Advances of Congenital Alopecia/Hypotrichosis in Genetics Research / 罕见病研究

Congenital alopecia/hypotrichosis is a rare group of monogenic genetic hair disorders characterized by congenital limited or diffuse hair loss and scarcity, without any effective treatment. Genetic testing to identify the causative gene mutation is the gold standard for confirming the diagnosis of this group of disorders. Because of the heterogeneity in clinical features and genetic pattern of this group of diseases, it is very easy to misdiagnose and mistreat them as diffuse baldness or androgenic alopecia and other acquired alopecia, so clinicians should improve their understanding of this group of diseases. With the continuous development of molecular biology techniques in recent years, a variety of causative genes for congenital alopecia/hypotrichosis have been identified so far, and the pathogenesis of some of these genes and their corresponding subtypes have been clarified. In this paper, we reviewed the clinical manifestations and genetic research progress of non-syndromic congenital alopecia/ hypotrichosis, in order to facilitate clinicians' comprehensive understanding of these rare hair diseases and improve clinical diagnosis and treatment.

A novel mutation in the LSS gene caused congenital hypotrichosis type 14 in a Chinese family / 中华皮肤科杂志

Objective:To report a patient with congenital hypotrichosis 14 complicated by hypergonadotropic hypogonadism, and to analyze LSS gene mutations in his family.Methods:Peripheral blood samples were collected from the proband and his parents with normal phenotypes, and genomic DNA was extracted from these samples. Second-generation sequencing was performed to screen suspected mutations among hereditary hair disorder-associated genes. Possible causative genes were identified from the screened suspected variants based on clinical phenotypes, and verified using Sanger sequencing. The identified variants were also verified in healthy controls, and searched in the Human Gene Mutation Database, 1000 Genomes Project database, and ExAC database.Results:The patient harbored a homozygous missense mutation c.812T>C (p.Ile271Thr) in exon 8 of the LSS gene, and his parents were the mutation carriers. The variant was not present in healthy controls and databases.Conclusion:The homozygous mutation c.812T>C in the LSS gene may be the causative mutation for congenital hypotrichosis 14 in this family, which was a novel mutation that had not been reported before.

Moniletrix of the scalp from almost normal aspect to total alopecia: variable intrafamilial expressiveness

Abstract Monilethrix is a rare defect of the hair shaft, with most cases showing an autosomal dominant pattern of inheritance and variable clinical expression. It is characterized by hypotrichosis secondary to hair fragility. The diagnosis is made through trichoscopy, detecting typical findings such as periodic narrowing at regular intervals, giving the hair the appearance of beads in a rosary. This article reports the case of six members of a family diagnosed with monilethrix with alopecia of varying degrees.

Prosthetic Rehabilitation in a Child with Hereditary Ectodermal Dysplasia

Hereditary ectodermal dysplasia is a disease linked to the X recessive chromosome that affects the development of tissues derived from the ectoderm. The main clinical manifestations include hypohidrosis (inability to sweat), hypotrichosis (sparse hair) and hypodontia (lack teeth). This work presents a clinical case of a 6-year old male child who had been diagnosed with hereditary ectodermal dysplasia. The treatment consisted of the fabrication of a mandibular and maxillary complete denture to improve his esthetic, functional and psychological conditions.

Description of clinical aspects and microscopy of the hair shaft of a carrier of familial monilethrix / Descrição dos aspectos clínicos e da microscopia da haste capilar de um portador de monilétrix familiar

ABSTRACT Monilethrix is a genetic condition that affects the hair shaft. We describe a family with this disease, focusing on its clinical aspects and microscopic hair characteristics. The patient was a 10-year-old female with history of hypotrichosis. In addition to diffuse alopecia, there was brittle hair, with ruptures in the hair shaft at different levels. The hair had a nodular appearance at naked eye. Other family members had the same symptoms, what indicates an autosomal dominant pattern of inheritance. Microscopic analysis revealed capillary fibers with areas of elliptical nodular appearance interspersed with regions of dystrophic constriction.

