Microphthalmia, Syndromic 8

Clinical Features

Viljoen and Smart (1993) described a woman with mental retardation, borderline microcephaly, microphthalmia, prognathism, cleft lip and palate, ectrodactyly of the feet, and premature aging of the skin. Her karyotype showed a de novo translocation 46,XX,t(6;13)(q21;q12).

Suthers and Morris (1996) reported a mentally retarded man with borderline microcephaly, microphthalmia, microcornea, prognathism, wide gap between his upper central incisors, ventricular septal defect, split-feet, cryptorchidism, and normal karyotype. They proposed that their patient and that of Viljoen and Smart (1993) represented a distinct syndrome which could be related to mutation in a gene located on either 6q21 or 13q12.

Van den Ende et al. (1996) described the association of congenital heart defects and split-feet in 4 infants who had the additional manifestations of short palpebral fissures and micrognathia; see 601348. It is possible that the various facial abnormalities reflect age-related differences.

Cytogenetics

In the patient with MMEP and translocation 46,XX,t(6;13)(q21;q12) reported by Viljoen and Smart (1993), Vervoort et al. (2002) localized the breakpoint on chromosome 6q21 close to marker D6S1250. Cloning of the breakpoint fragment allowed localization of the der(13) breakpoint close to a marker in the region 13q11-q12. Sequencing of the chromosome 13 breakpoint confirmed that the translocation was balanced, with no missing or duplicated material. No gene on chromosome 13 appeared to be disrupted, whereas the SNX3 gene on 6q21 was. Mutation screening of another sporadic case of MMEP failed to detect any point mutations or deletions in the SNX3 coding sequence. Because of the possibility of positional effect, Vervoort et al. (2002) suggested that another candidate gene in the vicinity of the chromosome 6 breakpoint may have been responsible for MMEP in the original patient or, just as likely, the MMEP phenotype in the 2 patients resulted from different genetic causes.