Thanatophoric dysplasia

A form of short-limbed (micromelic) dwarfism that usually causes death within the first few hours after birth. Thanatophoric dysplasia is due to a lethal mutation (change) in the same gene that produces achondroplasia, a familiar and far more common form of short-limbed dwarfism that is compatible with life.

In thanatophoric dysplasia the bones of the arms and legs are very short. The ribs are also extremely short. The vertebral bodies of the spine are greatly reduced in height with wide spaces between them. The rib cage is small, leading to respiratory insufficiency and often to death.

Thanatophoric dysplasia (TD) is divided into two types, depending primarily upon whether the bone in the upper leg (the femur) is curved or straight. Babies with a curved short femur have type I thanatophoric dysplasia (TD1). This is the more common kind of TD.

Babies with a straight, somewhat longer femur have type II thanatophoric dysplasia (TD2). All babies with TD2 also have a severe malformation of the skull, brain and face called cloverleaf skull (or kleeblattschadel) in which the skull from the front looks like a three-leafed clover.

All babies with severe cloverleaf skull appear to have TD2. This malformation can be detected before birth by ultrasound.

Patients with TD1 have mutations in a gene that codes for fibroblast growth factor receptor-3 (FGFR3) which is also mutant in a much more familiar form of dwarfism, achondroplasia. Patients with TD2 have a different mutation in FGFR3.

Thanatophoric dysplasia, also called thanatophoric dwarfism, was discovered in 1967 by Pierre Maroteaux and his coworkers who used the Greek term “thanatophoric” meaning death-bringing.