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Multiple epiphyseal dysplasia type 4(EDM4)

MedGen UID:
376164
Concept ID:
C1847593
Disease or Syndrome
Synonyms: EDM4; Multiple epiphyseal dysplasia with bilayered patellae; Multiple epiphyseal dysplasia with clubfoot; Multiple epiphyseal dysplasia with double-layered patella; Multiple epiphyseal dysplasia, autosomal recessive; Multiple Epiphyseal Dysplasia, Recessive
SNOMED CT: Multiple epiphyseal dysplasia type 4 (715672007); Autosomal recessive multiple epiphyseal dysplasia (715672007)
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): SLC26A2 (5q32)
 
Monarch Initiative: MONDO:0009189
OMIM®: 226900
Orphanet: ORPHA93307

Disease characteristics

Excerpted from the GeneReview: SLC26A2-Related Multiple Epiphyseal Dysplasia
SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, including clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild. [from GeneReviews]
Authors:
Sheila Unger  |  Andrea Superti-Furga   view full author information

Additional description

From MedlinePlus Genetics
Multiple epiphyseal dysplasia is a disorder of cartilage and bone development primarily affecting the ends of the long bones in the arms and legs (epiphyses). There are two types of multiple epiphyseal dysplasia, which can be distinguished by their pattern of inheritance. Both the dominant and recessive types have relatively mild signs and symptoms, including joint pain that most commonly affects the hips and knees, early-onset arthritis, and a waddling walk. Although some people with multiple epiphyseal dysplasia have mild short stature as adults, most are of normal height. The majority of individuals are diagnosed during childhood; however, some mild cases may not be diagnosed until adulthood.

Recessive multiple epiphyseal dysplasia is distinguished from the dominant type by malformations of the hands, feet, and knees and abnormal curvature of the spine (scoliosis). About 50 percent of individuals with recessive multiple epiphyseal dysplasia are born with at least one abnormal feature, including an inward- and upward-turning foot (clubfoot), an opening in the roof of the mouth (cleft palate), an unusual curving of the fingers or toes (clinodactyly), or ear swelling. An abnormality of the kneecap called a double-layered patella is also relatively common.  https://medlineplus.gov/genetics/condition/multiple-epiphyseal-dysplasia

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
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).
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Limited elbow flexion
MedGen UID:
384015
Concept ID:
C1856922
Finding
Double-layered patella
MedGen UID:
346472
Concept ID:
C1856923
Congenital Abnormality
An anomaly of the patella characterized by two layers visible on lateral knee X-ray such that one layer is in front of the other in the sagittal orientation (See Figure 2A and 3B of PMID:12966518). This finding persists into adulthood.
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).
Multiple epiphyseal dysplasia
MedGen UID:
6461
Concept ID:
C0026760
Congenital Abnormality
A rare group of primary bone dysplasia disorders characterized by the association of epiphyseal anomalies of long bones causing joint pain early in life, recurrent osteochondritis and early arthrosis. This group contains an heterogeneous group of diseases with variable expression. Common reported clinical signs include waddling gait and pain at onset, and moderate short stature. Some forms are mainly limited to the femoral epiphyses, while several other syndromes are characterized by the association of multiple epiphyseal dysplasia with other clinical manifestations such as myopia, deafness and facial dysmorphism. Diagnosis relies on identification of the radiological features.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Epiphyseal dysplasia
MedGen UID:
95932
Concept ID:
C0392476
Congenital Abnormality
Flat capital femoral epiphysis
MedGen UID:
334001
Concept ID:
C1842155
Finding
An abnormal flattening of the proximal epiphysis of the femur.
Hypoplasia of the femoral head
MedGen UID:
384014
Concept ID:
C1856920
Anatomical Abnormality
Underdevelopment of the femoral head.
Developmental dysplasia of the hip
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21. DDH3 (620690) is caused by mutation in the LRP1 gene (107770) on chromosome 12q13.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Multiple epiphyseal dysplasia type 4 in Orphanet.

Professional guidelines

PubMed

Liu W, Cao J, Shi X, Li Y, Qiao F, Wu Y
Orphanet J Rare Dis 2023 Oct 25;18(1):336. doi: 10.1186/s13023-023-02955-4. PMID: 37875969Free PMC Article
Sawamoto K, Álvarez González JV, Piechnik M, Otero FJ, Couce ML, Suzuki Y, Tomatsu S
Int J Mol Sci 2020 Feb 23;21(4) doi: 10.3390/ijms21041517. PMID: 32102177Free PMC Article
Nitschke Y, Rutsch F
Curr Osteoporos Rep 2017 Aug;15(4):255-270. doi: 10.1007/s11914-017-0370-3. PMID: 28585220

Recent clinical studies

Etiology

Markova T, Kenis V, Melchenko E, Alieva A, Nagornova T, Orlova A, Ogorodova N, Shchagina O, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Aug 24;13(9) doi: 10.3390/genes13091512. PMID: 36140680Free PMC Article

Diagnosis

Markova T, Kenis V, Melchenko E, Alieva A, Nagornova T, Orlova A, Ogorodova N, Shchagina O, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Aug 24;13(9) doi: 10.3390/genes13091512. PMID: 36140680Free PMC Article

Clinical prediction guides

Markova T, Kenis V, Melchenko E, Alieva A, Nagornova T, Orlova A, Ogorodova N, Shchagina O, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Aug 24;13(9) doi: 10.3390/genes13091512. PMID: 36140680Free PMC Article

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