Palmoplantar Keratoderma, Mutilating, With Periorificial Keratotic Plaques, X-Linked

A number sign (#) is used with this entry because of evidence that X-linked mutilating palmoplantar keratoderma with periorificial keratotic plaques (Olmsted syndrome) is caused by mutation in the MBTPS2 gene (300294) on chromosome Xp22. One such family has been reported.

Description

Olmsted syndrome is a rare keratinization disorder characterized by the combination of periorificial keratotic plaques and bilateral palmoplantar transgredient keratoderma. Other clinical manifestations include diffuse alopecia, leukokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic linear streaks, follicular keratosis, and constriction of the digits (summary by Yaghoobi et al., 2007).

An autosomal dominant form of Olmsted syndrome (614594) is caused by mutation in the TRPV3 gene (607066) on chromosome 17p13.

Clinical Features

Yaghoobi et al. (2007) described a 20-year-old Iranian man with alopecia universalis and hyperkeratotic lesions, particularly of the palmoplantar areas and around orifices. At 6 months of age, he developed small hyperkeratotic lesions on his neck, elbows, buttocks, palms, and soles, which gradually became massive hyperkeratoses with painful deep fissures, especially on the palms and soles. Examination showed sharply marginated thick, verrucous, and erythematous hyperkeratotic plaques around the mouth, nostrils, posterior neck, outer forearms, groin, genitalia, intergluteal area, and extensor surfaces of knees and legs. There were diffuse yellowish-brown hyperkeratoses with deep fissures extending to the wrists and external borders of his hands and feet. The palmoplantar keratoderma caused severe flexion contractures, so that the proband was unable to walk or grasp. All lesions were pruritic and painful. His nails were hyperkeratotic, fork-like, yellow, and severely dystrophic with subungual hyperkeratosis. There were no intraoral lesions except for bilateral absence of premolar teeth. Ophthalmologic examination revealed bilateral chronic blepharitis with loss of lashes and meibomian gland dysfunction; slit-lamp examination showed subepithelial and anterior stromal opacities with corneal vascularization extending to the central cornea. Histologic examination of a forearm lesion showed hyperkeratosis, parakeratosis, mild acanthosis, and papillomatosis, with mild perivascular lymphocytic infiltration of the dermis. Biopsy of an exophytic mass on his right sole showed massive hyperkeratosis, parakeratosis, acanthosis, and prominent papillomatosis, with moderate acute and chronic inflammation of the dermis. The proband's parents and sibs were unaffected but he had a 7-year-old nephew with alopecia universalis who, at 5 months of age, developed bilateral palmoplantar thickening and scaly erythema around his mouth and on his elbows and knees. The lesions became hyperkeratotic by 2 years of age. Examination at age 7 showed alopecia of the scalp and eyebrows, with well-defined, mildly hyperkeratotic plaques around the mouth and nares. Symmetric, thick, sharply marginated yellowish-red areas of hyperkeratosis affected the extensor surfaces of his elbows, knees, hands, and feet. His fingertips showed mild scaly erythema without dystrophic nails. Keratoderma was also present, especially on the weight-bearing areas of his soles. Physical and mental development was otherwise normal in both patients, and hearing was intact in both.

Molecular Genetics

In a consanguineous Iranian family originally described by Yaghoobi et al. (2007), in which an uncle and nephew exhibited features of Olmsted syndrome and were negative for mutation in the TRPV3 (607066), GJB2 (121011), GJB3 (603324), GJB4 (605425), GJB6 (604418), DSP (125647), and JUP (173325) genes, Haghighi et al. (2013) performed whole-exome sequencing and identified a missense mutation in the MBTPS2 gene (F464S; 300294.0008) on chromosome Xp22. Female family members did not exhibit any clinical features of Olmsted syndrome, and the affected males did not have features specific to BRESHECK syndrome (see 308205) such as hearing loss, skeletal abnormalities, or dysmorphic features.

Wang et al. (2014) described a 22-year-old Han Chinese man who exhibited features of both IFAP (308205) and Olmsted syndromes, including ichthyosis, total alopecia, photophobia, short stature, inguinal hernia, palmoplantar and periorificial keratoderma, and pachyonychia, in whom they identified an intronic mutation in the MBTPS2 gene (300294.0007) that had previously been identified in IFAP patients by Oeffner et al. (2011). Wang et al. (2014) designated the phenotype in their patient as 'IFAP with Olmsted syndrome-like features' and questioned whether X-linked Olmsted syndrome represented an independent condition or merely a severe form of IFAP.