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Cranioectodermal Dysplasia

Last updated Aug. 15, 2018

Approved by: Maulik P. Purohit MD, MPH

Cranioectodermal Dysplasia (CED) is a rare genetic disorder. It may be caused by mutation(s) in one of the 4 genes associated with the disorder: WDR35, WDR19, IFT122, and IFT43 gene.


What are the other Names for this Condition? (Also known as/Symptoms)

  • CED (Cranioectodermal Dysplasia)
  • Levin Syndrome I
  • Sensenbrenner Syndrome

What is Cranioectodermal Dysplasia? (Definition/Background Information)

  • Cranioectodermal Dysplasia (CED) is a rare genetic disorder. It may be caused by mutation(s) in one of the 4 genes associated with the disorder: WDR35, WDR19, IFT122, and IFT43 gene
  • These mutations account for roughly 40% of the reported cases, and the condition is inherited in an autosomal recessive pattern. In cases where no mutation is seen, the cause of Cranioectodermal Dysplasia is unknown
  • These genes code for protein subunits of the intraflagellar transport-A (IFT-A) complex, which is involved in the assembly of ciliary units. The cilia are microscopic hair-like structures present on the surface of cells that are necessary for the proper development of skeletal structure, skin, hair and many organs. When mutations occur in these genes, ciliary assembly is affected, which in turn affects many systems in the developing fetus
  • The signs and symptoms of Cranioectodermal Dysplasia may include abnormal bone development, abnormal facial features, kidney malfunction, enlarged liver, liver malfunction, respiratory distress, and congenital heart defects, among others
  • An accurate diagnosis after birth may require a physical examination, an evaluation of family history, skeletal and organ imaging, including urine and blood tests. Cranioectodermal Dysplasia may be diagnosed prenatally, if there is a known family history of CED
  • The treatment options for Cranioectodermal Dysplasia include correction of the skeletal abnormalities through surgery, medication for organ dysfunction, physical therapy, growth hormone treatment, and special education amongst others
  • The prognosis of Cranioectodermal Dysplasia is poor with many newborns and young children succumbing to renal, as well as respiratory failures. A very small percentage of the affected individuals have been reported to reach young adulthood

Who gets Cranioectodermal Dysplasia? (Age and Sex Distribution)

  • Cranioectodermal Dysplasia is known to be a rare genetic condition. The exact prevalence of CED is currently not known. To date, less than 60 cases have been reported in the scientific literature
  • The condition manifests at birth and the newborn child may present with signs and symptoms of CED
  • Both males and females are affected
  • No particular racial and ethnic preference is noted

What are the Risk Factors for Cranioectodermal Dysplasia? (Predisposing Factors)

  • Cranioectodermal Dysplasia is a genetic disorder, and so, having a family history of the condition is a key risk factor for a child to be born with CED

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cranioectodermal Dysplasia? (Etiology)

  • In 40% of the individuals with Cranioectodermal Dysplasia, the disorder is caused by mutation(s) in any of the following 4 genes: WDR35, WDR19, IFT122, and IFT43
    • Each of the causative genes codes for a protein that forms a subunit of a complex known as the intraflagellar transport-A (IFT-A) complex
    • The IFT-A protein complex is a component of cilia, which are microscopic hair-like structures observed in almost all mammalian cells. The cilia are important for the proper development of many different types of tissue, including the bones, skin, many organs and tissues
    • The IFT-A complex, as the name suggests, is involved in transport of substances from the tip of the cilia to their bases, which is necessary for the assembly of ciliary structures
    • A mutation in one of the 4 genes (WDR35, WDR19, IFT122, and IFT43) may lead to a dysfunctional or abnormal subunit. This results in aberrant assembly of the IFT-A complex leading to ciliary malformations
    • The exact mechanism of how the abnormal cilia leads to the abnormalities observed with CED is currently unclear
  • Cranioectodermal Dysplasia is inherited in an autosomal recessive pattern. This indicates that an individual must have both copies of the causative gene to be defective in every cell of the body, in order for the disease to manifest itself
  • The cause of Cranioectodermal Dysplasia in individuals without a mutation in one of the aforementioned genes is not known

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Cranioectodermal Dysplasia?

