Achondroplasia (ACH) / Hypochondroplasia (HCH)

Achondroplasia and Hypochondroplasia

Achondroplasia (ACH; MIM 100800) and hypochondroplasia (HCH; MIM 146000) are autosomal dominant disorders. ACH is caused by specific mutations in FGFR3. ACH represents the most common skeletal dysplasia in humans. It is characterized by rhizomelic dwarfism, trident hands and short fingers, midface hypoplasia with macrocephaly and frontal bossing. A small foramen magnum may cause generalized hypotonia, hyperreflexia or clonus in newborns. HCH is similar to but milder than ACH. Patients are still rhizomelic dwarfs but are not as short, do not have trident hands and the facial manifestations are not as severe. Neurological complications in HCH are not constant findings. HCH is genetically heterogeneous. Not all patients diagnosed clinically with HCH have demonstrable mutations in FGFR3.

Severe achondroplasia with developmental delay and acanthosis nigricans

Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) is an autosomal dominant disorder caused by a specific mutation in FGFR3. These patients have profound short stature, midface hypoplasia, developmental delay, mental retardation and develop acanthosis nigricans. These patients share the FGFR3 mutation also responsible for thanatophoric dysplasia II.

Thanatophoric dysplasia, type I and II

Thanatophoric dysplasia, type I (TD1; MIM 187600) and thanatophoric dysplasia, type II (TD2; MIM 187601) are autosomal dominant disorders caused by mutations in FGFR3. TD is the most common neonatal lethal skeletal dysplasia. Infants are severe rhizomelic dwarfs, have midface hypoplasia and a very small foramen magnum. The ribs are short resulting in a small thorax and respiratory compromise. Types I and II are recognized and correlated with specific FGFR3 mutations. Type I is associated with curved tubular bones and has several different FGFR3 mutations. Type II has a cloverleaf skull and straight femurs and has a specific FGFR3 mutation.