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Distal arthrogryposis type 5D(DA5D)

MedGen UID:
767329
Concept ID:
C3554415
Disease or Syndrome
Synonym: DA5D
SNOMED CT: Distal arthrogryposis type 5D (773396009); Distal arthrogryposis type 5 without ophthalmoparesis (773396009); Distal arthrogryposis type 5 without ophthalmoplegia (773396009); DA5D - distal arthrogryposis type 5D (773396009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ECEL1 (2q37.1)
 
Monarch Initiative: MONDO:0014028
OMIM®: 615065
Orphanet: ORPHA329457

Definition

This autosomal recessive form of distal arthrogryposis, designated DA5D by McMillin et al. (2013), is characterized by severe camptodactyly of the hands, including adducted thumbs and wrists; mild camptodactyly of the toes; clubfoot and/or a calcaneovalgus deformity; extension contractures of the knee; unilateral ptosis or ptosis that is more severe on one side; a round-shaped face; arched eyebrows; a bulbous, upturned nose; and micrognathia. Notably, these patients do not have ophthalmoplegia. For a general phenotypic description and discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). For discussion of genetic heterogeneity of distal arthrogryposis type 5, see DA5 (108145). [from OMIM]

Clinical features

From HPO
Hypoplastic labia majora
MedGen UID:
107566
Concept ID:
C0566899
Finding
Undergrowth of the outer labia.
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).
Thumbs, congenital Clasped
MedGen UID:
98140
Concept ID:
C0431886
Congenital Abnormality
In the resting position, the tip of the thumb is on, or near, the palm, close to the base of the fourth or fifth finger.
Limited knee flexion
MedGen UID:
326514
Concept ID:
C1839512
Finding
Reduced ability to flex (bend) the knee joint.
Limited elbow movement
MedGen UID:
337930
Concept ID:
C1849955
Finding
Calcaneovalgus deformity
MedGen UID:
395489
Concept ID:
C1860450
Anatomical Abnormality
This is a postural deformity in which the foot is positioned up against the tibia. The heel (calcaneus) is positioned downward (that is, the ankle is flexed upward), and the heel is turned outward (valgus).
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Decreased muscle mass
MedGen UID:
373256
Concept ID:
C1837108
Finding
Limited shoulder movement
MedGen UID:
341979
Concept ID:
C1851313
Finding
A limitation of the range of movement of the shoulder joint.
Hypermobility of distal interphalangeal joints
MedGen UID:
338783
Concept ID:
C1851811
Finding
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Furrowed tongue
MedGen UID:
21583
Concept ID:
C0040412
Anatomical Abnormality
Accentuation of the grooves on the dorsal surface of the tongue.
Lagophthalmos
MedGen UID:
57517
Concept ID:
C0152226
Disease or Syndrome
A condition in which the eyelids do not close to cover the eye completely.
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Tongue atrophy
MedGen UID:
66828
Concept ID:
C0241423
Finding
Wasting of the tongue.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
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).

Recent clinical studies

Etiology

Endrakanti M, Sharma J, Ethayathulla AS, Kaur P, Khan SA, Kabra M, Gupta N
Am J Med Genet A 2024 Aug;194(8):e63592. Epub 2024 Apr 3 doi: 10.1002/ajmg.a.63592. PMID: 38568023
Gowda M, Mohan S, Ramesh D, Chinta N
Clin Dysmorphol 2021 Apr 1;30(2):100-103. doi: 10.1097/MCD.0000000000000364. PMID: 33491998
Ullmann U, D'Argenzio L, Mathur S, Whyte T, Quinlivan R, Longman C, Farrugia ME, Manzur A, Willis T, Jungbluth H, Pitt M, Cirak S; UK10K consortium, Feng L, Stewart W, Mein R, Phadke R, Sewry C, Sarkozy A, Muntoni F
Neuromuscul Disord 2018 Sep;28(9):741-749. Epub 2018 Jun 30 doi: 10.1016/j.nmd.2018.05.012. PMID: 30131190
Li X, Zhong B, Han W, Zhao N, Liu W, Sui Y, Wang Y, Lu Y, Wang H, Li J, Jiang M
PLoS One 2015;10(2):e0117158. Epub 2015 Feb 13 doi: 10.1371/journal.pone.0117158. PMID: 25679999Free PMC Article

Diagnosis

Cohen D, Sloma R, Pizem H, Fedida A, Kalfon L, Ovadia R, Segal Z, Kassif Y, Falik Zaccai T
Ophthalmic Genet 2023 Feb;44(1):28-34. Epub 2022 Dec 2 doi: 10.1080/13816810.2022.2141791. PMID: 36459431
Gowda M, Mohan S, Ramesh D, Chinta N
Clin Dysmorphol 2021 Apr 1;30(2):100-103. doi: 10.1097/MCD.0000000000000364. PMID: 33491998
Li X, Zhong B, Han W, Zhao N, Liu W, Sui Y, Wang Y, Lu Y, Wang H, Li J, Jiang M
PLoS One 2015;10(2):e0117158. Epub 2015 Feb 13 doi: 10.1371/journal.pone.0117158. PMID: 25679999Free PMC Article
Patil SJ, Rai GK, Bhat V, Ramesh VA, Nagarajaram HA, Matalia J, Phadke SR
Am J Med Genet A 2014 Nov;164A(11):2857-62. Epub 2014 Aug 5 doi: 10.1002/ajmg.a.36702. PMID: 25099528
Barnett CP, Todd EJ, Ong R, Davis MR, Atkinson V, Allcock R, Laing N, Ravenscroft G
Am J Med Genet A 2014 Jul;164A(7):1846-9. Epub 2014 Apr 29 doi: 10.1002/ajmg.a.36342. PMID: 24782201

Prognosis

Alesi V, Sessini F, Genovese S, Calvieri G, Sallicandro E, Ciocca L, Mingoia M, Novelli A, Moi P
Int J Mol Sci 2021 Feb 20;22(4) doi: 10.3390/ijms22042106. PMID: 33672664Free PMC Article
Ullmann U, D'Argenzio L, Mathur S, Whyte T, Quinlivan R, Longman C, Farrugia ME, Manzur A, Willis T, Jungbluth H, Pitt M, Cirak S; UK10K consortium, Feng L, Stewart W, Mein R, Phadke R, Sewry C, Sarkozy A, Muntoni F
Neuromuscul Disord 2018 Sep;28(9):741-749. Epub 2018 Jun 30 doi: 10.1016/j.nmd.2018.05.012. PMID: 30131190

Clinical prediction guides

Alesi V, Sessini F, Genovese S, Calvieri G, Sallicandro E, Ciocca L, Mingoia M, Novelli A, Moi P
Int J Mol Sci 2021 Feb 20;22(4) doi: 10.3390/ijms22042106. PMID: 33672664Free PMC Article
Ullmann U, D'Argenzio L, Mathur S, Whyte T, Quinlivan R, Longman C, Farrugia ME, Manzur A, Willis T, Jungbluth H, Pitt M, Cirak S; UK10K consortium, Feng L, Stewart W, Mein R, Phadke R, Sewry C, Sarkozy A, Muntoni F
Neuromuscul Disord 2018 Sep;28(9):741-749. Epub 2018 Jun 30 doi: 10.1016/j.nmd.2018.05.012. PMID: 30131190
Hamzeh AR, Nair P, Mohamed M, Saif F, Tawfiq N, Khalifa M, Al-Ali MT, Bastaki F
Med Princ Pract 2017;26(2):195-198. Epub 2017 Jan 18 doi: 10.1159/000456034. PMID: 28114145Free PMC Article

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