Campomelic Dysplasia

Bone Dysplasia Clinic

Campomelic Dysplasia

Campomelic Dysplasia has been considered to be a lethal process. It should, rather, be thought of as a ‘sublethal’ condition. This change in thinking is partly because of marked improvement in care, particularly for the respiratory complications that this disorder can cause.

In addition, there were initial ascertainment biases – more severe (and lethal) instances were recognized while milder ones were often not diagnosed or were diagnosed with a related disorder called ischio-pubic-patellar syndrome.

Primary characteristics of Campomelic Dysplasia include, among many, bowing of the femora and tibiae, pretibial skin dimples, hypoplasia of the scapulae, and, in chromosomal males, sex reversal.

Medical Issues and Parental Concerns to be Anticipated


  • Expectations: Most infants with this disorder die, apparently secondary to respiratory insufficiency. Various factors contribute to those risks (see below). Many die in the first days of life, some over the course of the first year. Even after initial survival, severe sequelae remain.  Those found to have chromosomal translocations rather than point mutations (see under Genetics and Molecular Biology below) seem to have higher probability of survival.
  • Monitoring: Anticipatory guidance and counseling of the family.
  • Intervention: In depth discussions with the family are essential, including consideration of generation of an Advance Directive, copies of which should be placed at all clinics and hospitals where the infant may be cared for.

Respiratory Problems

  • Expectations: Many factors contribute to severe respiratory risks. The chest is often markedly constricted. The airways are diminished in size and there may also be severe laryngotracheo-bronchomalacia. The mandible is often very small and subsequent retroglossia can cause upper airway obstruction. There may also be disruption of central respiratory control (central apnea) because of abnormalities of the cranial base. All may contribute to immediate neonatal risk of death and, in survivors, to long term sequelae.
  • Monitoring: Evaluation in survivors of the neonatal period should include polysomnography to look for both obstructive and central apnea as well as bronchoscopy to look directly at airways.
  • Intervention: Symptomatic management with oxygen supplementation, use of cpap or bipap, tracheostomy, long term ventilator support, etc.  Surgical chest expansion/rib interposition has not been shown to be of benefit. Airway infections should be aggressively treated. All infants with this diagnosis should be considered for RSV prophylaxis. All immunizations should be given, particularly for infections that could further compromise limited respiratory reserve (e.g. pneumococcal conjugate vaccine).

Anesthesia Risks

  • Expectations: Many infants require surgery. Risks include those related to the airway and to the cervical spine.
  • Monitoring: The cervical spine should be assessed for stability with plain lateral x-rays (flexion, neutral and extension) prior to administration of anesthesia. Flexible bronchoscopy should be done prior to intubation.
  • Intervention: Weaning and extubation frequently take longer than anticipated because of the above described respiratory risks and complications.

Central Nervous System and Development

  • Expectations: Many have structural anomalies (most commonly arhinencephaly –.  With or without structural aberrations, survivors may show serious developmental abnormalities, with profound variability from survivor to survivor. It is not clear what contributes to developmental abnormalities (primary vs. secondary to sequelae of hypoxia etc.). Cognitively normal survivors have been described.
  • Monitoring:  Formal developmental evaluation periodically throughout infancy and early childhood is warranted.
  • Intervention: Infant stimulation should begin early. Other interventions should be initiated as indicated by the periodic developmental evaluations.

Chondrocranium and Craniocervical Junction

  • Expectations: The skull base is clearly small, but little assessment has been documented. Structure suggests that there may be risk for craniocervical junction compression with secondary hypotonia and/or abnormalities of central respiratory control. There may also be risk for cervical spine instability.
  • Monitoring: Plain x-rays of the cervical spine (flexion, neutral and extension lateral views) should be completed in the first six months and, in general, about every 6-12 months thereafter. Survivors should have magnetic resonance imaging of the craniocervical junction if there is any clinical suspicion of high cervical myelopathy or evidence on polysomnography of abnormalities of central respiratory control.
  • Intervention: If craniocervical compression is documented, consider suboccipital decompressive surgery. If there is severe c-spine instability, surgical fusion may also be needed.


  • Expectations: All survivors are of small stature (sometimes markedly so).
  • Monitoring: No diagnosis specific growth grids are available. Intrinsic growth deficiency may be complicated by the cardiorespiratory problems that many have. Hormonal therapy in general is not appropriate.


  • Expectations: Scoliosis and kyphosis are exceedingly common in survivors.
  • Monitoring: Clinical monitoring at each visit. Thoracolumbar spine x-rays should be obtained if progressive scoliosis or kyphosis is detected clinically.
  • Intervention: Usual treatment is indicated; however, bracing may be problematic because of effects on respiration. 

