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Arthrogryposis, distal, type 12(DA12)

MedGen UID:
1847896
Concept ID:
C5882704
Disease or Syndrome
Synonym: DA12
 
Gene (location): ADAMTS15 (11q24.3)
 
Monarch Initiative: MONDO:0957819
OMIM®: 620545

Definition

Distal arthrogryposis type 12 (DA12) is characterized by congenital contractures, primarily affecting the small joints of the fingers and toes. Additional features include contractures of the knees and Achilles tendons, spinal stiffness, scoliosis, and orthodontic abnormalities. Radiographic investigations excluded bony abnormalities of the affected joints (Boschann et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hydrocele testis
MedGen UID:
318568
Concept ID:
C1720771
Congenital Abnormality
Accumulation of clear fluid in the between the layers of membrane (tunica vaginalis) surrounding the testis.
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
Ankle flexion contracture
MedGen UID:
332440
Concept ID:
C1837407
Anatomical Abnormality
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Palmar hyperhidrosis
MedGen UID:
346478
Concept ID:
C1856953
Finding
Absent distal interphalangeal creases
MedGen UID:
350011
Concept ID:
C1861349
Finding
Absence of the distal interphalangeal flexion creases of the fingers.
Tapered distal phalanges of finger
MedGen UID:
369964
Concept ID:
C1969237
Finding
A reduction in diameter of the distal phalanx of finger towards the distal end.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Hypoesthesia
MedGen UID:
6974
Concept ID:
C0020580
Finding
Decreased ability to perceive touch.
Acroparesthesia
MedGen UID:
66692
Concept ID:
C0234221
Disease or Syndrome
A type of paresthesia (tingling, pins-and-needles, burning or numbness or stiffness) that occurs in the hands and feet and particularly in the fingers and toes.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Hand muscle atrophy
MedGen UID:
116091
Concept ID:
C0239830
Finding
Muscular atrophy involving the muscles of the hand.
Achilles tendon contracture
MedGen UID:
98052
Concept ID:
C0410264
Anatomical Abnormality
A contracture of the Achilles tendon.
Thoracic kyphosis
MedGen UID:
263148
Concept ID:
C1184919
Finding
Over curvature of the thoracic region, leading to a round back or if sever to a hump.
Congenital finger flexion contractures
MedGen UID:
234659
Concept ID:
C1393871
Congenital Abnormality
Multiple bent (flexed) finger joints that cannot be straightened actively or passively.
Spinal rigidity
MedGen UID:
346721
Concept ID:
C1858025
Finding
Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion.
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Agenesis of maxillary incisor
MedGen UID:
867498
Concept ID:
C4021877
Anatomical Abnormality
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Recent clinical studies

Etiology

Li Y, Nong T, Li Y, Li X, Li Z, Lv H, Xu H, Li J, Zhu M
Mol Genet Genomic Med 2022 Dec;10(12):e2042. Epub 2022 Sep 7 doi: 10.1002/mgg3.2042. PMID: 36069346Free PMC Article
Clippinger BB, Plucknette BF, Soldado F, Turvey BR, Barrera-Ochoa S, Kozin SH, Zlotolow DA
J Hand Surg Am 2022 Feb;47(2):189.e1-189.e9. Epub 2021 Jun 8 doi: 10.1016/j.jhsa.2021.04.009. PMID: 34112543
Dahan-Oliel N, Dieterich K, Rauch F, Bardai G, Blondell TN, Gustafson AG, Hamdy R, Latypova X, Shazand K, Giampietro PF, van Bosse H
Genes (Basel) 2021 Aug 6;12(8) doi: 10.3390/genes12081220. PMID: 34440395Free PMC Article
Gleich SJ, Tien M, Schroeder DR, Hanson AC, Flick R, Nemergut ME
Anesth Analg 2017 Mar;124(3):908-914. doi: 10.1213/ANE.0000000000001822. PMID: 28099287
Li X, Jiang M, Han W, Zhao N, Liu W, Sui Y, Lu Y, Li J
Gene 2013 Sep 25;527(2):630-5. Epub 2013 Jul 11 doi: 10.1016/j.gene.2013.06.082. PMID: 23850728

