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Kniest dysplasia

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Bone and Connective Tissue Disorders/Type II collagenopathies

Last updated 2mo ago

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A child has disproportionate short-trunk short stature, severely restricted joint motion with prominent knees and elbows, midface hypoplasia with cleft palate, high myopia, and progressive sensorineural hearing loss. Skeletal survey shows dumbbell-shaped femora; cartilage histology shows a "Swiss cheese" appearance.

AD; COL2A1 (type II collagen α1 chain). Most cases are caused by exon-skipping splice variants in the triple-helical domain that produce a structurally abnormal collagen, a dominant-negative ("poison-peptide") effect on trimer assembly.

  • Most cases are de novo; recurrence in unaffected parents is from gonadal mosaicism (~5%)
  • Each affected individual has 50% transmission risk to offspring

Type II collagenopathy spectrum (most → least severe):

  1. Achondrogenesis type II (Langer-Saldino): perinatal lethal
  2. Hypochondrogenesis: usually perinatal lethal
  3. Spondyloepiphyseal dysplasia congenita (SEDC): short-trunk short stature, severe myopia, hearing loss
  4. Kniest dysplasia: short-trunk short stature with severe joint involvement and "Swiss cheese" cartilage
  5. Stickler syndrome (type 1) (see stickler-syndrome): milder; orofacial cleft, myopia, hearing loss, joint hypermobility

The position and nature of the COL2A1 variant correlates broadly with where on this spectrum the patient falls.

  • Skeletal:
    • Disproportionate short-trunk short stature
    • Severe joint stiffness with prominent, knobby joints (knees, elbows): hallmark
    • Kyphoscoliosis
    • Platyspondyly (flat vertebrae)
    • Dumbbell-shaped femora on radiograph (broad metaphyses)
    • Cartilage histology: "Swiss cheese" appearance from large vacuoles within chondrocytes
  • Craniofacial:
    • Midface hypoplasia, depressed nasal bridge
    • Cleft palate (~50%) ± Pierre-Robin sequence
  • Eye:
    • High myopia (early-onset, severe)
    • Vitreoretinal degeneration → retinal detachment risk (lifelong)
    • Cataracts
  • Ear:
    • Sensorineural and conductive hearing loss
  • Respiratory:
    • Tracheomalacia, restrictive lung disease from chest wall deformity
  • Clinical + radiographic recognition (short-trunk, dumbbell femora, joint stiffness)
  • COL2A1 sequencing confirms; consider deletion/duplication if sequencing is negative
  • Cartilage biopsy is no longer routine but historically showed the diagnostic "Swiss cheese" pattern
  • Ophthalmology: baseline + lifelong dilated eye exams (retinal detachment is a major morbidity)
  • Audiology: baseline + serial hearing assessments
  • Orthopedics: scoliosis monitoring, joint care; physical therapy
  • Anesthesia precautions: difficult airway from midface hypoplasia + cervical spine instability; flag in chart
  • Cleft team if orofacial clefting
  • Genetic counseling: AD with high recurrence in offspring; gonadal mosaicism in apparently de novo families

Reference Links

GeneReviews
Nail-patella syndrome (Fong disease)Roberts syndrome (SC phocomelia)