#149200
ICD+
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| KNUCKLE PADS, LEUKONYCHIA, AND SENSORINEURAL DEAFNESS | |||||||||||||||
| Alternative titles; symbols | |||||||||||||||
| BART-PUMPHREY SYNDROME | |||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||
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| Clinical Synopsis | |||||||||||||||
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| A number sign (#) is used with this entry because Bart-Pumphrey syndrome can be caused by mutation in the GJB2 gene (121011). | |||||||||||||||
| Clinical Features | |||||||||||||||
| Bart and Pumphrey (1967) described a kindred in which many members had knuckle pads, leukonychia, and deafness due to a lesion of the cochlea. Keratosis palmaris et plantaris was present in some. Male-to-male transmission was thought to have occurred in 2 instances. The condition described by Schwann (1963) was probably the same. The presence of leukonychia and the absence of digital constrictions appear to distinguish this disorder from the one listed as 'deafness, congenital, with keratopachydermia and constrictions of fingers and toes' (i.e., Vohwinkel syndrome, 124500). A family reported by Crosby and Vidurrizaga (1976) established that keratosis palmoplantaris, probably developing only in older affected persons, is part of the syndrome. Knuckle pads on the toes were pictured. Ramer et al. (1994) described this disorder in 5 members of a family and reviewed other disorders that are associated with knuckle pads. Richard et al. (2004) described a 3-generation Polish family with Bart-Pumphrey syndrome. All affected family members, including the maternal grandmother and uncle, presented with congenital deafness and developed diffuse, sharply demarcated thickening of palms and soles during early childhood. In the proband, an audiogram at 24 years of age demonstrated profound bilateral sensorineural hearing loss with normal middle ear function. Palmoplantar keratoderma had locally an almost punctate surface reminiscent of Vohwinkel syndrome, and was most profound over the heels and in interphalangeal folds, resulting there in the formation of hard, hyperkeratotic bands. Before puberty, 2 affected individuals had developed fixed, hyperkeratotic plaques with a verrucous surface over the metacarpo- and interphalangeal joints that regressed over time in 1. Two affected individuals had leukonychia. Light microscopic evaluation of skin biopsies revealed massive orthokeratotic hyperkeratosis without evidence for retained nuclei, hypergranulosis, acanthosis, and papillomatosis. Epidermal gap junctions appeared normal on electron microscopic evaluation. | |||||||||||||||
| Molecular Genetics | |||||||||||||||
| In a multigeneration Polish family with Bart-Pumphrey syndrome, Richard et al. (2004) reported a novel nonconservative missense GJB2 mutation (121011.0030) segregating with the disorder. This mutation, not detected in 110 control individuals of northern European ancestry, lies within a cluster of pathogenic GJB2 mutations affecting the evolutionarily conserved first extracellular loop of Cx26 important for docking of connexin hemichannels and voltage gating. Immunostaining of Cx26 in lesional palmar and knuckle skin was weak or absent, although its adnexal expression appeared normal and the punctate membrane staining of Cx26 and other epidermal connexins was not altered. Nevertheless, the widespread immunostaining of Cx30 (GJB6; 604418) throughout the spinous cell layers suggested a compensatory overexpression. | |||||||||||||||
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