THANATOPHORIC DYSPLASIA WITH STRAIGHT FEMURS AND CLOVERLEAF SKULL
THANATOPHORIC DYSPLASIA WITH KLEEBLATTSCHAEDEL
CLOVERLEAF SKULL WITH THANATOPHORIC DWARFISM
TD2
Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients ... Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients with straight, relatively long femurs always had associated severe cloverleaf skull and were designated TD type II (TD2), whereas TD cases with curved, short femurs with or without cloverleaf skull were designated TD type I (TD1; 187600) (Langer et al., 1987).
Partington et al. (1971) described cloverleaf skull in association with generalized skeletal dysplasia consistent with thanatophoric dwarfism. Two of their 4 cases were in sibs. Horton et al. (1983) reported monozygotic twins with thanatophoric dysplasia who were discordant ... Partington et al. (1971) described cloverleaf skull in association with generalized skeletal dysplasia consistent with thanatophoric dwarfism. Two of their 4 cases were in sibs. Horton et al. (1983) reported monozygotic twins with thanatophoric dysplasia who were discordant for the Kleeblattschaedel anomaly. In a survey of lethal osteochondrodysplasias in the county of Fyn (Funen), Denmark, Andersen (1989) found 2 cases of thanatophoric dysplasia and 1 case of thanatophoric dysplasia with cloverleaf skull. Langer et al. (1987) reported 9 infants with this combination and reviewed 22 previously published cases. In general they concluded that there are 2 types of thanatophoric dysplasia: type I, with curved femora and very flat vertebral bodies; and type II, with straight femora and taller vertebral bodies. Consistent though subtle histopathologic characteristics were thought to differentiate the 2 types. Very few type I cases had cloverleaf skull, and the cloverleaf skull was mild. Almost all type II cases had severe cloverleaf skull. Li et al. (2006) reported a female fetus with TD2 and occipital encephalocele, in whom they identified the K650E mutation in the FGFR3 gene. The authors stated that this was only the second reported case of TD2 with encephalocele.
In 16 individuals with type II thanatophoric dysplasia, Tavormina et al. (1995) identified a heterozygous 1948A-G mutation in the FGFR3 gene, causing a lys650-to-glu (K650E; 134934.0004) substitution in the tyrosine kinase domain.
In a review of ... In 16 individuals with type II thanatophoric dysplasia, Tavormina et al. (1995) identified a heterozygous 1948A-G mutation in the FGFR3 gene, causing a lys650-to-glu (K650E; 134934.0004) substitution in the tyrosine kinase domain. In a review of 91 cases of TD by Wilcox et al. (1998), the K650E mutation was the only cause of TD type II, and occurred in 17 cases (19%).