Table 3.

Disorders to Consider in the Differential Diagnosis of Autosomal Dominant Multiple Epiphyseal Dysplasia (MED)

DisorderGeneMOICharacteristic Radiographic FeaturesOverlapping Clinical FeaturesComments
Multiple epiphyseal dysplasia, recessive (EDM4/rMED) SLC26A2 ARDouble-layered patella (i.e., presence of a separate anterior & posterior ossification layer) observed on lateral knee radiographs in ~60% (Finding appears to be age related & may not be apparent in adults.)
  • Joint pain (usually in hips &/or knees); malformations of hands, feet, & knees; scoliosis
  • Onset of articular pain variable, but usually in late childhood
  • Stature usually w/in normal range prior to puberty; in adulthood, stature only slightly diminished (range: 150-180 cm)
  • Mild functional disability
~50% have an abnormal finding at birth, incl clubfoot, clinodactyly, or (rarely) cystic ear swelling.
Legg-Calve-Perthes (LCPD)
(OMIM 150600)		 COL2A1 ADRadiographic changes observed in LCPD differ from those of MED, w/more involvement of metaphyses & femoral neck.Hip pain
  • Juvenile osteonecrosis of the femoral head caused by disruption of blood supply during endochondral ossification
  • Usually affects males ages 3-15 yrs
  • Up to 20% have bilateral involvement.
  • Several studies have identified differences between bilateral & unilateral LCPD (Of note, bilateral LCPD is more severe).
Mild spondyloepiphyseal dysplasia congenita (SEDc)
(OMIM 183900)		 COL2A1 ADCOL2A1 missense variants identified in 2 persons w/mild SEDc & phenotypic features consistent w/MED based on limited clinical data & radiographic images 2
Beukes familial hip dysplasia (BFHD) 3
(OMIM 142669)		 UFSP2 ADShares many clinical & radiographic features w/MED & is now recognized as a form of MED 3First identified in 47 persons in 6 generations of an Afrikaner family in South Africa 4
Pseudoachondroplasia COMP ADSee Genetically Related Disorders.See Genetically Related Disorders.
1.

Some forms of LCPD have been shown to result from a recurrent p.Gly1170Ser variant in exon 50 of COL2A1 [Liu et al 2005] while other COL2A1 pathogenic variants, such as p.Gly393Ser [Kannu et al 2011] and p.Gly717Ser [Miyamoto et al 2007], have also been associated with LCPD and avascular necrosis of the femoral head.

2.
3.

The International Nosology and Classification of Genetic Skeletal Disorders – 2015 Revision recognized BFHD as a form of MED [Bonafe et al 2015].

4.

From: Multiple Epiphyseal Dysplasia, Autosomal Dominant

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