Keratoderma with woolly hair type II
It is caused by a mutation in the DSP gene on chromosome 6, which encodes for desmoplakin, a desmosomal protein found in cardiac tissue and the skin. The mutated protein has a truncated C-terminal domain that is responsible for intermediate filament binding. The DSP mutation is inherited in an autosomal recessive manner, but autosomal dominant forms have also been identified.
Carvajal syndrome is exceedingly rare, with only a handful of documented cases in Ecuador, India, Saudi Arabia, and Turkey.
Woolly hair presents as tightly coiled, unusually frizzy, difficult-to-comb hair diffusely on the scalp that is apparent at birth. Palmoplantar hyperkeratosis begins in the first year of life. The keratoderma is usually striate or focal and keratotic plaques may be seen over elbows and knees, as well as in the flexures. A left-sided dilated ventricular cardiomyopathy typically results in cardiac failure, and affected individuals begin to develop symptoms and signs in early childhood. Sudden cardiac death may occur from ventricular arrhythmias, but progressive cardiac failure is the most common cardiac presentation. Most patients will die before reaching adulthood. Affected individuals with the autosomal dominant form may also manifest oligodontia.
Q82.8 – Other specified congenital malformations of skin
Q84.1 – Congenital morphological disturbances of hair, not elsewhere classified
719835006 – Keratoderma with woolly hair type II
Differential Diagnosis & Pitfalls
- Skin fragility-woolly hair syndrome (SFWHS) is an autosomal recessive disease characterized by focal and diffuse PPK, woolly hair, recurrent bullae, and nail dystrophy, without the presence of cardiomyopathy
- Trichohepatoenteric syndrome – diffuse woolly hair on the scalp, trichorrhexis nodosa, failure to thrive, infantile diarrhea, and liver disease
- Hereditary woolly hair – no additional clinical features present
- Uncombable hair syndrome
- Pili torti
- Trichorrhexis nodosa
- Keratoderma with woolly hair type 1 (Naxos disease) – diffuse nontransgrediens keratoderma, woolly hair, ARVD/C
- Keratoderma with woolly hair type 3 – diffuse nontransgrediens keratoderma, milder extracardiac symptoms than type 1
- Keratoderma with woolly hair type 4 – nontransgrediens, woolly or sparse hair, irregularly curved fingernails and toenails, no cardiac involvement
- McGrath Syndrome – woolly hair and PPK are seen; however, cheilitis, perioral fissures, redness, and normal cardiac function are discriminating factors
- Erythrokeratodermia cardiomyopathy syndrome – woolly hair, cardiomyopathy; however, ichthyosis is the differentiating skin abnormality
- SAM syndrome – PPK, dermatitis; biopsy shows subcorneal separation with mild acantholysis
- Isolated focal PPKs (striate PPKs) are due to autosomal dominant mutations in genes encoding desmosomal proteins. Lesions favor pressure points on feet and may present as linear plaques on hands.
- Howel-Evans syndrome is associated with mutations in the TOC gene, focal weight-bearing area plantar hyperkeratosis, milder palm involvement, and development of esophageal carcinoma.
- Richner-Hanhart syndrome is associated with mutations in the gene that encodes tyrosine aminotransferase. Accumulation of tyrosine leads to focal (or diffuse) hyperkeratotic plaques on the hands, feet, elbows, and knees, corneal inflammation / ulceration, and intellectual disability in some cases. Diets low in phenylalanine and tyrosine may prevent complications.
- Focal PPK may also be seen in pachyonychia congenita type I and type II.