[ thanatos, Greek = death; phoric, Greek = bearing]

= sporadic lethal skeletal dysplasia characterized by severe rhizomelia (micromelic dwarfism)

Prevalence: 6.9÷100,000 births; 1÷6,400–16,700 births;

• Most common lethal bone dysplasia after osteogenesis imperfecta type II

Genetics: autosomal dominant mutation of gene-encoding fibroblast growth factor receptor 3 (FGFR3)

• severe respiratory distress (early in life)
• hypotonic infants; protuberant abdomen
• extended arms + abducted externally rotated thighs
• Head
  • disproportionately large head with short base of skull + prominent forehead
  • occasionally trilobed cloverleaf skull = “Kleeblattschädel”
  • depressed nasal bridge + protruding eyes
• Chest radiograph (PATHOGNOMONIC)
  • narrow chest with normal trunk length
  • short horizontal ribs:
    • not extending beyond anterior axillary line
    • cupped anterior ends
  • short curved “telephone handle” humeri
  • H- / U-shaped vertebra plana
  • small scapula + normal clavicles
• Spine
  • normal length of trunk
  • reduction of interpediculate space of last few lumbar vertebrae
  • extreme generalized platyspondyly = severe H- / U-shaped vertebra plana
  • excessive intervertebral space height
• Pelvis (hypoplastic iliac bones)
  • iliac wings small + square (vertical shortening but wide horizontally)
  • flat acetabulum
  • narrow sacrosciatic notch
  • short pubic bones
• Extremities
  • severe micromelia:
  • bowing of extremities (type 1) / straight (type 2)
  • metaphyseal flaring = “telephone handle” appearance of long bones
  • thornlike projections in metaphyseal area
  • polydactyly

OB-US (findings may be seen very early in pregnancy):

• polyhydramnios (50–71%)
• short-limbed dwarfism with extremely short + bowed “telephone receiver”-like femurs
• extremely small hypoplastic thorax with short ribs + narrowed in anteroposterior dimension
• protuberant abdomen
• macrocrania with frontal bossing ± hydrocephalus (increased HC÷AC ratio)
• “cloverleaf skull” (in 14%) (DDx: encephalocele)
• diffuse platyspondyly
• redundant soft tissues

Prognosis: often stillborn; uniformly fatal within a few hours / days after birth ← respiratory failure

DDx:

1. Ellis-van Creveld syndrome (extra digit, acromesomelic short limbs)
2. Asphyxiating thoracic dysplasia (less marked bone shortening, vertebrae spared)
3. Short-rib polydactyly syndrome
4. Homozygous achondroplasia
5. Achondrogenesis