The type and severity of signs and symptoms in individuals with Cranioectodermal Dysplasia can vary, even if they belong to the same family. The signs and symptoms of CED may include:

  • Skeletal defects such as:
    • Long head (dolichocephaly) owing to abnormal fusion of skull bones (sagittal craniosynostosis)
    • Funnel chest (pectus excavatum); narrow thorax (between the neck and abdomen)
    • Short femur
    • Short, stubby fingers and toes (brachydactyly)
    • Fused fingers/toes (syndactyly); curved fingers/toes (clinodactyly)
    • Very elastic joints that can extend abnormally
  • Abnormal facial features:
    • Prominent forehead
    • Abnormally wide space between the inner corners of eyes (telecanthus)
    • Upslanted or downslanted eyes; extra skin in the eyelid (epicanthal fold)
    • Ears that are located low on the head; ears that are rotated backwards
    • Upturned nostrils
    • Missing or small teeth
    • Sparse hair
  • Kidney malfunction resulting in:
    • Large amounts of dilute urine
    • Excessive thirst
    • Weakness and listlessness
  • Liver abnormalities causing:
    • Fibrosis of liver
    • Enlarged liver
    • Increased amount of bilirubin in blood
  • Frequent respiratory tract and lung infections
  • Asthma
  • Cardiac abnormalities such as septal defects

How is Cranioectodermal Dysplasia Diagnosed?

An accurate diagnosis of Cranioectodermal Dysplasia may be made through the following:

  • Physical examination and assessment of family medical history
  • Imaging studies, such as computed tomography (CT) scans, X-ray and ultrasonography, to check for skeletal and organ abnormalities
  • Testing the eyes for any eye defects
  • Urine test to check for kidney function
  • Blood tests to check for liver function
  • Consultation with cardiac and pulmonary specialists for abnormalities of the heart and lungs
  • Kidney and liver biopsy to determine the extent of damage to the organs
  • Genetic testing to check for mutation in the 4 causative genes, namely, WDR35, WDR19, IFT122, and IFT43 genes

When there is a family history of CED, prenatal testing, with fetal ultrasound in the second trimester of pregnancy, followed by genetic testing for confirmation may be undertaken.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cranioectodermal Dysplasia?

Some of the potential complications in individuals with Cranioectodermal Dysplasia may include:

  • Kidney failure and end-stage kidney disease
  • Fibrosis of the liver
  • Frequent lung infections, pneumonia
  • Defective heart function

How is Cranioectodermal Dysplasia Treated?

The treatment options for Cranioectodermal Dysplasia can include the following:

  • Surgery to correct skeletal abnormalities
  • Growth hormone therapy
  • Physical therapy
  • Oral medication and supplements for renal insufficiency
  • In newborns with respiratory distress, mechanical ventilation may be required
  • Prophylactic antibiotics for frequent respiratory tract infections
  • In case asthma develops, steroid treatment may be recommended
  • Dental care to correct tooth abnormalities
  • Vision care and aids, if vision is impaired
  • In case of kidney failure, dialysis may be needed
  • For end-stage renal disease, kidney transplantation may be required
  • Special education
  • Monitoring of health with recommended follow-up checks

How can Cranioectodermal Dysplasia be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Cranioectodermal Dysplasia, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Cranioectodermal Dysplasia
  • Regular medical screening at periodic intervals with tests, and physical examinations are highly recommended

What is the Prognosis of Cranioectodermal Dysplasia? (Outcomes/Resolutions)

  • The prognosis of Cranioectodermal Dysplasia is poor, as many children die from the disorder due to respiratory failure, pneumonia, heart conditions, and kidney malfunction
  • Those who survive infancy may require frequent medical intervention and hospitalizations
  • A very low percentage of affected individuals are reported to reach young adulthood

Additional and Relevant Useful Information for Cranioectodermal Dysplasia:

  • Differential diagnosis of Cranioectodermal Dysplasia includes Jeune syndrome, from which it can be distinguished by the presence of craniosynostosis, and skin and dental dysplasia
  • CED also overlaps with Ellis van Creveld syndrome, which also shows ectodermal defects and narrow thorax

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: July 22, 2016
Last updated: Aug. 15, 2018