Alternative titles; symbols
SNOMEDCT: 1271009; ORPHA: 2698; DO: 0050658;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 13q12.11 | Bart-Pumphrey syndrome | 149200 | Autosomal dominant | 3 | GJB2 | 121011 |
A number sign (#) is used with this entry because of evidence that Bart-Pumphrey syndrome (BAPS) is caused by heterozygous mutation in the GJB2 gene (121011) on chromosome 13q12.
Bart-Pumphrey syndrome (BAPS) is an autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, which shows considerable phenotypic variability (summary by Richard et al., 2004).
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 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.
The transmission pattern of BAPS in the family studied by Richard et al. (2004) was consistent with autosomal dominant inheritance.
In a multigeneration Polish family with Bart-Pumphrey syndrome, Richard et al. (2004) identified 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.
In a 26-year-old male with Bart-Pumphrey syndrome, Alexandrino et al. (2005) identified heterozygosity for a missense mutation in the GJB2 gene (121011.0035).
Alexandrino, F., Sartorato, E. L., Marques-de-Faria, A. P., Steiner, C. E. G59S mutation in the GJB2 (connexin 26) gene in a patient with Bart-Pumphrey syndrome. (Letter) Am. J. Med. Genet. 136A: 282-284, 2005. [PubMed: 15952212] [Full Text: https://doi.org/10.1002/ajmg.a.30822]
Bart, R. S., Pumphrey, R. E. Knuckle pads, leukonychia and deafness--a dominantly inherited syndrome. New Eng. J. Med. 276: 202-207, 1967. [PubMed: 6015974] [Full Text: https://doi.org/10.1056/NEJM196701262760403]
Crosby, E. F., Vidurrizaga, R. H. Knuckle pads, leukonychia, deafness and keratosis palmoplantaris: report of a family. Johns Hopkins Med. J. 139: 90-92, 1976. [PubMed: 138007]
Ramer, J. C., Vasily, D. B., Ladda, R. L. Familial leuconychia, knuckle pads, hearing loss, and palmoplantar hyperkeratosis: an additional family with Bart-Pumphrey syndrome. J. Med. Genet. 31: 68-71, 1994. [PubMed: 8151643] [Full Text: https://doi.org/10.1136/jmg.31.1.68]
Richard, G., Brown, N., Ishida-Yamamoto, A., Krol, A. Expanding the phenotypic spectrum of Cx26 disorders: Bart-Pumphrey syndrome is caused by a novel missense mutation in GJB2. J. Invest. Derm. 123: 856-863, 2004. [PubMed: 15482471] [Full Text: https://doi.org/10.1111/j.0022-202X.2004.23470.x]
Schwann, J. Keratosis palmaris et plantaris cum surditate congenita et leuconychia totali unguium. Dermatologica 126: 335-353, 1963. [PubMed: 14046203]