Familial comedones. Evidence for autosomal dominant inheritance.

Thirteen members of a family had multiple comedones. Three other relatives were also ascertained to be affected. This peculiar dermatosis affected both sexes and was present in one individual as young as 10 years of age. The lesions were more numerous in male family members, increasing in number with age. The pedigree showed a definite pattern of autosomal dominant inheritance.     

Hereditary hypotrichosis simplex of the scalp

Hereditary hypotrichosis simplex of the scalp is a genotrichosis characterized by sparse or absent scalp hair without structural defects, in the absence of other ectodermal or systemic abnormalities. We describe two Spanish families with hypotrichosis of the scalp. We believe these families have Toribio and Quiñones type hereditary hypotrichosis simplex of the scalp.     

Hereditary hypotrichosis simplex of the scalp

A peculiar variety of hereditary hypotrichosis is described. The abnormality has affected a large family over the course of eight generations. This genealogy is the fullest so far known of hereditary hypotrichosis. The condition is a hypotrichosis limited to the scalp, which first manifests itself in the early school-years. Afterwards the loss of scalp hair gradually progresses to almost total alopecia. This terminal stage is reached between the ages of 20 and 25 years, and the condition affects males and females in a similar way. From the genetic point of view, the abnormality is transmitted with an autosomal dominant mode of inheritance with full penetrance.     

常染色体显性遗传性少毛症分子遗传学研究进展

遗传性少毛症是一种表现为毛发永久性部分或完全缺失的单基因遗传性疾病,按遗传异质性分为常染色体显性遗传、常染色体隐性遗传、X连锁显性遗传、X连锁隐性遗传。本文重点介绍常染色体显性遗传性少毛症的各种亚型:遗传性单纯性头皮性少毛症(HSS)、遗传性单纯性少毛症(HHS)、Marie Unna型少毛症(MUHH)、常染色体显性羊毛状发(ADWH)、生长期毛发松动综合征(LAHS)等分子遗传学研究进展。     

Familial aplasia cutis congenita of the scalp without other defects in 6 members of three successive generations

Six cases of isolated aplasia cutis congenita of the scalp among family members over three successive generations are described suggesting an autosomal dominant inheritance. Five family members were examined in our clinic while one member is abroad. A review of the literature concerning isolated congenital aplasia cutis of the scalp in three or more generations is done.     

A novel mutation in LPAR6 causes autosomal recessive hypotrichosis of the scalp

Background. Autosomal recessive hypotrichosis simplex (ARHS) presents with progressive hair loss mainly affecting the scalp area. In a small number of families, the condition has been associated with mutations in three distinct genes: DSG4, LIPH and LPAR6. Aim. To identify the molecular basis of ARHS in a consanguineous family of Turkish extraction. Methods. We used a combination of microsatellite marker screening and direct sequencing. Results. We identified a novel missense mutation (c.C587T) in the human LPAR6 gene, resulting in the amino acid substitution p.P196L. The mutation affects a highly conserved amino acid residue, and is predicted to disrupt signalling through the P2Y5 receptor. Conclusions. This study provides further evidence supporting a role for the lysophosphatidyl signalling pathway in hair growth and differentiation. In addition, this paper reports, for the first time to our knowledge, the use of homozygosity mapping as a premutation screening tool in the diagnosis of a group of inherited hair disorders.     

Familial nonmembranous aplasia cutis of the scalp

Aplasia cutis of the scalp is often a sporadic condition, but familial occurrences with an autosomal dominant inheritance have been documented. Aplasia cutis of the scalp may be seen in two main clinical variants: oval-shaped membranous aplasia cutis and irregular, larger defects. We report six families in whom more than one member has aplasia cutis of the scalp, all of them with large irregular defects located over the vertex or anterior to the vertex along the sagittal suture. We review previous reports of this entity with clinical pictures and note that in most instances, the defects are of the nonmembranous variant.     

Topical fluocinolone acetonide acetate ointment in autosomal dominant congenital hypotrichosis

Hypotrichosis present at birth occurring as an isolated defect in three members of an Afghan family and transmitted as an autosomal dominant trait, responded to topical applications of fluocinolone acetonide acetate ointment. The patients were a 9-year-old boy, his 7-year-old sister and their 30-year-old mother who since birth, had sparse, light-coloured and thin hairs on their scalp which would not grow longer than 1 cm in length. Microscopic examination revealed the hairs to be thin and fragile, but of a uniform thickness. Some of the hairs showed secondary trichorrhexis. Following topical applications of 0.1% fluocinolone ointment, the hairs became coarser and increased in length from an ayerage of 0.7 cm before treatment to 6.2 and 7.1 cm in the two children after 10 months. The mother who started the treatment later also showed improvement.     

