Campomelic syndrome is an autosomal dominant skeletal malformation syndrome characterized by shortness and bowing of long bones, especially of the lower limbs.

Autosomal dominant osteochondrodysplasia caused by mutation in the SOX9 gene (608160). (Campomelia means bowed limbs'.)

Macroscopical synopsis

 systemic anomalies

• short limb dwarfism, prenatal onset
• birth length 35-49 cm
• low-normal range birth weight
• failure to thrive in survivors
• polyhydramnios (+/- 30%)

 craniofacial anomalies

• large anterior fontanelle
• macrocephaly
• enlarged skull (large head)
• elongated skull
• large neurocranium
• small chondocrnium
• high forehead
• flat face
• small face
• micrognathia +/- Robin sequence
• low-set ears
• hypertelorism
• short palpebral fissures
• depressed nasal root
• cleft palate

 trunk anomalies

• small thoracic cage
• bell-shaped thorax
• hypoplastic scapulae
• slender ribs
• absent sternal mineralization
• eleven pairs of ribs
• hypoplastic, poorly ossified cervical vertebrae
• kyphoscoliosis
• non-mineralized thoracic pedicles
• hypoplastic thoracic pedicles
• narrow pelvis
  • narrow iliac wings
  • small iliac wings (agenesis of sacral wings)
  • widelely separated ischiae
  • relatively wide pelvic outlet
  • poorly developed ischipubic rami

 limb anomalies

• short limbs
• dislocated hips (subluxation of the hips)
• short phalanges both hands and feet
• talipes equinovarus
• small hypoplastic scapulae
• short fibula
• bowed fibula (fibular bowing)
• bowed legs
  • anterior bowing of tibia (tibial bowing)
  • mildly bowed femur (femoral bowing)

• absent ossification of proximal tibial, and distal femoral epiphysis
• cutaneous dimpling over bowed tibia (pretibial cutaneous dimples)
• clubbed feet

 visceral anomalies

• congenital heart defects
  • patent ductus arteriosus
  • ventricular septal defects
  • aortic coarctation

• tracheomalacia
• bronchomalacia (neonatal respiratory distress)
• pulmonary hypoplasia
• sex reversal in some katyotypic males (ovarian, mullerian duct, and vaginal development in XY individuals)

• urinary anomalies
  • hydronephrosis
  • hydroureters
  • medullary renal cysts
  • renal glomerular cysts (glomerulocysts)

 cerebrospinal anomalies

• hypotonia
• absent olfactory tract or absent olfactory bulbs
• hydrocephalus
• polygyria

Microscopical synopsis

 epiphyseal resting cartilage

• microscopy: unremakable
• ultrastructure: more numerous dark cells surrounded by granular and flocculent materials

 physeal growth zones:

• almost normal
• +/- mild retardation
• disorganization with osteoporosis

 no defect in bone collagen, ground substance or mineralization

Etiology

 germline mutation in the SOX9 gene (MIM.608160)
 17q rearrangements involving

• balanced t(13;17) translocation (900 Kb Upstream of SOX9) (#15717285#)
• anomalies of one or more cis-regulatory elements from an extended control region

Variants

 acampomelic campomelic dysplasia (#11754051#, #10951468#)

See also

 Osteochondrodysplasias