Arthrogryposis, distal, type 2B (DA2B)

newborn-white-capSummary

DA2B is thought to be the most common of the distal arthrogryposis disorders. Distal arthrogryposis is a clinically and genetically heterogeneous disorder characterized by clenched fist, overlapping fingers, camptodactyly, ulnar deviation, and positional foot deformities from birth. If distal arthrogryposis type 1 (DA1) is not associated with other abnormalities, other forms of DA such as DA type2 have additional phenotypic features. DA2A is called Freeman-Sheldon syndrome (FSS), whereas DA2B is called Sheldon-Hall syndrome (SHS). Contractures in DA2B are similar to those observed in DA1, but affected individuals tend to have more prominent nasolabial folds, downslanting palpebral fissures, and a small mouth (small mouth is also distinctive of DA2A – whistling face syndrome).

Detailed clinical description

Sometimes features intermediate between DA1 and DA2A can be seen. All clinical signs so far observed include: multiple joint contractures with tight hips and dislocated right knee,  bilateral ulnar wrist deviation and flexion contracture of the metacarpophalangeal joints, bilateral adduction contracture of the thumbs, triangular face, downslanting/narrow palpebral fissures, attached earlobes, posteriorly angulated ears, prominent nasolabial folds, small mouth, small mandible, facial asymmetry, hypertelorism, high nasal bridge, malar hypoplasia, micrognathia, arched palate,  hearing impairment, notched chin, smooth palms, ptosis, webbed neck, scoliosis/kyphoscoliosis, short stature to normal height, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus.

Although the small mouth is typical of both DA2A and DA2B, the shape of the mouth and chin can be different in DA2B and feeding difficulties at birth or the need surgical revision may be absent. Mildly increased serum creatine kinase without clinical muscle weakness has been documented. However, muscle weakness can be seen. Facial involvement may be mild or absent in some cases.

Molecular genetics

DA2B is genetically heterogeneous. Mutations have been so far detected in the MYH3, TNNT3, TNNI2 and TPM2 genes. The transmission is autosomal dominant. Mostly missense heterozygous mutations have been reported to cause DA2B: TNNI2 gene: c.521G>A (p.Arg174Gln), c.527_529delAGA (p.Lys176del), c.466C>T (p.Arg156Ter), c.499_501delGAG (p.Glu167del); MYH3 gene: c.700G>A (p.Ala234Thr), c.1385A>G (p.Asp462Gly), c.1123G>A (p.Glu375Lys), c.2590delCTC, c.533C>T (p.Thr178Ile); TPM2 gene: c.397C>T (p.Arg133Trp); TNNT3 gene: c.188G>A (p.Arg63His). In a patient with clinically diagnosed DA2B no mutation in the aforementioned genes was identified. A heterozygous de novo 7 Mb deletion of 8q21.11-8q21.13 containing 23 genes was found instead (the authors identified three favoured candidate genes – HEY1, FABP5 and FABP4 – as potential causes of the phenotype).

Genetic testing strategy

Targeted mutation analysis can be done to detect known disease-causing mutations in in the MYH3, TNNT3, TNNI2 or TPM2 gene. However, since arthrogryposes are clinically heterogeneous and consistent clinical overlap can be seen among different subtypes, panel testing (EXOME PANEL) is recommended.

Panel testing recommended at Breda Genetics for this condition:

[siteorigin_widget class=”SiteOrigin_Widget_Button_Widget”][/siteorigin_widget]
[siteorigin_widget class=”SiteOrigin_Widget_Button_Widget”][/siteorigin_widget]

References: 

OMIM: 601680

DA2B,

PMID 21722758.

Search here for the panel

Or try our Exome and Genome sequencing

Tag

Leave a Reply

Your email address will not be published. Required fields are marked *

Feel free to call us to book your appointment

CONTACT FORM

CONTACT FORM

Enter Email
Confirm Email
Invio

Subscribe to our newsletter to receive news on the world of genetics.

We regularly send specific information for Patients and Professionals with updates and news.
No Spam, that's information.

Newsletter Signup

Newsletter Signup

First
Last