle weakness, more prominent in her legs, and was not able to walk. Deep tendon reflexes in her four extremities were markedly diminished or absent. She had a glove and stocking type of paresthesia, severe impairment of vibration, and absence of joint position sensation in her four extremities. On laboratory data, serum vascular endothelial growth factor (VEGF) was markedly elevated to 5,184 pg/ml (normal: below 220 pg/ml). Cerebrospinal fluid examination revealed cell counts of 2/microliter and protein level of 114 mg/dl. Abdominal echo showed marked hepatosplenomegaly. On peripheral nerve conduction study, both motor and sensory conduction velocity were undetectable in her legs. We diagnosed her condition as Crow-Fukase syndrome, and started IVIg of polyethyleneglycol-treated gamma-globulin (PEG-glob) at 400 mg/kg/day for 5 consecutive days for polyneuropathy. Since the first IVIg mildly improved muscle weakness, we tried the second IVIg of PEG-glob. However, immediately after the initiation of second IVIg of PEG-glob, she developed hypotention, dyspnea, cold sweating, cyanosis, and became lethargic. We immediately stopped IVIg and started first-aid treatment with epinephrine and corticosteroid for these symptoms. This treatment was successful and the patient fully recovered without any sequelae. Since serum IgE level remained unchanged and lymphocyte stimulation test (LST) was positive against the same rot number of PEG-glob, we diagnosed

Unicameral bone cyst: radiographic assessment of venous outflow by cystography as a prognostic index.

PubMed

Ramirez, Ana; Abril, Juan Carlos; Touza, Alberto

2012-11-01

The aim of this study was to determine the benefits of cystography in the management of a simple bone cyst, its implication in the final result of the treatment after corticoid intracystic injections, and the presence of secondary effects. We retrospectively reviewed 42 patients diagnosed with a simple bone cyst. Cystography was performed before the corticoid injection. The presence or absence of loculation intracyst and the existence and number of venous outflows were determined. According to the venous drainage, cysts were classified as type 0 when a venous outflow did not exist and as type 1 when there was a rapid venous outflow (<3 min). The treatment protocol included a maximum of three corticoid injections at an interval of 6 months. Healing of the cyst was determined on the basis of Neer's criteria. Secondary effects and surgical complications were assessed. Cystography studies showed a unicameral bone cyst with absent loculation in 16 cases (37.3%), whereas the lesion showed multiloculation in 26 cases (62.7%). There was no statistical difference between loculation intracyst (present or absent) and the final outcomes of the 42 cysts treated with a steroid injection (P=0.9). Cystography showed a negative venogram in 10 cases (23.8%), whereas the cysts showed a rapid venous outflow in 32 cases (76.2%). On the basis of Neer's classification, all patients with a negative venogram achieved complete healing of the cyst. Patients with a rapid venous outflow achieved complete healing in 14 cases (Neer I). In two patients, the healing was incomplete at the end of the follow-up period (Neer IV). In most cases (21 cysts), healing was partial (Neer II). Five patients showed a recurrence after initial healing of the cyst (Neer III) (P<0.05). The number or the size of veins did not affect healing of a bone cyst (P=0.6). Two patients with a rapid venous outflow showed a generalized hypertrichosis after the first injection of corticosteroids. Sex and age at the initiation

Topical medication instillation techniques for glaucoma

PubMed Central

Xu, Li; Wang, Xuemei; Wu, Meijing

2017-01-01

(122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We also identified two ongoing trials. Both included trials used a within-person design and administered prostaglandin monotherapy for glaucoma or ocular hypertension. Because the trials evaluated different instillation techniques and assessed different outcomes, we performed no meta-analysis. One trial, conducted in the US, evaluated the effect of eyelid closure (one and three minutes) versus no eyelid closure on lowering IOP. At one to two weeks' follow-up, reduction in IOP was similar in the eyelid closure group and the no eyelid closure group (mean difference (MD) -0.33 mmHg, 95% confidence interval (CI) -0.8 to 1.5; 51 participants; moderate-certainty evidence). The second trial, conducted in Italy, evaluated the effect of using an absorbent cloth to wipe excess fluid after instillation (fluid removal) versus not using an absorbent cloth (no removal) on reducing dermatologic adverse events. At four months' follow-up, eyelashes were shorter among eyes in the fluid removal group compared with the no fluid removal group (MD -1.70 mm, 95% CI -3.46 to 0.06; 10 participants; low-certainty evidence). Fewer eyes showed skin hyperpigmentation in the eyelid region towards the nose in the fluid removal group compared with the no removal group (RR 0.07, 95% CI 0.01 to 0.84; 10 participants; low-certainty evidence); however, the difference was uncertain in the eyelid region towards the temples (RR 0.44, 95% CI 0.07 to 2.66; 10 participants; low-certainty evidence). The effect hypertrichosis (excessive hair growth) was uncertain between groups (RR 1.00, 95% CI 0.17 to 5.98; 10 participants; low-certainty evidence). Neither trial reported other outcomes specified for this review, including the proportion of participants with IOP less than 21 mmHg; participant-reported outcomes related to the ease, convenience, and comfort of instillation techniques; physiologic measurements of systemic