Mental retardation in a child with a {open_quotes}de novo{close_quotes} deletion of terminal 14q and a family history of dyslexia

A couple presented for prenatal diagnosis for advanced maternal age. A review of the family history revealed that their elder daughter was mentally retarded while their second daughter was of normal intelligence. The father and his brother were both dyslexic. The paternal grandmother had lost three pregnancies, all female. The elder daughter had been fully assessed in the past, but no diagnosis had been made. During her first few years, she was frequently ill and failed to thrive. A developmental assessment at age 5 years concluded that she was moderately mentally retarded. She was minimally dysmorphic. DNA testing for fragile X and urine amnio acids, organic acids and metabolic screen were negative. Chromosome and FISH analyses revealed a satellited 14q with a deletion of 14q32.3. Parents did not show the karyotypic changes, but FISH studies on them and the dyslexic uncle are pending. A molecular work-up of chromosome 14 in this family is also in progress. In this child, the phenotype is probably related to the cytogenetic findings. The information about 14q terminal deletions in the literature is limited but a fairly consistent phenotype, which is slightly different from ring 14, is emerging. This is more obvious in infants that more » in older children. The family history of dyslexia could be unrelated to our patient`s findings but it is also possible that there is a recessive gene for dyslexia in this family which maps to 14q32.3. The current molecular map of this area provides no answer to this question. Genes mapped to 14q3.3 include the alpha-1-antitrypsin gene, the brain component of creative kinase (CKB) and the immunoglobulin heavy chain genes. Loss of heterozygosity of 14q has been associated with end stage human neuroblastoma and colonic neoplasia. « less