Further clinical & cytogenetic delineation in Ip36 deletion syndrome

Abstract

Deletion of Ip36 has recently been recognized as an apparently common new chromosomal syndrome. Aproximately 30 patients with pure Ip36 deletion have been described to date (J Med Genet 1999;36:657-663). Patients show hypotonia and moderate to severe developmental delay with speech usually more severely affected than motor development. Common dysmorphic features include a large anterior fontanelle, prominent forehead, deep set eyes, midface hypoplasia, small mouth and pointed chin. Orofacial clefting, cardiac, ophtalmologic, and auditory abnormalities have also been observed in a proportion of patients. With regard to growth pattern, there seems to be two separate phenotypes. While most affected children show postnatal growth retardation, some patients develop obesity and hyperphagia resembling Prader-Willi syndrome. Also, although epilepsy has been observed in the majority of patients (with variable seizures patterns), some children present only with transient seizures in infancy, sometimes without EEG abnormalities. The discrepancies in the phenotype apparently do not seem to be easily correlated with extension of the deletion or parental origin. We have had the opportunity to study four unrelated cases of pure de novo Ip36 deletions. All of them showed only one copy of the FISH probe DIZ2, located at Ip36. In one of the patients the deletion was not visible in high resolution preparations. FISH studies have excluded cryptic balanced translocations. The four patients showed similar phenotype with a large anterior fontanelle, long straight eyebrows, deep set eyes, small mouth with downturned corners, pointed chin and, transient seizures in infancy. The two older patients developped obesity and hyperphagia after 3-4 years, resembling Prader-Willi syndrome. They also share identical patterns of developmental delay (severe speech delay in spite of moderate developmental delay). One may speculate that the Ip36 deletion patients that eventually develop obesity might also represent the subset of patients with transient seizures and less severe developmental delay. The use of microsatellites that map to Ip36 is currently underway to determine the extent of the deletion, as well the parental origin of the deleted segment.