Three unrelated boys with a new multiple congenital anomaly-mental retardation syndrome are reported from the University of Minnesota Medical School, and the Universita Degli Studi di Pisa, Italy. Congenital abnormalities included 1) bilateral periventricular nodular heterotopia (BPNH) and ventriculomegaly, 2) cortical dysplasia, 3) cerebellar hypoplasia, 4) severe mental retardation, 5) epilepsy, 6) clinodactyly, 7) syndactyly, and 8) probable X-linked inheritance. Involvement of the same Xq28 locus as found in classical, isolated BPNH was suggested. [1]

COMMENT. In contrast to this new multiple congenital anomaly-mental retardation syndrome described by Dobyns et al, the classical BPNH syndrome of bilateral periventricular nodular heterotopia with epilepsy affects mainly girls with normal intelligence. One gene associated with classical BPNH is mapped to chromosome Xq28, similar to the finding in one case of Dobyns syndrome. Other syndromes associated with BPNH include: 1) BPNH with Ehler-Danlos Syndrome, in females with normal intelligence; and 2) BPNH with frontonasal dysplasia, with nephrosis, the short-gut syndrome, and Vles agenesis of the corpus callosum syndrome, all affecting males with mental retardation, as in Dobyns syndrome. Most have X-linked inheritance patterns, and 3 are localized to Xq28. (see Sarnat HB, in Progress in Pediatric Neurology III, 1997;pp365-369, for reference to X-linked periventricular heterotopia and markers in the distal Xq28 locus).