Ivic Syndrome

A number sign (#) is used with this entry because of evidence that IVIC syndrome is caused by heterozygous mutation in the SALL4 gene (607343) on chromosome 20q13.

Duane-radial ray syndrome (DRRS; 607323) is an allelic disorder with a similar phenotype.

Nomenclature

The IVIC syndrome, an acronym for Instituto Venezolano de Investigaciones Cientificas, was first described by Arias et al. (1980).

Neri and Sammito (1989) suggested that the IVIC syndrome may represent an 'iceberg dominant' trait, i.e., that because of the wide range of severity typical of dominant traits, mild cases may be recognized. In addition, they proposed oculootoradial syndrome (OORS) as an alternative and perhaps preferable designation.

Clinical Features

Arias et al. (1980) described the IVIC syndrome in 19 living descendants of a Caucasian family that migrated to Venezuela from the Canary Islands in the early 1800s. The disorder could be traced over 6 generations with complete penetrance. There was widely variable expression of a radial ray defect that was sometimes an almost normal thumb and at other times a severely malformed upper limb. When present, the thumb had a long, slender metacarpal and short distal phalanx. The radial carpal bones were always affected. In most cases the extraocular muscles were affected, resulting in strabismus. Hearing was impaired by a mixed congenital loss. Mild thrombocytopenia and leukocytosis were noted. Imperforate anus and kidney malrotation occurred in some.

Sammito et al. (1988) described 3 affected individuals in 2 generations of an Italian family. Autosomal dominant inheritance was confirmed by the occurrence of the syndrome in father and son. A second child was more mildly affected. Czeizel et al. (1989) described a third family, with affected mother and son.

Elcioglu and Berry (1997) described Turkish monozygotic twin girls who were discordant for the IVIC syndrome. One was diagnosed them on the basis of hand abnormalities and hearing loss, whereas her sister had only strabismus. In the family there were at least 7 apparently and 2 possibly affected members over 4 generations; most of these individuals were only mildly affected. The 2 girls, whose monozygosity was proved using several DNA loci, showed marked variability in expression, indicating that modification of expression of the responsible gene must be epigenetic or environmental rather than genetic.

Molecular Genetics

In affected members of the original Venezuelan family reported by Arias et al. (1980), Paradisi and Arias (2007) identified a heterozygous mutation in the SALL4 gene (607343.0013). The authors emphasized the intrafamilial phenotypic variability of the same mutation.