Clinical Guidance

Variability in females. At least 95% of individuals with X-linked chondrodysplasia punctata 2 (CDPX2) are female. The clinical phenotypes in heterozygous females are highly variable and depend on the pattern of X-chromosome inactivation in relevant tissues (i.e., percentage of active X chromosomes with the pathogenic variant) and other possible modifying factors. Phenotypes range from fetal demise with multiple malformations and severe growth retardation to much milder manifestations, such as adults with only cutaneous features, short stature, or no recognizable physical abnormalities.

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"

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"

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"