Table 2. [Forms of Spondyloepiphyseal Dysplasia of...]. - GeneReviews®

Gene(s)	Disorder	MOI	Clinical Features of Differential Diagnosis Disorder	Distinguishing Features/ Comment
CCN6 (WISP3)	Progressive pseudorheumatoid dysplasia (PED)	AR	Predominant involvement of articular cartilage w/progressive joint stiffness & enlargement & w/o inflammation. Onset (age ~3-6 yrs) begins w/involvement of interphalangeal joints; later involvement of large joints & spine causes significant joint contractures, gait disturbance, & scoliosis &/or kyphosis, → abnormal posture & significant morbidity. Short stature (<3rd centile) becomes evident in adolescence.	Unlike X-linked SEDT, joint swelling & hand involvement are common features of PED.
COL2A1	SED congenita (SEDC) (See Type II Collagen Disorders Overview.)	AD ¹	Usually evident at birth w/disproportionate short stature, short extremities, broad chest, characteristic facies, myopia, & ↑ incidence of cleft palate & hearing loss. Delayed/poor ossification of vertebrae & pubic bones; long bones are short w/hypoplastic epiphyses. ↑ risk for tracheolaryngomalacia & related respiratory complications & retinal detachment. ↑ risk for cervical instability.	SED congenita is most common form of SED.
Spondyloperipheral dysplasia (See Type II Collagen Disorders Overview.)	AD	Mild-to-moderate disproportionate short stature & short extremities, brachydactyly type E, short ulnae, variable clubfeet, cleft palate, myopia, & hearing loss; ovoid vertebra, delayed ossification of pubic bones, & flattened & irregular epiphyses in long bones. Premature hip arthrosis causes joint pain.
COL2A1 COL9A1 COL9A2 COL9A3 COL11A1 COL11A2	Stickler syndrome	AD AR ²	Connective tissue disorder; can incl high myopia, hearing loss (both conductive & sensorineural); midfacial underdevelopment & cleft palate (either alone or as part of Pierre Robin sequence); & mild SED &/or precocious arthritis.
COL9A1 COL9A2 COL9A3 COMP MATN3	Multiple epiphyseal dysplasia, autosomal dominant (MED)	AD	Presents early in childhood, usually w/pain in hips &/or knees after exercise; affected children complain of fatigue w/long-distance walking; waddling gait may be present. Adult height in lower range of normal or mildly shortened; limbs relatively short compared to trunk; progressive pain & joint deformity → early-onset osteoarthritis esp of large weight-bearing joints.	By definition, spine in MED is normal, although Schmorl bodies & irregular vertebral end plates may be observed.
GALNS GLB1	Morquio syndrome (MPS IVA & MPS IVB) (See GLB1 Disorders.)	AR	Dysostosis multiplex, odontoid hypoplasia, short stature, hepatomegaly & cloudy corneas

Gene(s)

Disorder

MOI

Clinical Features of Differential Diagnosis Disorder

Distinguishing Features/
Comment

CCN6
(WISP3)

Progressive pseudorheumatoid dysplasia (PED)

Predominant involvement of articular cartilage w/progressive joint stiffness & enlargement & w/o inflammation. Onset (age ~3-6 yrs) begins w/involvement of interphalangeal joints; later involvement of large joints & spine causes significant joint contractures, gait disturbance, & scoliosis &/or kyphosis, → abnormal posture & significant morbidity. Short stature (<3rd centile) becomes evident in adolescence.

Unlike X-linked SEDT, joint swelling & hand involvement are common features of PED.

COL2A1

SED congenita (SEDC) (See Type II Collagen Disorders Overview.)

AD ¹

Usually evident at birth w/disproportionate short stature, short extremities, broad chest, characteristic facies, myopia, & ↑ incidence of cleft palate & hearing loss. Delayed/poor ossification of vertebrae & pubic bones; long bones are short w/hypoplastic epiphyses. ↑ risk for tracheolaryngomalacia & related respiratory complications & retinal detachment. ↑ risk for cervical instability.

SED congenita is most common form of SED.

Spondyloperipheral dysplasia (See Type II Collagen Disorders Overview.)

Mild-to-moderate disproportionate short stature & short extremities, brachydactyly type E, short ulnae, variable clubfeet, cleft palate, myopia, & hearing loss; ovoid vertebra, delayed ossification of pubic bones, & flattened & irregular epiphyses in long bones. Premature hip arthrosis causes joint pain.

COL2A1
COL9A1
COL9A2
COL9A3
COL11A1
COL11A2

Stickler syndrome

AD
AR ²

Connective tissue disorder; can incl high myopia, hearing loss (both conductive & sensorineural); midfacial underdevelopment & cleft palate (either alone or as part of Pierre Robin sequence); & mild SED &/or precocious arthritis.

COL9A1
COL9A2
COL9A3
COMP
MATN3

Multiple epiphyseal dysplasia, autosomal dominant (MED)

Presents early in childhood, usually w/pain in hips &/or knees after exercise; affected children complain of fatigue w/long-distance walking; waddling gait may be present. Adult height in lower range of normal or mildly shortened; limbs relatively short compared to trunk; progressive pain & joint deformity → early-onset osteoarthritis esp of large weight-bearing joints.

By definition, spine in MED is normal, although Schmorl bodies & irregular vertebral end plates may be observed.

GALNS
GLB1

Morquio syndrome (MPS IVA & MPS IVB) (See GLB1 Disorders.)

Dysostosis multiplex, odontoid hypoplasia, short stature, hepatomegaly & cloudy corneas

From: X-Linked Spondyloepiphyseal Dysplasia Tarda

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