Hypotrichosis-Osteolysis-Periodontitis-Palmoplantar Keratoderma Syndrome

Clinical Features

Van Steensel et al. (2002) reported a mother and daughter with a syndrome of hypotrichosis, striate palmoplantar keratoderma, onychogryphosis, periodontitis, acroosteolysis, and psoriasis-like skin lesions. The syndrome resembled Papillon-Lefevre syndrome (245000), characterized by palmoplantar keratoderma, periodontitis, and psoriasis-like skin lesions, and particularly Haim-Munk syndrome (245010), an allelic variant of Papillon-Lefevre with acroosteolysis. Both are caused by mutations in the cathepsin C gene (602365). The patients reported by Van Steensel et al. (2002) differed in the nature of the palmar keratoderma and hypotrichosis. Additionally, they lacked the pes planus seen in Haim-Munk syndrome. The proband had dystrophic nails and absent eyebrows and lashes since birth, with thickened palmoplantar skin since the age of 2 years. At age 7 years, her scalp hair, which had always been thinly implanted, started to fall out; hair loss was not accompanied by other symptoms such as pustules, itching, or scaling. Cutting her strongly curved nails was nearly impossible, as it was very painful and accompanied by bleeding. Around the same time, her teeth began to be affected by caries, and periodontitis became apparent. At about 15 years of age, erythematous scaly lesions appeared on the lower arms and legs. Electron microscopic examination of the hair showed pili torti et annulati. At age 27, both hands showed significant onychogryphosis with several fingers apparently lacking distal phalanges. All digits were thin and tapered towards the tips. At age 52, peculiar, reticulate pitted hyperkeratosis of the palms, spiky hyperkeratosis of the soles, hypotrichosis universalis, and lingua plicata were noted. The hypotrichosis of the scalp seemed secondary to scarring alopecia, as hair follicle openings were missing over most of the scalp. The hyperkeratosis of the palms was highly unusual, following a reticular pattern and showing many small 'pinprick' pits. She developed ventricular tachycardia in the fifth decade of life. The proband had an affected daughter who developed nail abnormalities at age 3 months. Hyperkeratoses of the feet appeared at age 2 years. At the age of 13 years, she developed joint pains. Periarticular bone density was decreased, suggesting that the daughter, too, might be suffering from osteolysis. Physical examination showed onychogryphosis, hypotrichosis, periodontitis, and lingua plicata. She also had palmoplantar keratoderma, but in her case the palmar keratoderma was nummular rather than linear. The plantar keratoderma was similar to that seen in her mother. She had erythematous, scaling lesions on the lower arms and legs. The hypotrichosis and periodontitis were less severe than in the mother. Histology of a skin biopsy from a hyperkeratotic area from the mother showed pronounced orthohyperkeratosis but no other abnormalities. The biopsy from a psoriasis-like region on the leg showed hyperplasia and hyperparakeratosis. The granular layer was absent. The dermal papillae were elongated but did not show the tongue shape typical for psoriasis. In the upper dermis, there was a perivascular lymphocytic infiltrate. A biopsy slide of the daughter showed identical abnormalities. Examination of a scalp biopsy showed a reduced number of hair follicles and only slight scarring. The mode of inheritance could not be determined unambiguously as there were only 2 affected individuals, but an autosomal dominant mode was considered most likely.

Molecular Genetics

Van Steensel et al. (2002) sequenced the CTSC gene in the proband and found no mutations in either coding or noncoding parts of the gene. They proposed that their patients suffered from a theretofore undescribed syndrome possibly caused by mutations in a gene that has a functional or structural relation with CTSC.