Compound heterozygosity for the achondroplasia-hypochondroplasia FGFR3 mutations: Prenatal diagnosis and postnatal outcome

We report on a male newborn infant, a compound carrier of heterozygous muta tions in the FGFR3 gene causing achondroplasia and hypochondroplasia, The m other has achondroplasia and carries the common G1138 (G380R) mutation in t he FGFR3 gene; the father has hypochondroplasia due to the C1620A (N540K) m utation in the same gene. The fetus was found to carry both mutations diagn osed prenatally by amniocentesis at 17.6 weeks of gestation, following mate rnal serum screening which showed an increased risk for Down syndrome (1:33 7), Detailed fetal ultrasound studies showed a large head, short limbs, and a small chest at 22 weeks of gestation, The changes were more severe than those of either achondroplasia or hypochondroplasia, The patient was born b y cesarean section at 38 weeks of gestation and had rhizomelic shortness of the upper and lower limbs with excess skin folds, large head, enlarged fon tanelles, frontal bossing, lumbar gibbus, trident position of the fingers, and a narrow chest with a horizontal line of demarcation at the narrowest a rea of the chest, Skeletal radiographs showed shortness of the long bones a nd flare of metaphyses. He had respiratory difficulties and was treated wit h nasal prongs. Seizures developed on day 2 of life and recurred on day 9 a nd responded to treatment with phenobarbital. Brain computed tomographic sc an showed possible grey matter heterotopia, partial agenesis of the corpus callosum, and cortical dysplasia, To our knowledge, there are only two prev iously published cases of compound heterozygous achondroplasia-hypochondrop lasia patients, The diagnosis was confirmed by DNA mutation analysis of the FGFR3 gene in both cases, Am, J. Med. Genet. 84:401-405, 1999, (C) 1999 Wi ley-Liss, Inc.