Arthrogryposis refers to multiple congenital joint contractures and resulting restriction of movements. It is a clinical feature that occurs as part of >300 different disorders. Distal arthrogryposes are a specific type of arthrogryposis disorders that involve contractures in ≥2 distal parts of the limbs and the absence of neurological/muscle disease. Pathogenic variants in >10 genes (TPM2, MYBPC1, MYH3, TNNT3, TNNI2, MYH8, FBN2, PIEZO2, ECEL1, DOK7, RAPSN) that encode proteins important for the myofibers contractile functions, can cause distal arthrogryposis. 1, 2
Major clinical symptoms for arthrogryposis include the following 1, 2:
- Upper limbs:
- camptodactyly (permanent banding of one or more fingers)
- hypoplastic and/or absent flexion creases
- overriding fingers
- ulnar deviation at the wrist
- Lower limbs:
- talipes equinovarus (clubfoot)
- vertical talus (rocker bottom feet)
- other foot deformities (calcaneovalgus talipes, metatarsus varus)
- ≥2 above major symptoms in an individual
- ≥1 of the major symptoms in an individual with an affected family member (with ≥2 symptoms)
- Known pathogenic variant in one of the following genes: TPM2, MYBPC1, MYH3, TNNT3, TNNI2, MYH8, FBN2, PIEZO2, ECEL1, DOK7, RAPSN
There is no cure for arthrogryposis but different management and interventions can relieve symptoms 1, 2
- Surgical correction of the contractures
- Complex multi-disciplinary treatment involving pediatricians, physiotherapists, geneticists, orthopedic surgeons, and orthotic specialists.
- Holt-Oram syndrome
- Tuberous sclerosis
- Otopalatodigital syndrome
- Nemaline myopathy
- Oculodentodigital syndrome
- Ophthalmomandibulomelic dysplasia
To confirm/establish the diagnosis, CENTOGENE offers the following tests:
- Arthrogryposis NGS Panel which includes sequencing of the genes TPM2, MYBPC1, MYH3, TNNT3, TNNI2, MYH8, FBN2, PIEZO2, ECEL1, DOK7, RAPSN
- Arthrogryposis NGS Panel + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data
- Individuals with a positive family history of distal arthrogryposis.
- Individuals that meet the diagnostic criteria for distal arthrogryposis (regardless of family history).
Why is this test good for the patient?
Confirmation of a clinical diagnosis through genetic testing of Arthrogryposis can allow for genetic counseling and may direct medical management.