Schopf-Schulz-Passarge Syndrome

A number sign (#) is used with this entry because of evidence that Schopf-Schulz-Passarge syndrome (SSPS) is caused by homozygous mutation in the WNT10A gene (606268) on chromosome 2q35.

Clinical Features

Schopf et al. (1971) described keratosis palmoplantaris with hypodontia, hypotrichosis, and cysts of the eyelids in sisters whose parents were first cousins. The deciduous teeth were lost early and the permanent dentition in 1 patient consisted only of 2 incisors and a molar. Palmoplantar keratosis and fragility of the nails began at about age 12. At age 25, head hair became sparse and body hair was lost completely. Cysts of both upper and lower eyelids were noted at age 60. The cysts were thought to be derived from the glands of Moll.

Font et al. (1986) reported a family with 3 affected brothers who showed manifestations fairly similar to those in the family reported by Schopf et al. (1971). However, whereas Schopf et al. (1971) thought that their patients might have Papillon-Lefevre syndrome (245000), Font et al. (1986) concluded that both families had a separate disorder, which is distinguished by the occurrence of apocrine hidrocystomas of the eyelid margins.

Monk et al. (1992) described an English family in which a 62-year-old woman and her 58-and 51-year-old brothers had what the authors referred to as the Schopf-Schulz-Passarge syndrome. They found previous reports of only 8 cases, including those of Burket et al. (1984), Nordin et al. (1988), and Perret (1989). The woman reported by Monk et al. (1992) had thickening of the skin of her palms and soles for 15 years and had had a hypernephroma and a basal cell carcinoma of the skin. Abnormality of deciduous teeth had been noted on school examination and no secondary teeth had ever erupted. She had scanty scalp hair and the fingernails were hypoplastic. The eyelid margins of both eyes showed numerous cysts 1-2 mm in diameter, some clear and others showing a milky opacity. The brothers had essentially identical findings. One of the sibs had an unaffected son.

Stevens et al. (1996) provided a comprehensive classification of the primary palmoplantar keratodermas. Where more than a single ectodermal structure was involved, as in this condition, they coined the term 'palmoplantar ectodermal dysplasia' to emphasize the generalized nature of the disorder. They further identified a total of 19 subtypes, the Schopf-Schultz-Passarge syndrome being type XIX.

Gorlin (1997) concluded that eccrine tumors with ectodermal dysplasia as described by Nordin et al. (1988) is in fact Schopf syndrome. Among the 8 children of normal parents, Nordin et al. (1988) observed 2 brothers and a sister with ectodermal dysplasia manifested by hypodontia, onychodystrophy, trichodysplasia, and palmoplantar keratosis. In addition, a diffuse palmoplantar eccrine hyperplasia, as well as tumors and cysts of eccrine origin, was noted. The parents were not known to be consanguineous. All 3 affected sibs, in their 70s or 80s, had children, and 2 of them had grandchildren, all unaffected. Eccrine glands, also known as exocrine glands, include the sweat glands. Excessive sweating of the hands and feet was described. One of the patients had a cauliflower-like tumor on the heel, with secretions that stained the coverings of the heel. In later years the patients developed nodules on the bodies of the upper and lower eyelids. Eyelashes and eyebrows were sparse, but scalp and body hair was described as unremarkable.

Craigen et al. (1997) stated that 10 cases of this syndrome had been reported; all were compatible with autosomal recessive inheritance except for the family reported by Kuster and Hammerstein (1992), which exhibited dominant inheritance. They reported a family in which 3 full sibs and 1 half sib, all males, had Schopf-Schultz-Passarge syndrome. The half sibs shared a father. The 4 affected males had a total of 8 sons and 4 daughters, none of whom were affected. Craigen et al. (1997) presented photographs of the eyelid cysts, nail dystrophy, and dry erythematous palm of 1 of the patients.

Mallaiah and Dickinson (2001) presented a photo essay of eyelid cysts, plantar hyperkeratosis, dysplastic toenails, and adontia in sibs in their sixth decade who had become symptomatic in their third decade. Histopathology of apocrine hidrocystomas was included. Additionally, the authors commented that simple excision of eyelid cysts was rarely adequate and that en bloc excision of the anterior lamella of the eyelids might be beneficial.

Molecular Genetics

In a female patient with cysts of the eyelids in addition to hypodontia, hypotrichosis, hyperhidrosis, palmoplantar hyperkeratosis, and dystrophic nails, who was negative for mutation in the ectodysplasin-A gene (EDA; 300451), Bohring et al. (2009) identified homozygosity for a nonsense mutation in the WNT10A gene (606268.0001). They also found homozygous or compound heterozygous WNT10A mutations in 8 patients with odontoonychodermal dysplasia (OODD; 257980) but no eyelid cysts. The proband with SSPS had 2 brothers who were heterozygous for the mutation and exhibited dental anomalies: one had agenesis of both lower central incisors, and the other had anomalies of the upper lateral permanent incisors. The proband was also diagnosed with a porocarcinoma of the left heel.