CHROMOSOME 1P36 DELETIONS - THE CLINICAL PHENOTYPE AND MOLECULAR CHARACTERIZATION OF A COMMON NEWLY DELINEATED SYNDROME

Deletions of the distal short arm of chromosome 1 (1p36) represent a c ommon, newly delineated deletion syndrome, characterized by moderate t o severe psychomotor retardation, seizures, growth delay, and dysmorph ic features. Previous cytogenetic underascertainment of this chromosom al deletion has made it difficult to characterize the clinical and mol ecular aspects of the syndrome. Recent advances in cytogenetic technol ogy, particularly FISH, have greatly improved the ability to identify 1p36 deletions and have allowed a clearer definition of the clinical p henotype and molecular characteristics of this syndrome. We have ident ified 14 patients with chromosome 1p36 deletions and have assessed the frequency of each phenotypic feature and clinical manifestation in th e 13 patients with pure 1p36 deletions. The physical extent and parent al origin of each deletion were determined by use of FISH probes an cy togenetic preparations and by analysis of polymorphic DNA markers in t he patients and their available parents. Clinical examinations reveale d that the most common features and medical problems in patients with this deletion syndrome include large anterior fontanelle (100%), motor delay/hypotonia (32%), moderate to severe mental retardation (92%), g rowth delay (85%), pointed chin (80%), eye/vision problems (75%), seiz ures (72%), flat nasal bridge (65%), clinodactyly and/or short fifth f inger(s) (64%), low-set ear(s) (53%), ear asymmetry (57%), hearing def icits (56%), abusive behavior (56%), thickened ear helices (53%), and deep-set eyes (50%). FISH and DNA polymorphism analysis showed that th ere is no uniform region of deletion but, rather, a spectrum of differ ent deletion sizes with a common minimal region of deletion overlap.