NeurometPlus

Incidence

Isolated cases. Listed in OMIM in the autosomal dominant catalog, but most cases are believed to be sporadic. Deletion 4p16 is believed to be sufficient for the full expression of this syndrome. Some cases show a de novo terminal deletion.

Clinical Characteristics

The Wolf-Hirschhorn syndrome, caused by partial deletion of the short arm of chromosome 4, is characterized by severe growth retardation and mental defect, microcephaly, \'Greek helmet\' facies, and closure defects (cleft lip or palate, coloboma of the eye, and cardiac septal defects). Partial deletion of the short arm of chromosome 4 with severe psychomotor deficiency and abnormalities of the craniofacial structures, heart, kidneys, and other organs. The most common defects include asymmetric skull, microcephaly, high forehead, beaked nose, hypertelorism, epicanthal folds, and prominent glabella. The phenotype of proximal interstitial deletion (del4p15) differs from that in the Wolf-Hirschhorn syndrome and is characterized by distinct facies, multiple minor congenital anomalies, psychomotor retardation and normal growth. Deletion 4p15-16 is expressed in a different phenotype which includes long face, midface hypoplasia, upslanted palpebral fissures, epicanthal folds, large beaked nose, highly arched palate, thick lower lip, micrognathia, broad and short neck, broad hands and feet, tall and thin habitus, delayed growth and mental development, and hypotonia.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

Karyotype. Partial deletion of short arm of chromosome 4 (4p-). de novo deletions in 8% of patients (preferentially paternally derived). 13% of cases secondary to familial translocation (often maternally derived). Size of deletion varies from cytogenetically visible deletions to undetectable cytogenetic deletions. FISH can be used to detect deletions of 4p16.3, the critical region for the phenotype.