Curry-Jones Syndrome

A number sign (#) is used with this entry because of evidence that Curry-Jones syndrome (CRJS) is caused by somatic mosaic mutation in the SMOH gene (601500) on chromosome 7q32.

Description

Curry-Jones syndrome is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas (summary by Twigg et al., 2016).

Clinical Features

Temple et al. (1995) described 5 unrelated children (3 males and 2 females) with the association of cranial defects, polysyndactyly, and defects of the skin and gastrointestinal tract. (The patients included the first reported case presented by Curry at the 1987 David W. Smith Workshop on Malformations and Morphogenesis and a similar patient described by Jones (Cohen, 1988; Gorlin et al., 1990), leading to the designation Curry-Jones syndrome.) Unilateral craniosynostosis and shortness of the base of the skull caused striking asymmetry of the face with narrow palpebral fissures. Complete absence of the corpus callosum was found in 1 patient and patial absence in 2. One of the male infants had coloboma, and another had microphthalmia. All patients had preaxial polydactyly and syndactyly of the hands and/or feet. Multiple gastrointestinal myofibromata were found in 2 children, one of whom also had anal stenosis. All 5 had abnormal skin with areas of atrophy, although dermatologic manifestations were different in all the cases. None of the parents in these families were consanguineous, and there were no affected relatives.

Thomas et al. (2006) described a 4-year-old boy with a mild form of Curry-Jones syndrome with no significant craniofacial, developmental, or gastrointestinal problems.

Grange et al. (2008) reported 2 patients with Curry-Jones syndrome who had previously unreported features; one had multiple intraabdominal smooth muscle hamartomas and trichoblastoma of the skin, and the other was born with occipital meningoceles and developed a desmoplastic medulloblastoma. Based on an association of trichoblastoma with basal cell carcinoma and of desmoplastic medulloblastoma with nevoid basal cell carcinoma syndrome (109400) and PTCH (601309) mutations, the authors suggested that Curry-Jones syndrome may be caused by mutation in genes in the Sonic hedgehog (SHH) signaling pathway (see 600725). Molecular analysis in their patients excluded mutation in the PTCH and GLI3 (165240) genes.

Clinical Variability

Mingarelli et al. (1999) described a boy with microcephaly, brachycephaly, bifid halluces with osseous syndactyly of bifid proximal phalanges and bifid distal phalanges, bilateral ptosis of eyelids, bilateral horizontal nystagmus, microcornea, cataract and colobomas affecting iris, inferior choroids, and extending throughout the optical nerves, and several linear areas of skin depigmentation in the lumbar region. Mingarelli et al. (1999) noted phenotypic overlap with Curry-Jones syndrome but suggested that the features in their patient represented a 'new' syndrome.

Molecular Genetics

Twigg et al. (2016) studied tissue samples from 10 unrelated patients with Curry-Jones syndrome, including 6 previously reported patients (Temple et al., 1995; Thomas et al., 2006; Grange et al., 2008). They identified somatic mosaicism for the identical missense mutation in the SMOH gene (L412F; 601500.0003) in tissues from 8 of the patients, including the 2 originally described by Curry and Jones. The mutant allele, which was present at levels substantially below 50% in the samples, was not reliably detected in blood or saliva samples; thus, detection of mosaic mutations in CRJS may require analysis of affected skin and tissue from internal organs. Given the widespread mosaicism in CRJS, Twigg et al. (2016) suggested that it arises postzygotically early during embryonic dvelopment.