Co-occurrence of achondroplasia and Down syndrome: genotype/phenotype association

Abstract

BACKGROUND: This report describes the sixth case of an unusual association: Down syndrome with achondroplasia. It also analyzes the effects of both of these disorders on patient phenotype. METHODS: A male infant was evaluated for Down syndrome. His appearance also suggested a diagnosis of achondroplasia. The child was evaluated by physical examination, radiography, cytogenetic study, and mutation analysis. RESULTS: Chromosome analysis showed a karyotype of 47,XY,+21 in all 30 cells analyzed. Radiographic examination showed typical findings of achondroplasia, such as disproportionately large skull, shortening of limb segments, and lumbar lordosis. FGFR3 screening showed a heterozygous G1138A mutation. CONCLUSIONS: The interaction of these two distinct genetic disorders in the same patient produces a phenotype typical of each syndrome with some overlapping signs. This case represents de novo origin of two disorders that both may be parental-age related. Birth Defects Research (Part A) 2010. © 2010 Wiley-Liss, Inc.