Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: analysis of 13 patients with a de novo deletion

We performed clinical, cytogenetic, and molecular analyses on 13 patients ( 8 females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn synd rome due to de novo deletions of chromosome 4p. All patients presented with the typical facial gestalt, microcephaly, and profound mental retardation. Other clinical signs were low birth weight (10/13; 77%), postnatal short s tature (8/12; 66%), muscular hypotonia (12/13; 92%), seizures (11/13; 85%), congenital heart defects (4/13; 31%), colobomata of iris (4/12; 33%), geni tal anomalies (4/13; 31%), deafness (3/13; 23%), and renal anomalies (3/13; 23%). The smallest deletion was a submicroscopic terminal deletion of near ly 2.5 Mb. The largest was a terminal deletion of nearly 30 Mb. Cleft lip/p alate, preauricular pits/tags, and congenital heart defects were present on ly in patients with terminal deletions larger than 10Mb. The deviations fro m mean birth weight, birth length, and postnatal head circumference correla ted with the size of the deletion. Determining the parental origin of the d eletion with microsatellite markers, the maternal allele was missing in thr ee patients and the paternal allele in eight patients. Our observations sup port the existence of a partial genotype-phenotype correlation in Wolf-Hirs chhorn syndrome.