Diagnosis

Clippinger BB, Plucknette BF, Soldado F, Turvey BR, Barrera-Ochoa S, Kozin SH, Zlotolow DA
J Hand Surg Am 2022 Feb;47(2):189.e1-189.e9. Epub 2021 Jun 8 doi: 10.1016/j.jhsa.2021.04.009. PMID: 34112543
Dahan-Oliel N, Dieterich K, Rauch F, Bardai G, Blondell TN, Gustafson AG, Hamdy R, Latypova X, Shazand K, Giampietro PF, van Bosse H
Genes (Basel) 2021 Aug 6;12(8) doi: 10.3390/genes12081220. PMID: 34440395Free PMC Article
Gleich SJ, Tien M, Schroeder DR, Hanson AC, Flick R, Nemergut ME
Anesth Analg 2017 Mar;124(3):908-914. doi: 10.1213/ANE.0000000000001822. PMID: 28099287
van Paassen BW, van der Kooi AJ, van Spaendonck-Zwarts KY, Verhamme C, Baas F, de Visser M
Orphanet J Rare Dis 2014 Mar 19;9:38. doi: 10.1186/1750-1172-9-38. PMID: 24646194Free PMC Article
Bui TH, Lindholm H, Demir N, Thomassen P
Prenat Diagn 1992 Dec;12(12):1047-53. doi: 10.1002/pd.1970121211. PMID: 1287640

Therapy

Gleich SJ, Tien M, Schroeder DR, Hanson AC, Flick R, Nemergut ME
Anesth Analg 2017 Mar;124(3):908-914. doi: 10.1213/ANE.0000000000001822. PMID: 28099287
Greggi T, Lolli F, Di Silvestre M, Martikos K, Vommaro F, Maredi E, Giacomini S, Baioni A, Cioni A
Stud Health Technol Inform 2012;176:334-7. PMID: 22744523

Prognosis

McAdow J, Yang S, Ou T, Huang G, Dobbs MB, Gurnett CA, Greenberg MJ, Johnson AN
JCI Insight 2022 Jun 22;7(12) doi: 10.1172/jci.insight.152466. PMID: 35579956Free PMC Article
van Paassen BW, van der Kooi AJ, van Spaendonck-Zwarts KY, Verhamme C, Baas F, de Visser M
Orphanet J Rare Dis 2014 Mar 19;9:38. doi: 10.1186/1750-1172-9-38. PMID: 24646194Free PMC Article
Li X, Jiang M, Han W, Zhao N, Liu W, Sui Y, Lu Y, Li J
Gene 2013 Sep 25;527(2):630-5. Epub 2013 Jul 11 doi: 10.1016/j.gene.2013.06.082. PMID: 23850728
Shyy W, Wang K, Sheffield VC, Morcuende JA
J Pediatr Orthop 2010 Apr-May;30(3):231-4. doi: 10.1097/BPO.0b013e3181d35e3f. PMID: 20357587Free PMC Article

Clinical prediction guides

McAdow J, Yang S, Ou T, Huang G, Dobbs MB, Gurnett CA, Greenberg MJ, Johnson AN
JCI Insight 2022 Jun 22;7(12) doi: 10.1172/jci.insight.152466. PMID: 35579956Free PMC Article
Echaniz-Laguna A, Dubourg O, Carlier P, Carlier RY, Sabouraud P, Péréon Y, Chapon F, Thauvin-Robinet C, Laforêt P, Eymard B, Latour P, Stojkovic T
Neurology 2014 May 27;82(21):1919-26. Epub 2014 Apr 30 doi: 10.1212/WNL.0000000000000450. PMID: 24789864
Li X, Jiang M, Han W, Zhao N, Liu W, Sui Y, Lu Y, Li J
Gene 2013 Sep 25;527(2):630-5. Epub 2013 Jul 11 doi: 10.1016/j.gene.2013.06.082. PMID: 23850728
Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A
Proc Natl Acad Sci U S A 2013 Mar 19;110(12):4667-72. Epub 2013 Mar 4 doi: 10.1073/pnas.1221400110. PMID: 23487782Free PMC Article
Shyy W, Wang K, Sheffield VC, Morcuende JA
J Pediatr Orthop 2010 Apr-May;30(3):231-4. doi: 10.1097/BPO.0b013e3181d35e3f. PMID: 20357587Free PMC Article

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