Partial monosomy of chromosome 1p36.3: Characterization of the critical region and delineation of a syndrome

We describe 5 patients ranging in age from 3 to 47 years, with karyotypic abnormalities resulting in monosomy for portion of 1p36.3, microcephaly, mental retardation, prominent forehead, deep-set eyes, depressed nasal bridge, flat midface, relative prognathism, and abnormal ears. Four patients have small hands and feet. All exhibited self-abusive behavior. Additional findings in some of the patients include brain anomalies, optic atrophy, hearing loss and skeletal deformities. The breakpoints within chromosome 1 were designated at 1p36.31 (3 cases), 1p36.32 (1 case) and 1p36.33 (1 case). Thus, the smallest region of deletion overlap is 1p36.33→1pter. Detection of the abnormal 1 relied on high resolution G-band analysis. Fluorescence in situ hybridization (FISH) utilizing a DNA probe (Oncor D1Z2) containing the repetitive sequences in distal 1p36, confirmed a deletion of one 1 homologue in all 5 cases. The abnormal 1 resulted from a de novo deletion in only one patient. The remaining patients were either confirmed (3 cases) or suspected (1 case) to have unbalanced translocations. Despite the additional genetic imbalance present in these four cases, monosomy of 1p36.33 appears to be responsible for a specific clinical phenotype. Characterization of this phenotype should assist in the clinical diagnosis of this chromosome abnormality.