he FGFR3 chondrodysplasias include achondroplasia and thanatophoric dysplasia. Achondroplasia, also called heterozygous achondroplasia, is the most common nonlethal skeletal dysplasia. An impressive 98 percent of cases are due to a speciic point mutation in the FGFJ gene. It has an autosomal dominant inheritance, and 80 percent of cases result from a new mutation. Achondroplasia is characterized by long bone shortening that is predominantly rhizomelic, an enlarged head with frontal bossing, depressed nasal bridge, exaggerated lumbar lordosis, and a trident configuration of the hands. Intelligence is typically normal. Sonographically, the femur and humerus measurements may not lie below the 5th percentile until the early third trimester. hus, this condition is usually not diagnosed until late in pregnancy. In homozygotes, which represent 25 percent of the ofspring of heterozygous parents, the condition is characterized by greater long bone shortening and is lethal.
he other major class of FGFR3 dysplasias, thanatophoric dysplasia, is the most common lethal skeletal disorder. It is characterized by severe micromelia, and afected fetuses-particularly those with type II-may develop a characteristic cloverleaf skull deformity (Kleeblattschade) due to craniosynostosis. More than 99 percent of cases may be con firmed with genetic testing.
Osteogenesis impeecta represents a group of skeletal dysplasias typiied by hypomineralization. here are multiple types, and more than 90 percent of cases are characterized by a mutation in the COLIAI or COLIA2 gene. Type IIa, also called the perinatal form, is lethal. It displays a profound lack of skull ossification, such that gentle pressure on the maternal abdomen from the ultrasound transducer results in visible skull deformation 10-46).
FIGURE 10-46 Osteogenesis imperfecta. Type Ila, which is lethal, is characterized by such profound lack of skull ossification that gentle pressure on the maternal abdomen from the ultrasound transducer results in visible deformation (flattening) of the skull (arrowheads).
Other features include multiple in-utero fractures and ribs that appear "beaded." Inheritance is autosomal dominant, such that all cases result from either new mutations or gonadal mosaicism (Chap. 13, p. 264). Another skeletal dysplasia that results in severe hypomineralization is hypophosphatasia, which has an autosomal recessive inheritance.
his disorder is notable for a deformed talus and shortened Achilles tendon. he afected foot is abnormally fixed and positioned with equinus (downward pointing), varus (inward rotation), and forefoot adduction. Most cases are considered malformations, with a multifactorial genetic component. However, an association with environmental factors and with early amniocentesis suggests that deformation also plays a role (T redwell, 2001). Sonographically, the footprint is visible in the same plane as the tibia and ibula (Fig. 10-47).