Hip Dislocation

  • Expectations: This is quite common in newborns with this disorder.
  • Monitoring: AP and frogleg hip radiographs in infancy.
  • Intervention: Routine non-surgical orthopedic treatment is usually effective.

Lower Legs and Feet

  • Expectations: Tibial bowing is common but is often not sufficiently severe to require surgery. There may be complex alignment abnormalities of the ankle. Clubfoot is virtually constant.
  • Monitoring:  Clinical orthopedic assessment.
  • Intervention: Early initiation of passive range of motion and usual surgical intervention are appropriate for the clubfoot deformity.  Other interventions surgical intervention may also be warranted. Alignment and stability issues can be exceedingly complex and involvement of a pediatric orthopedist with experience in caring for children with dwarfing disorders is often necessary.

Radial Head Dislocation

  • Expectations: Exceedingly common, it may result in limited elbow movement.
  • Intervention: No treatment is indicated.

Cleft Palate

  • Expectations: Present in about 1/3 of infants with this disorder. Micrognathia is also quite common and at least in some the combination is appropriately designated as the Robin sequence.
  • Monitoring: Careful palatal evaluation in the neonate.
  • Intervention: Closure based on the usual criteria of age and weight is appropriate if general health status allows.


  • Expectations: This is an under-documented but serious concern. It likely arises because of a combination of structural abnormalities and recurrent middle ear dysfunction, particularly in those with cleft palate. It is likely a significant contributor to speech and language delays in survivors.
  • Monitoring: All infants should have newborn screening of hearing. Periodic behavioral testing should begin by around 9-12 months of age.
  • Intervention: Hearing aids are appropriate in those with significant hearing loss. Middle ear abnormalities (infection, fluid) should be treated aggressively, including having a low threshold for myringotomy and tube placement.

Cardiovascular Anomalies

  • Expectations: Present in about 1/4 of infants with this disorder.
  • Monitoring: Echocardiography and cardiologic assessment should be completed in infancy.
  • Intervention: Usual medical management if anomalies are discovered.

Renal Anomalies

  • Expectations: Affected children may have congenital anomalies or acquired problems secondary to vesicoureteral reflux.
  • Monitoring: Complete renal ultrasound in infancy, and probably yearly thereafter in survivors.
  • Intervention: Usual medical management if problems identified.

Gastroesophageal Reflux

  • Expectations: Present in many, this may complicate feeding and may increase risk for aspiration in pulmonologically fragile infants.
  • Monitoring: By medical history. Further assessment (swallow study and UGI) should be undertaken in those with a worrisome history. 
  • Intervention:  Consider both medical (reflux precautions, pharmacologic management) and surgical (fundoplication) treatment.  Involvement of a gastroenterologist is important given the medical complexity of these patients.

Sex Reversal

  • Expectations: Many phenotypic females are found to be 46 XY. Indeed, in around 70% of individuals with a 46 XY chromosome makeup there is complete sex reversal. In females who are 46 XY there is a high risk of gonadoblastoma. Some 46 XY males have structural genital abnormalities (such as hypospadias and/or micropenis).
  • Monitoring: Chromosomal evaluation in all babies.
  • Intervention: Early gonadectomy in all 46 XY females.

Genetics and Molecular Biology

Campomelic dysplasia is caused by abnormal functioning of a gene called SOX9. This gene codes for a transcription factor that is particularly important in bony cartilage and the testes.  Long bones are predominantly affected. The phenotypic features of campomelic dysplasia arise secondary to inactivation of one copy of the SOX9 gene. Point mutations, as well as various chromosomal rearrangements and deletions of chromosome 17, where this gene resides, have been found in individuals with campomelic dysplasia. Chromosomal assessment, comparative genomic hybridization or alternative methods to assess the 17q region probably should be completed in all affected individuals, since those with demonstrable chromosomal abnormalities seem to be less severely affected and may have a better chance for long term survival than those with point mutations within the SOX9 gene itself. The etiology of this difference remains elusive.

Most instances arise because of de novo mutations. Not surprisingly, then, recurrence risk is low, estimated to be 5% or less in subsequent pregnancies of couples who have had one affected child.  Infrequent recurrences appear to arise secondary to germinal mosaicism in either parent, to rare chromosomal rearrangements in a parent, or to exceedingly mild manifestations in a parent.  Mild cases have been described in the literature with transmission to multiple generations. If a typically affected individual lives to reproductive age, the transmission is autosomal dominant, resulting in a 50% risk that any offspring would be affected.