Crane–Heise syndrome

The Crane–Heise syndrome is a very rare and lethal birth defect without a known cause. It was first described in a 1981 publication, and its main signs are facial malformations, lack of bone mineralization, and musculoskeletal anomalies.

Symptoms
According to a 2011 publication that summarizes the nine known cases, the leading symptoms are:
 * restricted intrauterine growth
 * craniofacial malformation
 * lacking mineralization of the calvarium (skull without the lower jaw)
 * cleft lip or palate
 * small jaws (micrognathism)
 * abnormally large distance between the eyes (hypertelorism)
 * malformation of the ears
 * feet malposition
 * absent clavicles
 * genitourinary malformations

Aetiology and differential diagnosis
The clustering of the cases suggests an autosomal recessive disorder (see genetical dominance). In the aminopterin-syndrome sine aminopterin syndrome (ASSAS), a poorly mineralized calvarium is present, too, but many other tell-tale symptoms of Crane–Heise are lacking. A similar disease is cleidocranial dysplasia, but this is an autosomal dominant disease caused by mutations in the RUNX2 gene – and such mutations have not been found in Crane–Heise cases. Chromosomal abnormalities are also absent in the Crane–Heise syndrome.

Diagnosis
As the cause is still unknown, the only diagnostic is ultrasound, which can detect a lack of skull mineralization by the 10th week of pregnancy.