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Autosomal recessive omodysplasia(OMOD1)

MedGen UID:
340513
Concept ID:
C1850318
Disease or Syndrome
Synonyms: Micromelic dysplasia congenita with dislocation of radius; MICROMELIC DYSPLASIA, CONGENITAL, WITH DISLOCATION OF RADIUS; OMOD1; Omodysplasia 1; Omodysplasia generalized form
SNOMED CT: Autosomal recessive omodysplasia (725166005); Micromelic dysplasia, dislocation of radius syndrome (725166005); Omodysplasia 1 (725166005)
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): GPC6 (13q31.3-32.1)
 
Monarch Initiative: MONDO:0009779
OMIM®: 258315
Orphanet: ORPHA93329

Definition

Omodysplasia-1 (OMOD1) is a rare autosomal recessive skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Typical facial features include a prominent forehead, frontal bossing, short nose with a depressed broad bridge, short columella, anteverted nostrils, long philtrum, and small chin. Variable findings are cryptorchidism, hernias, congenital heart defects, and cognitive delay (Elcioglu et al., 2004; Albano et al., 2007). Genetic Heterogeneity of Omodysplasia Also see omodysplasia-2 (OMOD2; 164745), an autosomal dominant form of the disorder in which abnormalities are limited to the upper limbs. The facial changes and typical growth defect of the distal humerus with complex deformity of the elbows appear to be similar in both entities (Baxova et al., 1994). [from OMIM]

Clinical features

From HPO
Hemangioma
MedGen UID:
5477
Concept ID:
C0018916
Neoplastic Process
A hemangioma is a benign tumor characterized by blood-filled spaces lined by benign endothelial cells. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma (in contrast to a hemangioma with small endothelial spaces, which is called capillary hemangioma).
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).
Short humerus
MedGen UID:
316907
Concept ID:
C1832117
Congenital Abnormality
Underdevelopment of the humerus.
Fibular hypoplasia
MedGen UID:
316909
Concept ID:
C1832119
Finding
Underdevelopment of the fibula.
Limited knee flexion
MedGen UID:
326514
Concept ID:
C1839512
Finding
Reduced ability to flex (bend) the knee joint.
Limited knee extension
MedGen UID:
336755
Concept ID:
C1844690
Finding
Reduced ability to extend (straighten) the knee joint.
Short tibia
MedGen UID:
338005
Concept ID:
C1850259
Finding
Underdevelopment (reduced size) of the tibia.
Limited elbow flexion
MedGen UID:
384015
Concept ID:
C1856922
Finding
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Limited elbow flexion/extension
MedGen UID:
368846
Concept ID:
C1968605
Finding
Limited knee flexion/extension
MedGen UID:
368483
Concept ID:
C1968606
Finding
A limited ability of the knee joint to perform extension and flexion.
Hypoplastic distal humeri
MedGen UID:
369808
Concept ID:
C1968607
Finding
Underdevelopment of the distal portion of the humerus.
Anterolateral radial head dislocation
MedGen UID:
369809
Concept ID:
C1968610
Finding
A dislocation of the head of the radius from its socket in the elbow joint in an anterolateral direction.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Pulmonary artery stenosis
MedGen UID:
65965
Concept ID:
C0238397
Anatomical Abnormality
An abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
Disproportionate short-limb short stature
MedGen UID:
342370
Concept ID:
C1849937
Finding
A type of disproportionate short stature characterized by a short limbs but an average-sized trunk.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Limited hip movement
MedGen UID:
343601
Concept ID:
C1851542
Finding
A decreased ability to move the femur at the hip joint associated with a decreased range of motion of the hip.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Increased fibular diameter
MedGen UID:
866750
Concept ID:
C4021100
Finding
Increased width of the cross sectional diameter of the fibula.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Anatomical Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
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).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Narrow palpebral fissure
MedGen UID:
382506
Concept ID:
C2675021
Finding
Reduction in the vertical distance between the upper and lower eyelids.
Axillary pterygium
MedGen UID:
335019
Concept ID:
C1844738
Finding
Presence of a cutaneous membrane (flap) in the armpit.
Popliteal pterygium
MedGen UID:
811750
Concept ID:
C3805420
Finding
A pterygium (or pterygia) occurring in the popliteal region (the back of the knee).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal recessive omodysplasia
Follow this link to review classifications for Autosomal recessive omodysplasia in Orphanet.