RESUMO A monilétrix é uma condição genética que acomete a haste capilar. Descrevemos uma família com essa doença, enfocando seus aspectos clínicos e as características microscópicas do cabelo. A paciente era do sexo feminino, 10 anos de idade, e apresentava história de hipotricose. Além da alopecia difusa, notava-se um cabelo quebradiço, com rupturas na haste capilar em diferentes níveis. Os cabelos possuíam um aspecto nodular a olho nu. Outros membros da família apresentavam os mesmos sintomas, o que indica um padrão de herança autossômica dominante. A análise microscópica revelou fibras capilares com áreas de aparência nodular elíptica, intercaladas por regiões de constrição distrófica.

Do you know this syndrome? Clouston syndrome

Abstract Ectodermal dysplasias are conditions that present primary defects in two or more tissues of ectodermal origin and can be classified as hypohidrotic and hidrotic. Hidrotic ectodermal dysplasia or Clouston syndrome is an autosomal dominant genodermatosis and appears as a triad of clinical findings: palmoplantar keratoderma, nail dystrophy, and hypotrichosis. The hair is sparse and brittle. The nails become thickened and dystrophic, which is an essential characteristic of the syndrome. The diagnosis is made based on clinical findings. This study reports a case of a patient who began with changes in hair, nails and palmoplantar keratoderma in early childhood.

Hypotrichosis with juvenile macular dystrophy: a case report with molecular study / Hipotricose com distrofia macular juvenil: relato de caso com estudo molecular

ABSTRACT Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by sparse scalp hair caused by hair follicle abnormalities as well as progressive retinal degeneration leading to blindness in the second or third decade of life. It is associated with mutations of the cadherin 3 (CDH3) gene, which result in abnormal expression of P-cadherin. Mutations in CDH3 are related to ectodermal dysplasia, ectrodactyly, and macular dystrophy. In this report, we describe an 11-year-old Iranian boy born with a missing left index fingernail and sparse scalp hair who later displayed macular pigmentary changes. Genetic testing of the CDH3 gene revealed a homozygous gene variant at exon 6 (640A>T). This novel in-frame mutation converts a lysine to a premature stop codon, altering synthesis of P-cadherin on chromosome 16q22.

RESUMO Hipotricose com distrofia macular juvenil (HDMJ) é uma doença autossômica recessiva rara caracterizada por rarefação capilar por alteração nos folículos pilosos e degeneracão progressiva da retina levando a cegueira na segunda e terceira década de vida. Associada a mutações no gene CDH3, resultando em expressão anormal de P-caderina. Mutações no gene CDH3 estão relacionados à displasia ectodérmica, ectrodactilia e distrofia macular. Neste relato descrevemos um menino Iraniano de 11 anos de idade, com ausência da unha na mão esquerda e rarefação capilar desde o nascimento, e que posteriormente apresentou alterações pigmentares maculares. Teste genético do gene CDH3 revelou uma variação homozigótica no exon 6 (640A>T). Essa mutação in-frame troca uma lisina por um codon de parada prematura, alterando a síntese da proteína P-caderina no cromossomo 16q22.

Mutation analysis of causative genes in a case of congenital hypotrichosis / 中华皮肤科杂志

