Clinical Guidance

No genotype-phenotype correlations have been documented to date. Some case reports claim a more severe phenotype for deletions or splice site variants in the central region of the gene (exons 24-35) (this remains unconfirmed) . In addition, phenotypic variability between and within families is wide, independent of the variant type (splice site or missense) . state that individuals with a confirmed FBN2 (likely) pathogenic variant have a higher clinical score than those without an FBN2 (likely) pathogenic variant (P0.001). Nevertheless, persons without an FBN2 (likely) pathogenic variant but with a clinical score as high as 19 have been reported, making it impossible to clinically differentiate between individuals with and without an FBN2 (likely) pathogenic variant.

Source: GeneReviews — "Congenital Contractural Arachnodactyly"

Penetrance

The penetrance for CCA is likely up to 100%, but some disease manifestations, including the ear and joint manifestations, may become less obvious with age. Nevertheless, upon careful examination, less than 1.2% of the variability of the clinical score could be attributed to age . Indeed, a previous report indicates that the diagnosis was often retrospectively made in one parent of a proband due to mild features still evident in adulthood (mild contractures without any functional impairment and/or prominent helical crus and anterior antihelical crus ["tram track" ears]) . In addition, long-bone overgrowth and scoliosis may become more prominent with age. Clinical manifestations are the same in males and females.

Source: GeneReviews — "Congenital Contractural Arachnodactyly"

Diagnostic Criteria

Formal diagnostic criteria for congenital contractural arachnodactyly (CCA) have not been established.

Suggestive Findings

Classic CCA should be suspected in individuals with the following:

• Arachnodactyly with positive wrist and thumb sign

• Flexion contractures of multiple joints including elbows, knees, hips, ankles, and/or fingers

• Kyphoscoliosis (usually progressive)

• Abnormal pinnae ("crumpled" outer helices)

• A marfanoid habitus (a long and slender build, dolichostenomelia, pectus deformity, muscular hypoplasia, highly arched palate)

On rare occasions, infants were reported with the clinical findings of classic CCA as well as the following anomalies [, , , , ]:

Source: GeneReviews — "Congenital Contractural Arachnodactyly"

Differential Diagnosis

Disorders with features that overlap with those of congenital contractural arachnodactyly (CCA) are summarized in . Table 4. Disorders to Consider in the Differential Diagnosis of Congenital Contractural Arachnodactyly (CCA)

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with congenital contractural arachnodactyly (CCA), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Classic Congenital Contractural Arachnodactyly

Source: GeneReviews — "Congenital Contractural Arachnodactyly"

Clinical Guidance

Avoid contact sports and activities that stress joints. Individuals should remain active but avoid high-intensity aerobic activities. LASIK eye surgery may increase the risk for keratoconus in individuals with predisposing ocular conditions.

Source: GeneReviews — "Congenital Contractural Arachnodactyly"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Congenital Contractural Arachnodactyly"

Surveillance Guidelines

Table 9. Recommended Surveillance for Individuals with Classic Congenital Contractural Arachnodactyly

Source: GeneReviews — "Congenital Contractural Arachnodactyly"