Clinical Guidance

Null EBP variants are associated with a severe CDPX2 phenotype in females and result in intrauterine lethality in males (except in a mosaic state). Hypomorphic hemizygous EBP variants are associated with a milder MEND phenotype in males .

Source: GeneReviews — "Chondrodysplasia Punctata 2, X-Linked"

Penetrance

A few clinically unaffected females with molecularly confirmed CDPX2 have been reported . However, these females were ascertained from segregation testing, and phenotyping may not have been as comprehensive as in the proband. Some women have been so mildly affected that they were identified only after having had a child with more severe features in whom CDPX2 was diagnosed. Although these adult women have subtle findings, their findings are sufficient to consider them affected.

Source: GeneReviews — "Chondrodysplasia Punctata 2, X-Linked"

Diagnostic Criteria

X-linked chondrodysplasia punctata 2 (CDPX2) is a skeletal dysplasia that also affects the skin and eyes. Specific diagnostic criteria for CDPX2 have not been published. Classic CDPX2 occurs almost exclusively in females. There are reports of affected males with an XXY karyotype or with somatic mosaicism who have clinical manifestations similar to affected females.

Suggestive Findings

CDPX2 should be suspected in an individual with the following clinical findings:

Source: GeneReviews — "Chondrodysplasia Punctata 2, X-Linked"

Differential Diagnosis

Several disorders demonstrate features similar to those of X-linked chondrodysplasia punctata 2 (CDPX2) and/or manifest stippling on radiographs and various combinations of limb asymmetry, short stature, intellectual disability, cataracts, and skin changes. The key radiologic finding of chondrodysplasia punctata occurs in various metabolic disorders, skeletal dysplasias, chromosome abnormalities, and teratogenic exposures.

Genetic Disorders

Table 3.

Disorders and Genes of Interest in the Differential Diagnosis of Chondrodysplasia Punctata 2, X-Linked

Differential Diagnosis Disorder | Gene(s) | MOI | Features of the Differential Diagnosis Disorder

Overlapping w/CDPX2 | Distinguishing from CDPX2

Skeletal dysplasia w/radiographic evidence of CDP1

Source: GeneReviews — "Chondrodysplasia Punctata 2, X-Linked"

Management Guidelines

No published guidelines exist to establish the extent of disease or proper management in an individual with X-linked chondrodysplasia punctata 2 (CDPX2). The following recommendations are based on current literature and the authors' experience. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CDPX2, the evaluations summarized (if they have not already been completed) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Chondrodysplasia Punctata 2, X-Linked

Source: GeneReviews — "Chondrodysplasia Punctata 2, X-Linked"

Clinical Guidance

Adequate sun protection is recommended for individuals with ichthyosis, who are at risk of dehydration secondary to overheating during prolonged sun exposure. Furthermore, care must be taken with use of emollients (which are oil based) and direct sun exposure, which can lead to sunburn.

Source: GeneReviews — "Chondrodysplasia Punctata 2, X-Linked"

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 — "Chondrodysplasia Punctata 2, X-Linked"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with Chondrodysplasia Punctata 2, X-Linked

Source: GeneReviews — "Chondrodysplasia Punctata 2, X-Linked"