Objective To identify the genetic cause of a case of congenital hypotrichosis by a nextgeneration sequencing technology.Methods A 9-year and 3-month-old girl presented with few villous hairs at birth,which grew slowly.Skin examination showed sparse,thin,soft,woolly and light-yellow hairs,small amount of hairs on the top of the head and a less amount of hairs around the head,hairline recession and broadened forehead.No abnormality was found by ophthalmic examination.No similar aberrant phenotype was observed in the patient's parents or her younger sister.Her parents were non-consanguineous marriage.Peripheral venous blood samples were obtained from the patient,her mother and younger sister.Genomic DNA was extracted and then analyzed by a next-generation sequencing technology.The suspected pathogenic mutations were validated by Sanger sequencing and subjected to bioinformatics analysis.Results Two mutations were identified in the CDH3 gene in the patient,including a c.1057G ＞ T (p.D353Y) heterozygous mutation in exon 5 and a c.1767delC (p.I589Ifs) heterozygous mutation in exon 10.They were both novel mutations,and their pathogenicity was predicted by softwares.Sanger sequencing indicated that the c.1057G ＞ T (p.D353Y) heterozygous mutation was inherited from the patient's mother,and gene transfer analysis revealed that the c.1767delC (p.I589Ifs) heterozygous mutation was inherited from the patient's father.Conclusion The c.1057G ＞ T (p.D353Y) and c.1767delC (p.I589Ifs)heterozygous mutations may cause hypotrichosis and juvenile macular dystrophy in the patient,so careful observation and comprehensive ophthalmic examination should be performed on time for early diagnosis and treatment of eye symptoms.

Displasia ectodérmica: Un reporte de caso

La displasia ectodérmica (DE) es un trastorno genético que se caracteriza por alteraciones que afectan las estructuras derivadas del ectodermo; usualmente el síndrome presenta hipohidrosis, hipotricosis e hipodoncia, siendo esta última una manifestación importante para los profesionales en odontología. Se presenta el caso de un paciente que acude a consulta odontológica y en el que se identificaron defectos del ectodermo como cabello fino, escaso y alteraciones en la calidad del esmalte dental que sugieren la presencia de DE; además, se realizó una comparación con los tipos de DE más comunes.

Ectodermal Dysplasia (ED) is a genetic disorder characterized by alterations affecting the derived ectoderm structures; the syndrome usually presents hypohidrosis, hypotrichosis and hypodontia, the latter being a fairly significant event for dentists. This case report aimed to show a patient who went to a dentistry appointment and where ectodermal defects such as poor thin hair and enamel quality alterations suggested an ED case; also a comparison of ED types was done.

Clouston Syndrome: 25-year follow-up of a patient

Abstract: Clouston syndrome is a rare genodermatosis that affects skin and annexes. It is a form of ectodermal dysplasia characterized by generalized hypotrichosis, palmoplantar hyperkeratosis and nail dystrophy. This paper reports a 25-year follow-up of a patient with Clouston syndrome, from childhood to adulthood, monitoring diagnosis and clinical course of the disease.

Síndrome Bazex-Dupré-Christol: serie de casos / Bazex-Dupré-Christol syndrome: Case series

El síndrome de Bazex-Dupré-Christol es una genodermatosis ligada al cromosoma X, la cual se caracteriza por presentar hipotricosis congènita, hipohidrosis, atrofodermia folicular, múltiples quistes de millium y carcinomas basocelulares. Presentamos a una niña y su familia con este síndrome. La paciente y sus hermanos de 5 meses de edad y de 17 años de edad presentaban múltiples quistes de millium e hipotricosis de las cejas y el cuero cabelludo. Su hermano de 8 años presentaba quistes de millium y atrofodermia folicular. Su madre presentaba hipohidrosis, hipotricosis congènita del cuero cabelludo y las cejas, así como también una lesión tumoral en la región paranasal derecha compatible con carcinoma basocelular. Destacamos la importancia del diagnóstico y del seguimiento clínico de estos niños por la posibilidad de desarrollar carcinomas basocelulares.

Bazex-Dupré-Christol syndrome is an X-linked dominantly inherited disorder characterized by congenital hypotrichosis, hypohidrosis, follicular atrophoderma, multiple milia and basal cell carcinomas. We present a girl and her family with this syndrome. Our patient, her 5 month old brother and her 17 year old brother had multiple milia and scalp and eyebrows hypotrichosis. Her 8 year old brother had multiple milia and follicular atrophoderma. Her mother had hypohidrosis and congenital scalp and eyebrows hypotrichosis, as well as a right paranasal lesion suggestive of basal cell carcinoma. We emphasize the importance of precise diagnosis and clinical follow up of these patients due to the possibility of developing basal cell carcinomas.

