Inherited syndrome with knuckle pads, leukonychia, and sensorineural deafness.
Knuckle Pads, Leuconychia, Sensorineural Deafness Syndrome; Knuckle Pads, Leukonychia, Sensorineural Deafness, Palmoplantar Hyperkeratosis Syndrome; Knuckle Pads, Leukonychia, Sensorineural Deafness, Palmoplantar Keratoderma Syndrome.
Named after the two American physicians Robert S. Bart (a dermatologist) and Robert E. Pumphrey (an otolaryngologist), who described the disease in 1967. However, Jadwiga Schwann, a dermatologist from Poland most likely described the same disorder already in 1963, although in her report, only males were affected.
The incidence and prevalence remain unknown.
Inheritance is autosomal dominant. The mutations affect the GJB2 (gap junction beta 2 or connexin 26) gene encoding the gap junction protein connexin 26 (Cx26), which has been mapped to chromosome 13q12. It has been estimated that up to 50% of genetic nonsyndromic hearing loss is caused by mutations in GJB2 gene.
A gap junction consists of two hemichannels, one on either side of opposing cell membranes of neighboring cells. These hemichannels (or connexons), each composed of six connexin subunits and anchored perpendicularly in the cell membrane, connect precisely to one another to form a central pore connecting the cytoplasms of the two cells. These gap junctions act as a tunnel for ions (potassium) and smaller molecules. The hemichannels can consist of either a single type of connexin subunits or a combination of different connexins. Cx26 is expressed in most tissues of the body, including the skin and the cochlea. The gap junctions in the cochlear cells help maintaining the potassium gradients required for the conversion of sound waves into electrical nerve impulses. In the cochlea, Cx26 is primarily found in supporting cells, fibrocytes in the spiral limbus, and ligament and in the stria vascularis, but is absent from the inner or outer hair cells or the marginal cells of the stria vascularis. Gap junctions have also been shown to allow passage of nonsignaling permeants, such as nutrients (eg, amino acids and glucose). The organ of Corti is avascular and gap junctions in surrounding cells may play a crucial role in the cochlear energy supply. In the skin, Cx26 is involved in growth regulation, migration, and differentiation of keratinocytes. However, Cx26 expression is limited to the palmoplantar epidermis, sweat glands, and hair follicles.
The phenotypic variability is considerable. Congenital, mild to severe sensorineural hearing loss is the most constant feature of this disorder and is caused by a cochlear defect (see “Pathophysiology”). The hearing loss seems to be more severe in female patients. Some patients additionally have features of conductive hearing loss. Skin findings include hyperkeratotic, verruciform plaques over the metacarpo- and interphalangeal joints (so-called knuckle pads). ...