Ichthyosis, Hystrix-Like, With Deafness

A number sign (#) is used with this entry because HID syndrome is caused by heterozygous mutation in the GJB2 gene (121011), which is also mutant in KID syndrome (148210), on chromosome 13q12.

Clinical Features

Schnyder and Gloor (1977) and Gulzow and Anton-Lamprecht (1977) described a 17-year-old male with ichthyosis hystrix and bilateral hearing loss. Thereafter, sporadic cases of both sexes were reported (Baden and Bronstein, 1988; Badillet et al., 1982). Because of characteristic electron microscopic features, the disease was considered a distinct entity and was initially named 'ichthyosis hystrix gravior, type Rheydt' after the city of origin of the patient, located near Dusseldorf, Germany. Traupe (1989) suggested the designation hystrix-like ichthyosis with deafness, or HID syndrome. The disease became manifest shortly after birth with erythematous patches. At the age of 1 year, spiky and cobblestone-like hyperkeratotic masses involved the entire skin. The palms and soles were only mildly affected. Scarring alopecia also occurred. Histopathologic features resembled those of lamellar ichthyosis and were not diagnostic. Ultrastructural changes included excess formation of mucous-containing granules and reduction of tonofibrils.

Konig et al. (1997) reported the first instance of familial occurrence. The 3-month-old son of the patient reported in 1977 had neurosensory deafness and typical cutaneous involvement, including red hyperkeratotic papules on the face and disseminated induration of the entire skin with diffuse dark-yellow hyperkeratoses. An important differential diagnosis of HID syndrome is KID syndrome (keratitis, ichthyosis-like hyperkeratosis, and deafness), of which both autosomal dominant (148210) and autosomal recessive (242150) forms may exist. KID syndrome does not represent a true form of ichthyosis, however, but rather a particular type of erythrokeratodermia and can be differentiated from the HID syndrome by a number of features. Although both conditions show neurosensory deafness and proneness to bacterial and mycotic skin infections, the skin changes in KID syndrome may be present at birth in the form of hyperkeratotic erythroderma that resolves spontaneously. Later on, hyperkeratotic plaques recur but they never involve the trunk. The palms and the soles are severely affected, which represents a feature different from the HID phenotype. Moreover, the electron microscopic features observed in the 2 syndromes are different.

Van Geel et al. (2002) provided photographs of the first reported patient with HID syndrome (Schnyder and Gloor, 1977; Gulzow and Anton-Lamprecht, 1977). Extensive spiky hyperkeratosis covered most of the skin of the face and neck with a slightly erythrodermic aspect. Cobblestone-like hyperkeratosis was present on the scalp. Hypotrichosis of eyebrows, eyelids, and scalp was likewise present. Erythroderma and impressive cobblestone-like hyperkeratosis around the knees changed abruptly into a spiky hyperkeratosis in some areas.

Molecular Genetics

Because of similarities between HID syndrome and KID syndrome, which results from mutations in the connexin-26 gene (GJB2), van Geel et al. (2002) searched for mutations in the GJB2 gene in the first reported case of HID syndrome (Schnyder and Gloor, 1977; Gulzow and Anton-Lamprecht, 1977). They extracted DNA from paraffin-embedded tissue samples. Since the KID syndrome mutation, asp50 to asn (121011.0020), abolished an AspI restriction site, they analyzed this site by PCR and restriction digestion and demonstrated that the HID patient was heterozygous for lack of the restriction site. Subsequently, they confirmed the presence of the mutation by direct sequencing and found no additional variations in the GJB2 gene. Van Geel et al. (2002) concluded that KID syndrome and HID syndrome are identical at the molecular level and represent a single clinical entity.