About Campomelic Dysplasia

Campomelic dysplasia is typically inherited in a sporadic, autosomal dominant manner.²

Campomelic dysplasia is typically caused by a mutation in the SOX9 gene, which is located on chromosome 17q. Less frequently, a disruption of chromosome 17q may involve the SOX9 region and result in campomelic dysplasia. SOX9 is an important regulator of cartilage and sexual development.

Campomelic dysplasia is characterized by the bowing of the femur and tibia. Some individuals can have this condition without any appreciable bowing of the long bones but with other major features. These patients are referred to as having "acampomelic" camptomelic dysplasia. We will limit the following discussion to patients with classic campomelic dysplasia.

Campomelic dysplasia can be a life-limiting condition. In severe presentations, survival is sometimes possible with life-sustaining interventions. However, some children with campomelic dysplasia can survive into adulthood without the need for those interventions. In the newborn period, respiratory distress may occur due to the lack of development of the cartilage rings that support the tracheobronchial tree. Although respiratory insufficiency may lead to hypoxic brain injury, in general patients with campomelic dysplasia have typical intelligence.

Face and Skull

• Macrocephaly (unusually large head size)
• Prominent forehead
• Flat mid-face with a depressed nasal bridge
• Micrognathism
• Cleft palate (about 2/3 of children)

Trunk and Chest

• Small, narrow and bell-shaped chest

Arms and Legs

• Anterior bowing of the femur and tibia
• A subcutaneous dimple over the most prominent aspect of the bowing tibia
• Clubfeet, frequently present on both sides
• Hip dislocation

X-Ray Characteristics

• Bowing of the femur and tibia 
• Delayed ossification of distal femoral and proximal tibial epiphyses
• Cervical vertebrae as well as scapula are hypoplastic 
• Thorax is small and bell-shaped, with eleven mineralized rib pairs
• Widely spaced vertical ischia and a hypoplastic pubic bone in the pelvis
• Vertebral pedicles are hypoplastic or nonmineralized, usually in the thoracic region
• Cervical kyphosis can also be present

Long Bone Bowing

Long bone bowing in campomelic dysplasia is variable. Corrective osteotomies of the femur and tibia should be performed so that the child can start standing and walking at the appropriate times. The timing of such surgery is influenced by the child’s respiratory status. Developmental milestones are delayed in campomelic dysplasia and this should be kept in mind during decision making. A period of casting is necessary in the immediate post-operative period, followed by long-term bracing to maintain correction.

Hip Dislocations

Congenital/developmental hip dislocations are typically managed along standard lines. In infancy, the mainstay of treatment is by means of a Pavlik harness. If this fails, surgery becomes necessary.

Cervical kyphosis is an initial problem, secondary to failure of formation of the anterior cervical vertebral bodies, which can lead to spinal cord compression. Thoracic kyphoscoliosis is a severe problem that may require surgery.

Clubfeet

Clubfeet should be treated along standard lines with corrective casting and surgery, depending upon the severity of the problem.

Tracheobronchial Tree

The most significant abnormality in campomelic dysplasia is the lack of development of the cartilage rings supporting the tracheobronchial tree. These cartilage rings normally keep the breathing passages open. Poor cartilage development may cause the collapse of these passages, producing extremely small airways and causing respiratory insufficiency.

At birth, the child may require a tracheostomy and long-term ventilation at home for the first few years of life. Many do not survive past the neonatal period.

Congenital Heart Defects

Congenital heart defects were found in around 25% of cases. The most common anomaly is a patent ductus arteriosus or patent foramen ovale.

An echocardiogram should be done to evaluate for possible congenital heart disease.

Genitourinary Tract

Genitourinary Tract: Hydronephrosis (enlarged kidney), bilateral ureteral dilatation are seen in a third of patients. Hypoplastic cystic kidney, renal hypoplasia, ureteral stenosis, and renal calculi have been described in the literature. These do not pose major health risks initially but require monitoring by a nephrologist/urologist in the long term.

Sex Reversal

In some cases the lack of functioning SOX9 may lead to the failure of male genitalia. Therefore, some phenotypic females may genetically be males.

Hearing

Recurrent middle ear infections, poor development of bones that normally conduct sound (auditory ossicles), and atypical skull shape are some of the factors that contribute to hearing loss. Any suspicion of hearing loss or recurrent ear infections should prompt referral to an ENT surgeon/audiologist for further investigation.

• Respiratory distress in the newborn period.
• Chromosomal analysis should be done to evaluate for possible sex reversal in phenotypic females.
• A renal-pelvic ultrasound should be done to assess any anomalies of the genitourinary tract.
• Signs of cervical spine compression due to either cervical spine instability, cervical kyphosis or both.

1. Mansour S, Hall CM, ME Pembrey and ID Young. 1995. A Clinical and Genetic Study of Campomelic Dysplasia. J Med Gen. 32:415-420.
2. Norman, EK. Pedersen, JC. Stiris, G. Van der Hagen, CB. 1993. Campomelic dysplasia-an underdiagnosed condition? European Journal of Pediatrics. 152: 331-333.
3. Spranger JW, Brill, PW, Hall C, Nishimura G, Superti-Furga, A, Unger, S. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2018.