Incontinentia pigmenti in four generations

Clinical and genetical aspects of a family with incontinentia pigmenti (IP) in 5 female members belonging to four successive generations are reported. In 4 individuals IP was associated with dental anomalies and partial hypodontia. Three of them also had convulsive disorders.     

Mutations in the CDSN gene cause peeling skin disease and hypotrichosis simplex of the scalp

Peeling skin disease is a rare genodermatosis characterized by superficial exfoliation or peeling of the skin. Peeling skin disease is caused by biallelic mutations in CDSN as an autosomal recessive trait. Monoallelic mutations in CDSN have also been described in an autosomal dominant inherited genodermatosis: hypotrichosis simplex of the scalp. This disease is characterized by progressive hair loss of the scalp with onset after early childhood. Clinical data were obtained from a patient with lifelong generalized skin peeling and both his parents. The patient's parents did not suffer from skin peeling, but the mother had a history of thin scalp hair since early childhood. Mutation analysis in the patient showed compound heterozygous mutations in exon 2 of CDSN, a nonsense mutation c.598C>T (p.[Gln200*]), previously associated with hypotrichosis simplex of the scalp, and a frame-shift mutation c.164_167dup (p.[Thr57Profs*6]), previously described in peeling skin disease. The p.(Gln200*) mutation was also found in the mother of the proband. Our study strengthens the previously established link between mutations in CDSN to peeling skin disease and hypotrichosis simplex of the scalp.     

Familial presentation of multiple scalp tumors

A 74-year-old woman was referred for evaluation and treatment of a tumor measuring 3 x 2 cm in the left preauricular region that has been progressively growing in the past years. Physical examination revealed an hemispheric and firm tumor with reddish coloration and telangiectases. The patient has been using a wig during the past 15 years to cover the scalp lesions. The patient underwent complete surgical excision of the scalp and the defect was reconstructed with partial-thickness grafts. Given the long-standing evolution and extension of the tumors involving the scalp and face we suspected a familial cylindromatosis syndrome therefore, we revised her six children observing scalp tumors in two daughters. The tumors were excised and the histological findings confirmed the diagnosis of cylindromas.     

Steatocystoma multiplex in four successive generations

A 16-year-old girl presented with multiple, yellowish, elastic, non-tender cysts on the face, trunk, arms and axillae for the last 3-4 years. On pricking, yellowish fluid could be expressed from the lesions. Clinically and histopathologically, the lesions were suggestive of steatocystoma multiplex. There was a family history of similar lesions in five members over four generations.     

A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp

BACKGROUND: Hypotrichosis simplex of the scalp (HSS; MIM 146520) is a rare autosomal dominant form of non-syndromic alopecia that affects men and women equally. Up to now, only a small number of families with HSS have been reported. The affected individuals experience a diffuse progressing hair loss from childhood to adulthood that is confined to the scalp. Recently, HSS has been mapped to the short arm of chromosome 6 (6p21.3), allowing mutations in the corneodesmosin gene (CDSN) to be identified as the cause of the disorder. To date, two stop mutations have been found in three unrelated families with HSS of different ethnic origin. OBJECTIVES: To describe the first HSS-family with Latin American (Mexican) background comprising 6 generations and to identify a mutation in the CDSN gene. PATIENTS/METHODS: The patients were examined by a clinician and blood samples were taken. After DNA extraction, sequencing analysis of the CDSN gene and restriction enzyme analysis with PsuI were performed. RESULTS: By direct sequencing of the two exons of the CDSN gene, a nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239X). The mutation co-segregates perfectly in the family with the disease and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI. CONCLUSIONS: A nonsense mutation was identified in the first family with HSS of Latin American ethnical background. Our data provide molecular genetic evidence for a 3rd stop mutation in exon 2 of the CDSN gene being responsible for HSS. All to date known nonsense mutations responsible 3 for HSS are clustered in a region of 40 amino acids which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins.