Table 3.

Common Conditions with Multiple Joint Problems (Laxity, Dislocations, Restriction of Joint Movement) in the Differential Diagnosis of EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity

GeneDisorder 1MOIClinical FindingsImaging Findings
B3GALT6 SEMD-JL (Beighton type), B3GALT6-related
(OMIM 271640)		AR
  • Prenatal-onset short stature
  • Facial dysmorphism (oval face, prominent forehead, prominent eyes, blue sclera, micrognathia, cleft palate)
  • Progressive kyphoscoliosis & joint dislocation
  • Progressive kyphoscoliosis
  • Ovoid vertebral bodies
  • Severe platyspondyly
  • Short, flared iliac wings
  • Radioulnar dislocation
B3GAT3 Multiple joint dislocations,
short stature, craniofacial dysmorphisms, & skeletal dysplasia ± heart defects, B3GAT3-related
(OMIM 245600)		AR
  • Short stature
  • Brachycephaly, prominent forehead
  • Multiple joint dislocations
  • Cardiac anomalies
  • Scoliosis
  • Occasionally modest platyspondyly
  • Dislocation of radioulnar & interphalangeal joints
  • Broad ilia
  • Long phalanges w/relatively short metacarpals
  • Occasionally generalized osteoporosis
B4GALT7 Ehlers-Danlos syndrome, spondylodysplastic type 1 (EDSSPD1), B4GALT7-related
(OMIM 130070)		AR
  • Short stature
  • Broad, flat forehead
  • Joint laxity & dislocations
  • Long, slender fingers & toes
  • Loose elastic skin
  • Scoliosis
  • Large joint dislocation
  • Radioulnar synostosis
CANT1 Desbuquois dysplasia,
CANT1-related
(OMIM 251450)		AR
  • Prenatal-onset short stature
  • Midface hypoplasia
  • Joint dislocations
  • Occasionally, multiple coronal clefts of vertebral bodies
  • Advanced carpal ossification
  • Monkey wrench femora
  • Hyperphalangy of index finger
CHST3 Chondrodysplasia w/
congenital joint dislocations,
CHST3-related
(See CHST3-Related Skeletal Dysplasia.)		AR
  • Short stature
  • Joint dislocations &/or restriction of joint movement
  • Clubfeet
  • Kyphoscoliosis
  • Multiple coronal clefts of vertebral bodies
  • Increase in interpedicular distance from T12 to L1 or L2
  • Bifid distal humerus
  • Accessory carpal ossification centers
GZF1 Joint laxity, short stature, & myopia (OMIM 617662)AR
  • Short stature
  • Severe myopia
  • Joint dislocation & laxity
  • Osteopenia
  • Progressive kyphoscoliosis
KIF22 SEMD-JL (Hall type or leptodactylic type),
KIF22-related
(OMIM 603546)		AD
  • Short stature
  • Knee/hip joint dislocation
  • Midface hypoplasia
  • Joint laxity
  • Genu valgum
  • Velvety skin
  • Hypotonia
  • Progressive scoliosis
  • Vertebral dysplasia (modest platyspondyly in younger persons)
  • Epimetaphyseal dysplasia (small, flat epiphyses & irregular metaphyses w/longitudinal striations)
  • Gracile, short tubular bones
NIN SEMD-JL (leptodactyly-like phenotype) 2AR
  • Microcephaly
  • Primordial short stature
  • Flat facial features
  • Joint laxity
  • Joint dislocation
  • Genu valgum
  • Pes cavus
  • Scoliosis
  • Squared vertebral bodies
  • Irregular vertebral end plates
  • Slender, short tubular bones
  • Metaphyseal striations
XYLT1 Baratela-Scott syndrome, XYLT1-related (formerly Desbuquois dysplasia type 2)
(OMIM 615777)		AR
  • Prenatal-onset short stature
  • Midface hypoplasia
  • Joint dislocations
  • Multiple coronal clefts of vertebral bodies
  • Advanced carpal ossification

AD = autosomal dominant; AR = autosomal recessive; SEMD-JL = spondyloepimetaphyseal dysplasia with joint laxity; MOI = mode of inheritance

1.

Disorder names are from the Nosology of Genetic Skeletal Disorders: 2023 Revision [Unger et al 2023].

2.

This condition is not well characterized; only one family has been reported to date [Grosch et al 2013].

From: EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity

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