Edinburgh Malformation Syndrome

A number sign (#) is used with this entry because the phenotype is the result of a chromosomal aberration rather than mutation in a single gene.

Clinical Features

Habel (1974) described an Edinburgh family in which 5 infants (4 females, 1 male) in 4 sibships were found to have consistently abnormal facial appearance, true or apparent hydrocephalus, retardation in motor and mental development, failure to thrive, and death in the first months of life. Unexplained neonatal hyperbilirubinemia and advanced bone age may be features. The affected infants were related as first cousins or first cousins once removed and there was no consanguinity in the family. A carp mouth and hairiness of the forehead suggested the Cornelia de Lange syndrome. A chromosomal abnormality was postulated.

Cytogenetics

Using high-resolution chromosome analysis, Laing et al. (1991) identified a familial reciprocal and apparently balanced translocation between chromosomes 1 and 2 in 3 members of this family, following detection of an unbalanced karyotype in a neonate with an abnormal phenotype similar to that described by Habel (1974). The disorder is caused by trisomy 1q43.3-qter and monosomy of 2q37.1-qter.