Summary
Distal arthrogryposis type 7 (DA7), often referred to as trismus-pseudocamptodactyly syndrome or Hecht syndrome, is caused by mutation in the MYH8 gene. Heredity is autosomal dominant. Large multigenerational families with several affected members have been reported.
Detailed clinical description
Expressivity is highly variable, although penetrance tends to be complete. Inability to open the mouth completely (trismus), short finger-flexor tendons such that dorsiflexion of the wrist resulted in camptodactyly, pseudocamptodactyly, soft tissue syndactyly of the toes, short leg muscles resulting in foot deformity (shortness of the Achilles tendon, hammertoe, talipes equinovarus, and metatarsus varus), hip problems such as congenital dysplasia, muscle cramps, micrognathia, and abnormal swallowing demonstrated by manometry can be observed in different combinations.
The trismus is thought to result from bilateral hyperplasia of the mandibular coronoid processes. The trismus may limit nutrition to liquids, compromise oral hygiene, and give aspiration. Open bilateral coronoidectomy can be a successful and durable management option for trismus in patients with DA7. In some cases trismus may completely relapse after few years after surgery (and a second surgery can be done to address the problem again).
In large families measuring mouth opening and wrist angles can be sufficient to divide family members into affected and unaffected. Although affected individuals may show normal height, their height can be lower than that of unaffected sibs of the same sex in the family. Mild facial dysmorphism can be seen and includes macrocephaly, facial asymmetry, ptosis and downslanting palpebral features, deep philtrum, and a long chin.
Molecular genetics
The first MYH8 mutation identified to be cause of DA7 is R674Q (p.Arg674Gln). The possibility of germline mosacism for this mutation has been documented.
Genetic testing strategy
Targeted mutation analysis can be done to detect the known disease-causing mutations in MYH8. However, since arthrogryposes are genetically and clinically heterogeneous, full MYH8 gene sequencing (EXOME GENE) or panel testing (EXOME PANEL) is recommended.
Panel testing recommended at Breda Genetics for this condition:
