Robinow-Sorauf Syndrome

A number sign (#) is used with this entry because Robinow-Sorauf syndrome is caused by heterozygous mutation in the TWIST gene (601622.0009). Some authors (e.g., Reardon and Winter, 1994) have suggested that the disorder is not distinct, but part of the phenotypic spectrum of Saethre-Chotzen syndrome (101400), which is also caused by TWIST mutations.

Clinical Features

Carter et al. (1982) and Young and Harper (1982) described a distinct acrocephalosyndactyly syndrome that the first group of authors suggested be called the Robinow-Sorauf syndrome in recognition of the priority of description by those authors (Robinow and Sorauf, 1975). The patients were described by Carter et al. (1982) as having facies like those of the Saethre-Chotzen syndrome and bilaterally broad big toes owing to partial or complete duplication of the distal phalanx. The syndrome was considered distinct from the Pfeiffer syndrome (101600) in which the facies more nearly resembles Crouzon syndrome (123500) and in which the proximal phalanx of the big toe (and often of the thumb) is abnormal. Two instances of male-to-male transmission were noted in the family reported by Young and Harper (1982).

Reardon and Winter (1994) reviewed observations leading them to suggest that it is 'unlikely that there is continued justification' for affording the Robinow-Sorauf syndrome an entry separate from that for Saethre-Chotzen syndrome.

Molecular Genetics

In a proband and his mother affected with Robinow-Sorauf syndrome, Kunz et al. (1999) reported a frameshift mutation in the TWIST gene (601622.0009). The authors considered this mutation to be confirmation that the Saethre-Chotzen and Robinow-Sorauf syndromes are at least allelic, if not part of a clinical spectrum of the same condition. Cai et al. (2003) suggested that the diagnosis of Robinow-Sorauf syndrome in the family reported by Kunz et al. (1999) could be questioned because the affected individuals lacked certain characteristics, such as syndactyly, that were found repeatedly in all members of the original Robinow-Sorauf pedigree.

Cai et al. (2003) studied the original family reported by Robinow and Sorauf (1975) and found that the affected individuals were heterozygous for a 221C-T transition in the TWIST gene, resulting in a premature stop codon at amino acid position 71 (Q71X; 180750.0012). This novel nonsense mutation was 5-prime of the DNA-binding region where other nonsense mutations had been found in families with Saethre-Chotzen syndrome. Cai et al. (2003) stated that they examined 3 of the 11 affected members of the original family in addition to the propositus and found that all had second interdigital syndactyly as well as a toe deformity (either polydactyly or hallux valgus). Cai et al. (2003) stated that the reported 'Robinow-Sorauf' families are examples of variable expression of the TWIST mutant phenotype and provide further proof that the 'Robinow-Sorauf' syndrome lies within the spectrum of the SCS syndrome.