Monilethrix: a typical case report with microscopic and dermatoscopic findings

Monilethrix is a rare hereditary condition generally considered to be an autosomal dominant disorder with variable penetrance. A case of a 6-year-old girl without a familial background for this disease is reported. The diagnosis was made by optic microscopy and dermoscopy. A therapeutic trial with topical minoxidil was conducted.

Displasia ectodérmica hipohidróticaa en dos hermanas / Hypohidrotic ectodermal dysplasia in two sisters

La displasia ectodérmica hipohidrótica es un síndrome congénito, caracterizado por la tríada hipohidrosis, hipotricosis e hipodoncia no progresivas. La forma más común es lade herencia recesiva ligada al cromosoma X, aunque también existe una autosómica recesiva y otra dominante. Su tratamiento incluye un manejo interdisciplinario, con medidas de soporte para las manifestaciones clínicas del trastorno y el asesoramiento genético familiar.

Hypohidrotic ectodermal dysplasia is a congenital syndrome characterized by the triad of hypohidrosis, hypotrichosis and non-progressivehypodontia. The most common form is the one inherited in a recessive X-linked way, although there is also an autosomal recessive and a dominant ones. Treatment includes the interdisciplinary management, supportive for the clinical manifestations of the disorder and family genetic counseling.

Ectodermal dysplasia: familial report of six cases.

Ectodermal dysplasia is a hereditary disease characterized by a congenital dysplasia of one or more ectodermal structures and their accessory appendages. There are two main types, Hypohidrotic/Christ-Seimens- Tourian Syndrome and Hidrotic/Clouston syndrome. Common manifestations include defective hair follicles and eyebrows, frontal bossing with prominent supraorbital ridges, nasal bridge depression and protuberant lips. Intraorally common findings are anodontia or hypodontia and conical shaped teeth. The patient may suffer from dry skin, hyperthermia and unexplained high fever because of the deficiency of sweat glands. The present article reports unique case series of ectodermal dysplasia cases in two families, where three generations in the both the families were affected.

Graham-Little Piccardi Lassueur Syndrome: case report / Síndrome de Graham-Little Piccardi Lassueur: relato de caso

A 33-year-old woman presented with a 3-year history of progressive alopecia of the scalp. Past treatment with hydroxicloroquine did not show improvement. Physical examination revealed multiple areas of alopecia with atrophic aspect of the scalp, and axillary and pubic hypotrichosis. Dermoscopy showed hyperkeratosis and accentuation of follicular ostia. Anatomopathological examination revealed decrease in the number of hair follicles, upper perifollicular infiltrate and areas with fibrosis. The Piccardi-Lassueur-Graham-Little syndrome is a rare disorder, characterized by the triad of multifocal scarring alopecia of the scalp, keratotic follicular eruption and hypotrichosis of axillary and pubic regions. Management is a challenge and many medications tried have controversial results. We report a case of this rare syndrome which improved with corticoids.

Mulher, 33 anos, apresenta quadro de alopecia progressiva do couro cabeludo há 3 anos. Tratamento com hidroxicloroquina há 12 meses, sem apresentar melhora. Ao exame físico exibe múltiplas áreas de alopecia cicatricial no couro cabeludo, além de hipotricose axilar e pubiana. A dermatoscopia evidencia hipercetose folicular e acentuação dos óstios foliculares. O exame anatomopatológico revela diminuição do número de folículos pilosos, infiltrado perifolicular e fibrose. A síndrome de Graham-Little Piccardi Lassueur é uma dermatose rara, caracterizada pela tríade de alopecia cicatricial multifocal do couro cabeludo, ceratose folicular disseminada e hipotricose das regiões axilares e pubianas. A terapêutica desta dermatose é um desafio, muitas medicações relatadas tem resultados controversos. Relatamos o caso desta síndrome rara que apresentou melhora com corticoterapia.

