Achondroplasia and thanatophoric dwarfism in the newborn

Abstract

Out of a total of 64,000 births in St. Mary's Hospital, Manchester, 17 were originally diagnosed as having achondroplasia. When the diagnosis was reviewed, 10 of these infants proved to be thanatophoric dwarfs, 3 had inherited achondroplasia, 1 was apparently a mutant achondroplastic, while 3 others had other forms of non‐achondroplastic chondrodystrophy. All 10 thanatophoric dwarfs but only one other child in the series were still‐born. It is concluded that both the birth rate and the perinatal mortality rate for achondroplasia are much lower than was previously believed. The clinical features of 10 infants with thanatophoric dwarfism in this series are reviewed and a high incidence of associated defects noted. There was an excess of affected males and one pair of affected sibs occurred suggesting autosomal recessive inheritance, with sex‐limitation or early loss of female embryos, in thanatophoric dwarfism. The implications of this diagnostic heterogeneity are important in counselling parents of apparently achondroplastic infants. The necessity for postulating a high mutation rate to the achondroplasia gene depended upon the assumption that about 80% of such infants died. The results reported here have suggested that most of this mortality is accounted for by thanatophoric dwarfs and consequently it is no longer necessary to postulate a mutation rate greater than 1:100,000 at most in achondroplasia.