Cranioectodermal dysplasia

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 1515

Definition

Cranioectodermal dysplasia (CED) is a rare developmental disorder characterized by congenital skeletal and ectodermal defects associated with dysmorphic features, nephronophthisis, hepatic fibrosis and ocular anomalies (mainly retinitis pigmentosa).

Epidemiology

To date, 20 cases have been reported in the literature.

Clinical description

CED is primarily characterized by an abnormal development of bones (i.e. craniosynostosis/dolichocephaly, narrow thorax, pectus excavatum , rhizomelic micromelia, brachydactyly, syndactyly, clinodactyly, hyperextensible joints), and ectodermal defects such as dental anomalies (reduced enamel thickness, hypodontia, microdontia, taurodontism, malformations of the cusps), sparse hair, and abnormal finger and toe nails. Dysmorphic features are observed such as epicanthic folds, hypotelorism, anteverted nares, and everted lower lip. Patients frequently develop chronic renal failure due to nephronophthisis, usually between the ages of 2 and 6. Liver involvement (hepatic fibrosis) can also be observed. Recurrent lung infections, heart defects and ocular anomalies (nystagmus, myopia, retinal dystrophy, and particularly retinitis pigmentosa) are also possible in the course of the disease.

Etiology

CED is a heterogenous condition belonging to the ciliopathy group of diseases and is due to mutations in the IFT122 , IFT43 , WDR19 and WDR35 genes involved in intraflagellar transport (IFT). This genetic background explains the pleiotropic phenotype of CED that includes manifestations of several ciliopathies.

Diagnostic methods

Diagnosis is based on clinical examination. Imagery (ultrasonography), laboratory findings (urine analysis, serum electrolytes, and lipid profile), histological examination and liver and renal function tests allow detection of potential renal and liver anomalies. Ocular anomalies can be detected by eye fundus and electroretinography.

Differential diagnosis

Differential diagnosis of CED includes Jeune syndrome (see this term) from which it can be distinguished by the presence of craniosynostosis, and skin and dental dysplasia. CED also overlaps with Ellis van Creveld syndrome (see this term) which also shows ectodermal defects and narrow thorax.

Genetic counseling

In most cases, transmission is autosomal recessive.

Management and treatment

In many cases, renal function rapidly deteriorates, requiring treatment of metabolic acidosis, oral sodium chloride supplementation, then dialysis or renal transplantation in case of end-stage renal failure.

Prognosis

Prognosis depends on renal, heart and lung defects which can be life threatening.

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