Professional guidelines

PubMed

Borochowitz Z, Sabo E, Misselevitch I, Boss JH
Am J Med Genet 1998 Mar 19;76(3):238-44. doi: 10.1002/(sici)1096-8628(19980319)76:3<238::aid-ajmg7>3.0.co;2-m. PMID: 9508243

Recent clinical studies

Etiology

Elçioglu NH, Gustavson KH, Wilkie AO, Yüksel-Apak M, Spranger JW
Pediatr Radiol 2004 Jan;34(1):75-82. Epub 2003 Oct 18 doi: 10.1007/s00247-003-1064-9. PMID: 14566439

Diagnosis

Gordon BL, Champaigne NL, Rogers RC, Frias JL, Leroy JG
Am J Med Genet A 2014 May;164A(5):1234-8. Epub 2014 Jan 23 doi: 10.1002/ajmg.a.36408. PMID: 24458798
Tan TY, McGillivray G, Kornman L, Fink AM, Superti-Furga A, Bonafé L, Francis DI, Savarirayan R
Am J Med Genet A 2005 Jun 15;135(3):324-7. doi: 10.1002/ajmg.a.30754. PMID: 15887278
Borochowitz Z, Sabo E, Misselevitch I, Boss JH
Am J Med Genet 1998 Mar 19;76(3):238-44. doi: 10.1002/(sici)1096-8628(19980319)76:3<238::aid-ajmg7>3.0.co;2-m. PMID: 9508243
al Gazali LI, Abou al-Asaad F
Clin Dysmorphol 1995 Jan;4(1):52-6. PMID: 7735505

Prognosis

Campos-Xavier AB, Martinet D, Bateman J, Belluoccio D, Rowley L, Tan TY, Baxová A, Gustavson KH, Borochowitz ZU, Innes AM, Unger S, Beckmann JS, Mittaz L, Ballhausen D, Superti-Furga A, Savarirayan R, Bonafé L
Am J Hum Genet 2009 Jun;84(6):760-70. Epub 2009 May 28 doi: 10.1016/j.ajhg.2009.05.002. PMID: 19481194Free PMC Article
al Gazali LI, Abou al-Asaad F
Clin Dysmorphol 1995 Jan;4(1):52-6. PMID: 7735505

Clinical prediction guides

Capurro M, Izumikawa T, Suarez P, Shi W, Cydzik M, Kaneiwa T, Gariepy J, Bonafe L, Filmus J
J Cell Biol 2017 Sep 4;216(9):2911-2926. Epub 2017 Jul 10 doi: 10.1083/jcb.201605119. PMID: 28696225Free PMC Article
Gordon BL, Champaigne NL, Rogers RC, Frias JL, Leroy JG
Am J Med Genet A 2014 May;164A(5):1234-8. Epub 2014 Jan 23 doi: 10.1002/ajmg.a.36408. PMID: 24458798
Campos-Xavier AB, Martinet D, Bateman J, Belluoccio D, Rowley L, Tan TY, Baxová A, Gustavson KH, Borochowitz ZU, Innes AM, Unger S, Beckmann JS, Mittaz L, Ballhausen D, Superti-Furga A, Savarirayan R, Bonafé L
Am J Hum Genet 2009 Jun;84(6):760-70. Epub 2009 May 28 doi: 10.1016/j.ajhg.2009.05.002. PMID: 19481194Free PMC Article

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