Skin findings in BPS include leukonychia, knuckle pads, and palmoplantar keratoderma (PPK). Leukonychia is often complete and involves all nails, although rarely partial leukonychia may occur. Leukonychia may improve with age. Patients generally develop hyperkeratotic lesions (knuckle pads and keratoderma) during childhood and adolescence. Knuckle pads in BPS are well-defined, hyperkeratotic papules over the dorsal small joints of the hands and feet. PPK, when present, is generally diffuse and striate with accentuation in skin creases.
Hearing loss in BPS is often present at birth (prelingual). Hearing loss is most often sensorineural due to cochlear defects. There have been reports of mixed or conductive hearing loss as well.
BPS is due to mutations in the gap junction β2 gene (GJB2), which encodes connexin 26. Other diseases involving GJB2 mutations include keratitis-ichthyosis-deafness (KID) syndrome and Vohwinkel syndrome, as well as hystrix-like ichthyosis deafness syndromes, palmoplantar keratoderma with deafness, and deafness with Clouston-like phenotype.
Clinical overlap between syndromes, including BPS, KID syndrome, and Vohwinkel syndrome, may occur. Moreover, within a family with BPS, there may be variable phenotypic expressivity among individuals.
Q82.8 – Other specified congenital malformations of skin
1271009 – Knuckle pads, deafness AND leukonychia syndrome
Differential Diagnosis & Pitfalls
- KID syndrome – Also caused by GJB2 mutations and involves sensorineural deafness; presents with corneal changes (keratitis) and differing skin changes of red, rough skin plaques (erythrokeratoderma) and ichthyosis.
- Vohwinkel syndrome – Also caused by GJB2 mutations and involves sensorineural deafness; presents with mutilating PPK with circular constriction bands of the digits (pseudoainhum) and starfish-like or stellate keratoses over the dorsal knuckles.
- Pseudo-knuckle pads – Associated with occupational trauma and friction and improve after the inciting cause is removed.
- Rheumatoid nodules – Can occur over joints but often with symptoms of rheumatoid arthritis; occur subcutaneously as opposed to epidermal thickenings; differentiable on pathology.
- Erythema elevatum diutinum – Can occur over joints, as well as on dorsal hands and extremities; can be tender or asymptomatic; often yellow to pink-brown in color; differentiable on pathology.
- Starfish-like keratoses – See Vohwinkel syndrome.
- Keratodermas with transgrediens (eg, mal de Meleda).