Digitotalar dysmorphism

MedGen UID:: 987924
•Concept ID:: CN305314
•: Disease or Syndrome

Synonym:	Distal arthrogryposis type 1
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Monarch Initiative:	MONDO:0015240
Orphanet:	ORPHA1146

Definition

In general, the distal arthrogryposes are a group of disorders characterized by contractures mainly involving the distal parts of the limbs. The hands have a characteristic position with medially overlapping fingers, clenched fists, ulnar deviation of fingers, and camptodactyly, and the feet have deformities. Contractures at other joints are variable; there are no associated visceral anomalies, and intelligence is normal. Bamshad et al. (1996) revised the classification by Hall et al. (1982) of the common mendelian arthrogryposis syndromes. The various phenotypic forms of distal arthrogryposis are classified hierarchically according to the proportion of features they share with one another and are designated DA1 through DA10 (summary by Bamshad et al., 2009). The prototypic distal arthrogryposis is type 1 (DA1), which is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected. While the pattern of affected joints is consistent, the degree to which the joints are affected is highly variable, with equinovarus deformities ranging from mild to severe and hand involvement ranging from isolated hypoplasia of the distal interphalangeal crease of the fifth digit to severely clenched fists and ulnar deviation of the wrist (summary by Bamshad et al., 1996). Classically, DA was defined as being without overt neurologic or muscle disease (Lin et al., 1977 and Hall et al., 1982), although more recent evidence suggests that DA1A results from muscle dysfunction (Robinson et al., 2007; Mokbel et al., 2013; Davidson et al., 2013) (summary by Bamshad et al., 2009). The congenital contractures in distal arthrogryposis type 2B (Sheldon-Hall syndrome; see 601680) are similar to those observed in DA1, but affected individuals tend to have more prominent nasolabial folds, downslanting palpebral fissures, and a small mouth. DA2B is thought to be the most common of the distal arthrogryposis disorders (summary by Bamshad et al., 2009). A review of patients diagnosed with DA1 or DA2B by Beck et al. (2013) found that the same mutation caused DA1 in some families and DA2B in others. There were no significant differences among the clinical characteristics of DA by locus or between each locus and DA1 or DA2B. The authors suggested that DA1 and DA2B might represent phenotypic extremes of the same disorder. Genetic Heterogeneity of Distal Arthrogryposes Other forms of distal arthrogryposis include DA1B (614335), caused by mutation in the MYBPC1 gene (160794) on chromosome 12q23; DA1C (619110), caused by mutation in the MYLPF gene (617378) on chromosome 16p11; DA2A (Freeman-Sheldon syndrome, 193700), caused by mutation in the MYH3 gene (160720) on chromosome 17p13; DA2B1 (601680), caused by mutation in the TNNI2 gene (191043) on 11p15; DA2B2 (618435), caused by mutation in the TNNT3 gene (600692) on chromosome 11p15; DA2B3 (618436), caused by mutation in the MYH3 gene (160720) on chromosome 17p13; DA3 (Gordon syndrome, 114300) and DA5 (108145), caused by mutation in the PIEZO2 gene (613629) on chromosome 18p11; DA4 (609128), which has not been mapped; DA5D (615065), caused by mutation in the ECEL1 gene (605896) on chromosome 2q36; DA6 (108200); DA7 (158300), caused by mutation in the MYH8 gene (160741) on chromosome 17p13.1; DA9 (121050), caused by mutation in the FBN2 gene (612570) on chromosome 5q23; DA10 (187370), which maps to chromosome 2q; DA11 (620019), caused by mutation in the MET gene (164860) on chromosome 7q31; and DA12 (620545), caused by mutation in the ADAMTS15 gene (607509) on chromosome 11q25. Distal arthrogryposis-8 (DA8) has been reclassified as contractures, pterygia, and variable skeletal fusions syndrome-1A (CPSKF1A; 178110). See 277720 for discussion of a possible autosomal recessive form of DA2A. See 208155 for a description of Illum syndrome, which includes 'whistling face,' central nervous system dysfunction, and calcium deposition in central nervous system and muscle. There are other forms of arthrogryposis multiplex congenita (AMC), including a lethal congenital form (see LCCS1, 253310). [from OMIM]