Craniosynostosis, Adelaide Type

Clinical Features

Ades et al. (1994) described a southern Australian kindred with a form of craniosynostosis initially thought to represent the Jackson-Weiss syndrome (123150). They found in the hands coned epiphyses, distal and middle phalangeal hypoplasia, and carpal bone malsegmentation and in the feet coned epiphyses, hallux valgus, phalangeal, tarsonavicular and calcaneonavicular fusions.

Mapping

By linkage mapping in the family described by Ades et al. (1994), Hollway et al. (1995) excluded allelism to Saethre-Chotzen syndrome (101400) at 7p21, craniosynostosis type 2 (CRS2; 604757) at 5q34-q35, Jackson-Weiss and Crouzon (CFD1; 123500) syndromes at 10q24-q25, and Pfeiffer syndrome (101600) mapping near 8cen. Exclusion mapping was extended to the entire genome until linkage to chromosome 4 was detected. A maximum 2-point lod score of 6.2 (theta = 0.0) was obtained with D4S412. The gene for this disorder, which they called 'craniosynostosis Adelaide type,' was localized to 4p16, telomeric to D4S394. The region contains 2 plausible candidate genes: MSX1 (142983) and FGFR3 (134934); the latter gene is mutant in achondroplasia, hypochondroplasia, and thanatophoric dysplasia. Craniosynostosis of the cloverleaf type is present in some cases of thanatophoric dysplasia.