DELETION OF CHROMOSOME-21 IN A GIRL WITH CONGENITAL HYPOTHYROIDISM AND MILD MENTAL-RETARDATION

We report on a girl with a large interstitial deletion of the long arm of chromosome 21 and with mild mental retardation, congenital hypothy roidism, and hyperopia, The deletion [del(21)(q11.1-q22.1)] extends mo lecularly from marker D21S215 to D21S213, The distal breakpoint is not clearly defined but is situated between markers D21S213 and IFNAR, Th is patient has the largest deletion of chromosome 21 known without hav ing severe mental retardation or malformations, The deletion does not involve the ''Down syndrome chromosome'' region, the region of chromos ome 21 which in trisomy causes most of the manifestations of Down synd rome. Apparently, the proximal part of the long arm of chromosome 21 d oes not include genes that are responsible for severe clinical effects in the event of either deletion or duplication, since several reporte d patients with either trisomy or deletion of this region have mild ph enotypic abnormalities, Congenital hypothyroidism is much more common in Down syndrome than in the average population, Thus, the congenital hypothyroidism of the present patient might indicate that there is one or several genes on the proximal part of chromosome 21, which might b e of importance for the thyroid function. (C) 1996 Wiley-Liss, Inc.