Details
23 week gestational female fetus.
The main image is a radiograph (see related content); this image shows a full-body frontal view.
Thanataphoric Dysplasia (TD) type II is a rare autosomal dominant inherited skeletal dysplasia affecting the gene FGFR3. A single nucleotide polymorphism results in an FGFR3 receptor that is locked in a metastable ligand-independent active form, causing hyperactivity of the cytoplasmic tyrosine-kinase domain. This has a pro-apoptotic effect on chondrocytes, resulting in premature ossification and hypoplasia of the fetal cartilaginous skeleton, and a pro-mitotic effect on neurons, resulting in macrencephaly and other brain abnormalities.
The disease is characterized by pronounced micromelemia and a narrow thoracic cage with normal trunk length and macrencephaly. Type II is differentiated by the presence of cloverleaf skull (due to craniosynostosis), more severe brain abnormality, and straight tubular bones.
In this case, there is severe megacephaly and megalencephaly, along with severe cranyosynostosis, manifested as cloverleaf skull. Note the bulging forehead with marked frontal bossing in gross images. The brain displays characteristic malformations of thanatophoric dwarfism, with prominent radially directed folds in both the inferior and medial temporal lobes. The vertebral bodies are rounded and display severe platyspondyly, with abnormally straight pedicles, a notable feature of FGFR3 pathologies. The long bones are short, straight, and thick, with flared and cupped metaphyses. Note the straight “ice cream cone” femurs with lateral metaphyseal spurs, a distinguishing feature of TD type II. Both the hands and feet are malformed. The metatarsals are short and curved, and the phalanges are short and bullet shaped, another feature of FGFR3 mutations. The ribs are quite short with pronounced posterior scalloping and wide, cupped costochondral junctions. The ribcage itself is strikingly narrow; note the distended abdomen in gross images. The pelvic bones display hypoplastic iliac wings with malformation and non-ossification of the pubic bones, and characteristic triple-pronged acetabula.
