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Gordon syndrome(DA3)

MedGen UID:
66314
Concept ID:
C0220666
Disease or Syndrome
Synonyms: Arthrogryposis distal type 3; Arthrogryposis multiplex congenita distal type 2a; ARTHROGRYPOSIS MULTIPLEX CONGENITA, DISTAL, TYPE IIA; Camptodactyly, cleft palate, and clubfoot; DA3; Gordon's syndrome
SNOMED CT: Distal arthrogryposis type 3 (897570002); Camptodactyly, cleft palate, clubfoot syndrome (897570002); Distal arthrogryposis type IIA (897570002); Gordon syndrome (897570002)
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.
 
Gene (location): PIEZO2 (18p11.22-11.21)
 
Monarch Initiative: MONDO:0007252
OMIM®: 114300
Orphanet: ORPHA376

Definition

DA3, or Gordon syndrome, is distinguished from other distal arthrogryposes by short stature and cleft palate (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA3 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 5 (DA5; 108145) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of ocular abnormalities and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders may represent variable expressivity of the same condition. For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (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).
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.
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
Cutaneous finger syndactyly
MedGen UID:
866898
Concept ID:
C4021254
Congenital Abnormality
A soft tissue continuity in the A/P axis between two fingers that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two fingers that lies significantly distal to the flexion crease that overlies the metacarpophalangeal joint of the adjacent fingers.
Ulnar deviation of the hand or of fingers of the hand
MedGen UID:
892857
Concept ID:
C4048199
Finding
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).
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Chiari type I malformation
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line)
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
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.
Distal arthrogryposis
MedGen UID:
120512
Concept ID:
C0265213
Disease or Syndrome
An inherited primary limb malformation disorder characterized by congenital contractures of two or more different body areas and without primary neurologic and/or muscle disease that affects limb function.
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Thoracolumbar scoliosis
MedGen UID:
196671
Concept ID:
C0749379
Anatomical Abnormality
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Decreased hip abduction
MedGen UID:
332244
Concept ID:
C1836589
Finding
Reduced ability to move the femur outward to the side.
Decreased muscle mass
MedGen UID:
373256
Concept ID:
C1837108
Finding
Down-sloping shoulders
MedGen UID:
346461
Concept ID:
C1856872
Finding
Low set, steeply sloping shoulders.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Camptodactyly of toe
MedGen UID:
867404
Concept ID:
C4021774
Anatomical Abnormality
Camptodactyly is a painless flexion contracture of the proximal interphalangeal (PIP) joint that is usually gradually progressive. This term refers to camptodactyly of one or more toes.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
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).
Submucous cleft hard palate
MedGen UID:
98472
Concept ID:
C0432103
Congenital Abnormality
Hard-palate submucous clefts are characterized by bony defects in the midline of the bony palate that are covered by the mucous membrane of the roof of the mouth. It may be possible to detect a submucous cleft hard palate upon palpation as a notch in the bony palate.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
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).
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
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).
Ophthalmoplegia
MedGen UID:
45205
Concept ID:
C0029089
Sign or Symptom
Paralysis of one or more extraocular muscles that are responsible for eye movements.

Professional guidelines

PubMed

Glover M, O'shaughnessy KM
Curr Opin Nephrol Hypertens 2011 Jan;20(1):16-22. doi: 10.1097/MNH.0b013e32834132bc. PMID: 21088576

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Etiology

Singh V, Van Why SK
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Horm Metab Res 2012 Nov;44(12):867-78. Epub 2012 Aug 29 doi: 10.1055/s-0032-1321851. PMID: 22932914
Puura A, Schultz R
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Diagnosis

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Med Clin North Am 2024 Jan;108(1):157-172. Epub 2023 Jul 27 doi: 10.1016/j.mcna.2023.06.005. PMID: 37951648
Peces R, Peces C, Espinosa L, Mena R, Blanco C, Tenorio-Castaño J, Lapunzina P, Nevado J
Genes (Basel) 2023 Sep 27;14(10) doi: 10.3390/genes14101878. PMID: 37895227Free PMC Article
Sharma P, Chatrathi HE
Cell Commun Signal 2023 Oct 16;21(1):286. doi: 10.1186/s12964-023-01269-z. PMID: 37845702Free PMC Article
Athimulam S, Lazik N, Bancos I
Endocrinol Metab Clin North Am 2019 Dec;48(4):701-715. Epub 2019 Sep 25 doi: 10.1016/j.ecl.2019.08.003. PMID: 31655771
O'Shaughnessy KM
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Pediatr Nephrol 2020 Mar;35(3):405-407. Epub 2019 Sep 16 doi: 10.1007/s00467-019-04352-1. PMID: 31529157
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Endocrinol Metab Clin North Am 2019 Dec;48(4):701-715. Epub 2019 Sep 25 doi: 10.1016/j.ecl.2019.08.003. PMID: 31655771
Glover M, O'Shaughnessy KM
Clin Exp Pharmacol Physiol 2013 Dec;40(12):876-84. doi: 10.1111/1440-1681.12115. PMID: 23683032
Stowasser M, Pimenta E, Gordon RD
Endocrinol Metab Clin North Am 2011 Jun;40(2):343-68, viii. doi: 10.1016/j.ecl.2011.01.007. PMID: 21565671
Puura A, Schultz R
J Inherit Metab Dis 2005;28(6):1157-8. doi: 10.1007/s10545-005-0165-z. PMID: 16435216

Prognosis

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Park JS, Park E, Hyun HS, Ahn YH, Kang HG, Ha IS, Cheong HI
J Pediatr Endocrinol Metab 2017 Mar 1;30(3):361-364. doi: 10.1515/jpem-2016-0309. PMID: 28222034
Vehaskari VM
Curr Opin Pediatr 2004 Apr;16(2):182-7. doi: 10.1097/00008480-200404000-00012. PMID: 15021199
al-Ghamdi MA, Polomeno RC, Chitayat D, Azouz EM, Teebi AS
Am J Med Genet 1997 Sep 5;71(4):401-5. doi: 10.1002/(sici)1096-8628(19970905)71:4<401::aid-ajmg6>3.0.co;2-w. PMID: 9286445
Gericke GS, Hall JG, Nelson MM, Beighton PH
Clin Genet 1984 Feb;25(2):155-62. PMID: 6538466

Clinical prediction guides

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Saudi J Kidney Dis Transpl 2020 Sep-Oct;31(5):1134-1139. doi: 10.4103/1319-2442.301183. PMID: 33229781
Tsuji S, Yamashita M, Unishi G, Takewa R, Kimata T, Isobe K, Chiga M, Uchida S, Kaneko K
BMC Nephrol 2013 Jul 31;14:166. doi: 10.1186/1471-2369-14-166. PMID: 23902721Free PMC Article
Vehaskari VM
Curr Opin Pediatr 2004 Apr;16(2):182-7. doi: 10.1097/00008480-200404000-00012. PMID: 15021199

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