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

Abstract

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, del(2)(q24.3q31.3), respectively). The first child had severe learning difficulties, growth retardation, unilateral ptosis, small palpebral fissures, a cleft uvula, and bilateral cutaneous syndactyly of the second and third toes. Despite her male karyotype, she had female external genitalia with hypoplasia of the clitoris and labia minora. This is the first reported case of feminization of the external genitalia in a genotypic male with an interstitial deletion of chromosome 2q31 and adds to the growing amount of evidence for a gene involved in sex determination in this chromosome region. The second child had severe mental and growth retardation, ptosis, down-slanting palpebral fissures, low-set ears, micrognathia, finger camptodactyly, and brachysyndactyly of the second to fifth toes. The clinical manifestations associated with deletions of 2q31 to 2q33 are similar to those found with proximal deletions at 2q24 to 2q31 and of band 2q24, suggesting that the phenotype may result from haploinsufficiency for one or more genes located at 2q31. Microsatellite 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.