Bazex Syndrome

Description

Bazex syndrome is an X-linked dominant disorder characterized by a triad of congenital hypotrichosis, follicular atrophoderma affecting the dorsa of the hands and feet, the face, and extensor surfaces of the elbows or knees, and the development of basal cell neoplasms, including basal cell nevi and basal cell carcinomas from the second decade onward (Yung and Newton-Bishop, 2005).

Rombo syndrome (180730) has similar features, but shows autosomal dominant inheritance.

Clinical Features

Bazex et al. (1964, 1966) reported a syndrome comprising hypotrichosis, follicular atrophoderma, and multiple basal cell neoplasms.

Parrish et al. (1972) reported a family of Italian origin in which 11 members spanning 3 generations had hypotrichosis with light-colored hair and facial milia. Examination of the hair showed markedly reduced density of scalp hair and decreased melanization of the hair shaft. Parrish et al. (1972) postulated a defect in the induction phase of hair development during fetal life. There was no male-to-male transmission, but 1 affected man had a normal daughter, arguing against X-linked dominant inheritance. However, Kidd et al. (1996) suspected that the family reported by Parrish et al. (1972) had a variant of Bazex-Dupre-Christol syndrome.

Viksnins and Berlin (1977) described a kindred in which 8 persons in 3 generations had the condition described by Bazex et al. (1964, 1966) in 6 members of a family. Affected persons had lesions suggesting 'multiple ice-pick marks' on the dorsum of the hands and elbows dating from early infancy and basal cell carcinomas that developed on the face between ages 15 and 26 years. The authors stated that 'follicular atrophoderma,' although a well-established term, was not appropriate because histologic studies did not show atrophy. Hypotrichosis was also present in the cases of Bazex et al. (1964).

Gould and Barker (1978) described affected individuals in 4 generations of a British family. Prominent pitting of the skin on the face and back of the hands was noted, as well as hypotrichosis in 2 patients studied. Hairs had a twisted and flattened appearance on scanning electron microscopy. There was no instance of male-to-male transmission and the only affected male in the family had an unaffected son.

Yung and Newton-Bishop (2005) reported follow-up of the family reported by Gould and Barker (1978). There was a total of 11 affected members spanning 6 generations. The patient was a 3-year-old girl who was the granddaughter of the original proband reported by Gould and Barker (1978). She presented at age 2 years with multiple brown asymptomatic papules over the genital area and medial aspect of the thighs. She had hypotricha since birth, and prominent facial milia and follicular atrophoderma of the cheeks consistent with Bazex-Dupre-Christol syndrome. Skin biopsy from the genital region of the patient showed multiple benign trichoepitheliomas, which arise from cells derived from the hair follicle. The patient's mother had facial milia, follicular atrophoderma of the cheeks and dorsa of the hands, hypotricha since birth, hypohidrosis, and axillary hidradenitis suppurativa. The patient's newborn brother also had features of the syndrome. Yung and Newton-Bishop (2005) noted that trichoepitheliomas and hidradenitis suppurativa had not previously been described in Bazex syndrome.

Oley et al. (1992) reported an Australian family of Italian origin in which 9 individuals in 4 generations and 6 sibships had basal cell carcinomas, coarse and sparse scalp hair, sparse body hair, excessive sweating, and multiple milia on face and limbs during childhood. One 32-year-old patient with multiple milia over her face had markedly increased pigmentation of the face, particularly around the eyes. Beginning at the age of 22, she had about 20 basal cell carcinomas removed. Since there was no instance of male-to-male transmission, the pedigree was consistent with either autosomal dominant or X-linked dominant transmission. All 3 daughters of 2 males who had children were affected. Vabres and de Prost (1993) concluded that the family reported by Oley et al. (1992) had Bazex syndrome. They noted that the presence or absence of follicular atrophoderma was not mentioned by Oley et al. (1992) but pointed out that 'this manifestation may be undiagnosed, even by experienced dermatologists, if not carefully sought.'

Rapelanoro et al. (1994) reported a 30-month-old boy with coarse, sparse hair and multiple milia on the face, chest, axillae, and pubic region. A sister, aged 16 years, had apparently normal scalp, axillary, and pubic hair, but had had coarse and very sparse scalp hair and multiple milia on the face and limbs in childhood. Most of the milia disappeared at puberty; a few persisted on the forehead. The same manifestations were present in the mother from birth and disappeared at 40 years of age. There were no abnormalities of teeth and nails. Polarizing light microscopy showed an increased diameter of the hair shaft. Family history revealed that the condition affected at least 20 individuals, both males and females, spanning 4 generations. There was no transmission from an unaffected parent, and no male-to-male transmission was observed, consistent with either autosomal or X-linked dominant inheritance.

Lacombe and Taieb (1995) examined 17 members of the family reported by Rapelanoro et al. (1994) and affirmed striking intrafamilial phenotypic variability consistent with Bazex syndrome. In 3 of 8 patients, follicular atrophoderma on the back of the hand was found in addition to hypertrichosis and milia, and 2 patients had been treated for basal cell carcinoma. They concluded that the same family had been reported by Le Coulant et al. (1967). Doubts had been raised at that time concerning the X-linked mode of inheritance of Bazex syndrome because of an instance of male-to-male transmission in the pedigree, but Lacombe and Taieb (1995) found that the suspected affected male was in fact unaffected, thus confirming X-linked dominant inheritance.

Kidd et al. (1996) described a Scottish family with typical manifestations of Bazex syndrome and reviewed 15 previously reported families with approximately 120 affected persons. The authors noted that 'pinched' nose with hypoplastic alae and prominent columella may be another characteristic manifestation of the disorder.

Inoue et al. (1998) found reports of a total of 125 patients in 20 pedigrees. The disorder had been reported chiefly in France, and all of the patients were Caucasians.

Inheritance

Viksnins and Berlin (1977) suggested X-linked dominant inheritance in Bazex syndrome because no male-to-male transmission had been reported. In their family, all 3 daughters of an affected male, but none of his sons, were affected.

Vabres and de Prost (1993) noted that Pierard et al. (1971) and Gould and Barker (1978) favored X-linked dominant inheritance, and stated that the pedigree pattern described by Oley et al. (1992) was consistent with X-linked dominant inheritance.

The report of Rapelanoro et al. (1994), with follow-up by Lacombe and Taieb (1995), also indicated that Bazex syndrome shows X-linked dominant inheritance.

Mapping

Using microsatellite markers of the X chromosome in 3 families with Bazex syndrome, Vabres et al. (1995) found evidence for X-linkage and regional assignment to chromosome Xq24-q27. The maximum lod score was 5.26 at theta = 0 with the DXS1192 locus.