Two Cases of Hallermann-Streiff Syndrome Diagnosed in Early Neonatal Period

Hallermann-Streiff syndrome is a very rare congenital disorder, which is primarily characterized by the head and face abnormalities. Approximately 180 cases have been reported worldwide, including 8 cases in Korea since it was first described by Hallermann in 1893. Patients exhibit a bird-like face, hypotrichosis, atrophy of skin, dental abnormalities, proportionate nanism, and various ophthalmic disorders, including congenital cataracts and bilateral micropthalmia. As a result of many life-threatening complications, such as respiratory and cardiac difficulties, many patients die during infancy. We report here two cases of HSS diagnosed immediately after birth with literature reviews. They showed two additional characteristics, including chubby cheeks and antenatal ultrasonographic findings, which have not been mentioned in previous reports.

Prosthodontic management of anhidrotic ectodermal dysplasia.

Ectodermal dysplasia is characterized by the absence or defects of two or more ectodermally derived structures. Anodontia or hypodontia is the most striking dental manifestation. In severe hypodontia, there is lack of alveolar development with consequent protrusion and eversion of the lips. Patients with anhidrotic forms suffer from heat intolerance due to lack of sweat glands and mild infections may lead to death in infancy from hyperthermia. A case of a 4-year-old child with anhidrotic ectodermal dysplasia with partial anodontia is presented. Dental, oral, and physical features were taken into consideration in diagnosis and treatment planning for this patient. Clinical management consisted of removable partial prosthesis in maxillary arch and complete denture prosthesis in mandibular arch. The main aim of the treatment was to improve psychological development and to promote better functioning of the stomatognathic system.

Non-familial Generalized Hypotrichosis Simplex / 대한피부과학회지

Hypotrichosis simplex is a descriptive term of hair loss without other ectodermal or systemic abnormalities. Hypotrichosis simplex with non-familial and generalized types has been seldom reported. A 30-year-old man visited our clinic complaining of scalp hair loss since birth. There was no hair on the arms, axillae and legs. He had relatively scanty eyebrows and pubic hairs. None of his family members had known health problems or any hereditary disease. Hair shaft examination based on electron microscopy did not reveal any structural abnormalities. Microscopic examination of a scalp biopsy specimen showed a reduced number of hair follicles with vellus hairs replacing terminal hairs. Herein we report a rare and interesting case of non-familial generalized hypotrichosis simplex.

Ectodermal dysplasia : report of a rare case.

Ectodermal Dysplasia (ED) is a hereditary congenital disorder of ectodermal origin. It is characterized by lack of sweat glands, (hypohydrosis), Alopecia (Hypotrichosis), defective palms and soles (Palmoplantar hyper keratosis) and oral presentation of partial absence of teeth, (hypodontia) or complete absence of teeth (anodontia). Hypodontia of primary and permanent dentition is one of the most frequently occurring oral symptoms in ectodermal Dysplasia. We report an unusual case of ectodermal dysplasia effecting soles and palms along with oral manifestations.

Algoritmo para as alopécias cicatriciais e suas opções de tratamento / Algorithm for approaching scar alopecia and treatment options

A cirurgia plástica dispõe de um variado arsenal de técnicas para o tratamento das alopéciascicatriciais. A correção cirúrgica dos defeitos do couro cabeludo deve começar por uma sistematizaçãoda classificação das lesões. A proposta de um algoritmo tem por objetivo organizarde maneira racional as opções para cada caso, sem, no entanto, substituir o julgamento e acriatividade do cirurgião. Este trabalho apresenta um raciocínio clínico que poderá facilitara escolha da melhor opção cirúrgica para corrigir cicatrizes do couro cabeludo.

Plastic surgery has a varied arsenal of techniques for the treatment of scar alopecia. Thesurgical correction of scalp defects should begin with a systematic classification of thetype of injury. An algorithm has been developed that rationalizes and organizes the surgicaloptions in each case, without attempting to replace the surgeon’s judgment and creativity.This paper presents a clinical analysis that could assist the selection of the best surgicalalternative for different cases of scar alopecia.