Crane–Heise syndrome explained

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.^[1]

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^[2]

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.^[2]

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.^[2]

References

1. New syndrome in three affected siblings . . Crane . James . 1981-08-01 . Heise . Robin . 68 . 2 . 235–237 . 10.1542/peds.68.2.235 . 7267231. 8248523 .
2. Crane–Heise syndrome: Two further case reports . European Journal of Medical Genetics . Petit . Florence . Devisme . Louise . 10.1016/j.ejmg.2010.11.004 . 2011. 54 . 2 . 169–172 . 21094705 .