= DIASTROPHIC DWARFISM = EPIPHYSEAL DYSOSTOSIS

= severe rhizomelic dwarfism ← generalized disorder of cartilage followed by fibrous scars + ossifications

Genetics: autosomal recessive mutations in diastrophic dysplasia sulfate transporter gene located on chromosome 5q32–q33.1

Pathophysiology: disturbed sulfate transport → undersulfated proteoglycans in cartilage matrix

• diastrophic = “twisted” habitus; normal intellectual development
• “cauliflower ear” = ear deformity from inflammation of pinna
• laryngomalacia; lax + rigid joints with contractures
• cleft palate (25%) + micrognathia
• Axial skeleton
  • cervical spina bifida occulta
  • hypoplasia of odontoid
  • severe progressive thoracolumbar kyphoscoliosis (not present at birth) + cervical kyphosis
  • narrowed interpedicular space in lumbar spine
  • short + broad bony pelvis
  • posterior tilt of sacrum
• Extremities
  • shortening + metaphyseal widening of tubular bones
  • severe micromelia (predominantly rhizomelic = humerus + femur shorter than distal long bones):
    • short and broad femoral neck
    • coxa vara (common)
  • crescent-shaped flattened epiphysis (= retardation of epiphyseal ossification) with invagination of ossification centers into distal ends of femora
  • multiple flexion contractures (notably of major joints)
  • dislocation of one / more large joints (hip, elbow); lateral dislocation of patella
  • clubfoot = severe talipes equinovarus:
    • medially bowed metatarsals + abduction of great toes
  • deformity and shortening of metacarpals + phalanges:
    • ulnar deviation of hands
    • oval + hypoplastic 1^st metacarpal bone + abducted proximally positioned thumb = “hitchhiker's thumb” (CHARACTERISTIC)
    • bizarre carpal bones with supernumerary centers
    • widely spaced fingers

OB-US:

• proportionately shortened long bones
• abducted / hitchhiker thumb
• clubfeet
• multiple joint flexion contractures
• abnormal spinal curvature = scoliosis

Prognosis: death in infancy ← abnormal softening of tracheal cartilage