Focal dermal hypoplasia in a male.

Focal dermal hypoplasia (FDH) is a rare mesoectodermal dysplasia syndrome characterized by cutaneous, skeletal, dental, ocular and soft-tissue defects. An X-linked dominant mode of inheritance with lethality in male subjects has been proposed. Only around 30 cases of FDH have been reported in male subjects. Live born affected males are mosaic for mutations in PORCN gene . We present the mosaic pattern of FDH in a young boy.

Epidemiology of epidermolysis bullosa in the antipodes: the Australasian Epidermolysis Bullosa Registry with a focus on Herlitz junctional epidermolysis bullosa.

OBJECTIVE: To present epidemiologic and clinical data from the Australasian Epidermolysis Bullosa (EB) Registry, the first orphan disease registry in Australia. DESIGN: Observational study (cross-sectional and longitudinal). SETTING: Australian private dermatology practice, inpatient ward, and outpatient clinic. PATIENTS: Systematic case finding of patients with EB simplex, junctional EB (JEB), and dystrophic EB and data collection were performed throughout Australia and New Zealand from January 1, 2006, through December 31, 2008. Patients were consecutively enrolled in the study after clinical assessment and laboratory diagnosis. Medical records were retrospectively examined, and physicians involved in EB care were contacted to obtain patient history. A Herlitz JEB case series was prepared from registry data. MAIN OUTCOME MEASURES: Demographics and prognosis of patients with Herlitz JEB. RESULTS: A total of 259 patients were enrolled in the study: 139 with EBS, 91 with dystrophic EB, 28 with JEB, and 1 with Kindler syndrome. Most enrollees were Australian citizens (n = 243), with an Australian prevalence rate of 10.3 cases per million. The age range in the registry was birth to 99 years, with a mean and median age of 24.1 and 18.0 years, respectively. Ages were similar in patients with EBS and dominant dystrophic EB but were markedly lower in patients with JEB. Patients with Herlitz JEB (n = 10) had the highest morbidity and mortality rates, with a mean age at death of 6.8 months. Sepsis, failure to thrive, and tracheolaryngeal complications were the leading causes of death. CONCLUSIONS: The Australasian EB registry is the first registry in Australia and New Zealand to provide original data on age, sex, ethnicity, and geographical and disease subtype distribution. The Australasian Herlitz JEB cohort witnessed a high infant mortality rate and poor prognosis overall.

Erythema induratum in a Kenyan child.

A 10-year-old Kenyan girl presented with a 9-month history of a persistent, painful eruption of multiple, tender, non-ulcerated, pigmented nodules involving the calves, shins and soles of the feet. She had recurring fevers particularly at night, lethargy, weight loss and a persistent non-productive cough. The Mantoux test was positive. Chest X-ray revealed mild peribronchial thickening in the hilar region but no evidence of hilar lymphadenopathy, consolidation and/or cavitation suggestive of tuberculosis. Sputum and gastric washings were negative for acid-fast bacilli. Histology on a skin biopsy showed a granulomatous panniculitis with no histological evidence of Mycobacterium tuberculosis, consistent with erythema induratum. In view of her constitutional symptoms, chronic non-productive cough and positive Mantoux test, she was diagnosed with pulmonary tuberculosis despite the non-specific chest X-ray and negative bacteriology. Anti-tuberculous therapy was initiated with pyrazinamide, isoniazid and rifampicin for 2 months followed by dual therapy with isoniazid and rifampicin for a further 4 months. Her constitutional and respiratory symptoms and skin eruption cleared within 6 months with treatment.

Multiple trichoepitheliomas in a mother and daughter.

A 38-year-old mother and her 8-year-old daughter presented with multiple facial papules. In both cases, the papules had started to develop at about the age of 4-5 years. Biopsy of one of the mother's papules revealed a trichoepithelioma. With time the lesions had become less obvious in the mother, so she and her daughter elected to have no treatment. Both mother and daughter were otherwise well. However, there have been rare reports of multiple trichoepitheliomas being associated with systemic conditions. Multiple trichoepitheliomas are inherited in an autosomal dominant manner and have been mapped to chromosome 9p21.

Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.

Erythrokeratodermia variabilis is an autosomal dominant genodermatosis characterized by persistent plaque-like or generalized hyperkeratosis and transient red patches of variable size, shape, and location. The disorder maps to a cluster of connexin genes on chromosome 1p34-p35.1 and, in a subset of families, results from mutations in the gene GJB3 encoding the gap junction protein connexin-31 (Cx31). A recent report suggested the involvement of another connexin gene (GJB4) in the etiology of erythrokeratodermia variabilis. In this study, we sequenced the coding region of GJB4 in 13 unrelated erythrokeratodermia variabilis families without detectable mutations in GJB3. Mutation analysis revealed six distinct missense mutations in five families and a sporadic case of erythrokeratodermia variabilis, all of which were not found in controls. Mutation G12D, identified in an extended Dutch family, lies in the predicted amino-terminus and may interfere with the flexibility of this domain, connexin selectivity, or gating polarity of gap junction channels. Other mutations (R22H, T85P, F137L, F189Y) were located in the transmembrane domains of Cx30.3, and are predicted to hinder regulation of voltage gating or alter the kinetics of channel closure. Affected individuals of two unrelated families harbored point mutations leading to amino acid substitution F137L, which was also reported in GJB3, yet the extent and severity of hyperkeratosis was milder compared to the corresponding mutation in GJB3. Two mutations (T85P, F137L) were associated with the occurrence of rapidly changing erythematous patches with prominent, circinate, or gyrate borders in affected children but not in adults, supporting the notion that this feature is specific to Cx30.3 defects. Nevertheless, we observed highly variable intrafamilial phenotypes, suggesting the strong influence of modifying genetic and epigenetic factors. In addition to pathogenic mutations, we identified several missense mutations and a 4 bp deletion within the GJB4 coding region, which might represent either inconsequential polymorphisms or recessive mutations. In conclusion, our results demonstrate genetic heterogeneity in erythrokeratodermia variabilis, and emphasize that intercellular communication mediated by both Cx31 and Cx30.3 is crucial for epidermal differentiation.