Congenital contractural arachnodactyly (ORPHA:115)
A rare connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, kyphoscoliosis, abnormal pinnae and muscular hypoplasia.
Epidemiology
The incidence of congenital contractural arachnodactyly (CCA) is unknown and its prevalence is difficult to estimate due to the overlap in phenotype with MFS. About 70 probands have been described with no geographical predilection.
Clinical description
CCA often presents at birth with congenital contractures, 'crumpled' ear helices, arachnodactyly, and a lean body habitus. Congenital scoliosis is rare. Over the years, the congenital contractures and ear malformations tend to improve, but usually remain noticeable, as well as a lean body habitus. The external ear in adults often shows a prominent anterior crus of the antihelix resulting in a 'tram tracks' appearance with the helical crus. Individuals with CCA are at risk for developing mitral valve prolapse and aortic root dilatation, but the exact risk for complications is unknown but esteemed low. Ocular complications include keratoconus. Ectopia lentis has not been confirmed in individuals with a molecularly proven diagnosis. At the mildest end, parents who are diagnosed retrospectively upon evaluation of their more severely affected child may show a lean body build, mild arachnodactyly, prominent anterior crus of the antihelix, and/or mild contractures without impairment. At the most severe end congenital heart defects and gastrointestinal malrotation and atresia have been documented, though a clear correlation with the genotype remains to be established.
Etiology
CCA is caused by a mutation in the FBN2 gene on chromosome 5q23.
Diagnostic methods
During pregnancy, ultrasound imaging may be used to demonstrate joint contractures and hypokinesia in suspected cases. A clinical scoring system for CCA has been published and can be used for the diagnosis of probands: arachnodactyly, camptodactyly, large joint contractures are each allotted 3 points, dolichostenomelia and pectus deformity are allotted 2 points, (kypho)scoliosis, muscle hypoplasia, highly arched palate, and micrognathia are allotted 1 point. A score of 7 points or more indicates a likely diagnosis of CCA. Confirmation with molecular analysis is advised.
Differential diagnosis
Although the clinical features can be similar to Marfan syndrome (MFS), multiple joint contractures (especially of the elbow, knee, and finger joints), and crumpled ears in the absence of significant aortic root dilatation are characteristic of CCA. Crumpled ears can be present in neonatal MFS, that however additionally shows severe valvular disease and/or aortic dilatation.
Antenatal diagnosis
Antenatal diagnosis is possible where the pathogenic variant has previously been identified in a family member.
Genetic counseling
Transmission is autosomal dominant. Genetic counseling should be offered to at risk individuals informing them that there is a 50% risk of having an affected child at each pregnancy.
Management and treatment
Management of children with CCA is symptomatic. Early physiotherapy for contractures and scoliosis can prevent morbidity later in life. Cardiac and ophthalmologic evaluations are recommended.
Prognosis
Spontaneous improvement in camptodactyly and contractures is observed but residual camptodactyly usually remains. Ear malformations tend to improve. Joint pain may occur later in life and scoliosis can, rarely, be disabling. The risk for aortic dissection has not been established.

                            Last update: 
                            October 2023


                            - Expert reviewer(s): 
                            Pr Bert CALLEWAERT | VASCERN*


                                * European Reference Network