Two cases with interstitial deletions of chromosome 2 and sex reversal in one

We present two children with de novo interstitial deletions of the long arm of chromosome 2 (karyotypes 46,XY, del(2)(q31.1q31.3) and 46,XY, de1(2)(q2 4.3q31.3), respectively). The first child had severe learning difficulties, growth retardation, unilateral ptosis, small palpebral fissures, a cleft u vula, and bilateral cutaneous syndactyly of the second and third toes. Desp ite her male karyotype, she had female external genitalia with hypoplasia o f the clitoris and labia minora. This is the first reported case of feminiz ation of the external genitalia in a genotypic male with an interstitial de letion of chromosome 2q31 and adds to the growing amount of evidence for a gene involved in sex determination in this chromosome region. The second ch ild had severe mental and growth retardation, ptosis, down-slanting palpebr al fissures, low-set ears, micrognathia, finger camptodactyly, and brachysy ndactyly of the second to fifth toes. The clinical manifestations associate d with deletions of 2q31 to 2q33 are similar to those found with proximal d eletions at 2q24 to 2q31 and of band 2q24, suggesting that the phenotype ma y result from haploinsufficiency for one or more genes located at 2q31. Mic rosatellite marker studies showed that both children had paternally derived deletions that included the HOXD gene cluster and the EVX2, DLX1, and DLX2 genes known to be important in limb development. Am. J. Med. Genet. 86:75- 81, 1999. (C) 1999 Wiley-Liss, Inc.