Clinical Guidance

No genotype-phenotype correlations have been identified.

Source: GeneReviews — "Chondrodysplasia Punctata 1, X-Linked"

Penetrance

Penetrance may be incomplete. ARSL pathogenic variant was identified in an affected proband and his unaffected maternal grandfather . A deletion of exons 7-10 was identified in an affected proband and his asymptomatic maternal grandfather . Considering that physical features of CDPX1 improve with age, it is uncertain whether such instances represent non-penetrance.

Source: GeneReviews — "Chondrodysplasia Punctata 1, X-Linked"

Diagnostic Criteria

Suggestive Findings

X-linked chondrodysplasia punctata 1 (CDPX1) should be suspected in a male proband with the following clinical and radiographic findings.

Clinical findings

• Brachytelephalangy (shortening of the distal phalanges)

• Nasomaxillary hypoplasia

• Hypoplasia of the anterior nasal spine

• Flattened nasal base

• Reduced nasal tip protrusion with short columella

• Crescent-shaped nostrils

• Vertical grooves within the alae nasi (in some individuals)

• Postnatal short stature

Radiographic findings

Source: GeneReviews — "Chondrodysplasia Punctata 1, X-Linked"

Differential Diagnosis

Genetic Disorders

Table 3a.

Disorders with Brachytelephalangic Chondrodysplasia Punctata (BCDP) in the Differential Diagnosis of CDPX1

Gene(s) | Disorder | MOI | Additional Overlapping Feature | Findings Distinguishing the Disorder from CDPX1

GGCX

VKORC1

| Combined deficiency of vitamin K-dependent clotting factor 1 (OMIM 277450) factor 2 (OMIM 607473) | AR | Nasal hypoplasia | Bleeding disorder due to variably levels of coagulation factors II, VII, IX, X, protein C, protein S, protein Z

MGP | Keutel syndrome (OMIM 245150) | AR | More diffuse progressive calcification of cartilage incl nose, auricles, respiratory tract

AR = autosomal recessive; CDPX1 = chondrodysplasia punctata 1, X-linked; MOI = mode of inheritance

Table 3b.

Source: GeneReviews — "Chondrodysplasia Punctata 1, X-Linked"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with X-linked chondrodysplasia punctata 1 (CDPX1), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Chondrodysplasia Punctata 1, X-Linked

Source: GeneReviews — "Chondrodysplasia Punctata 1, X-Linked"

Clinical Guidance

In individuals with cervical spine instability, extreme neck extension and neck flexion and contact sports should be avoided. In case of general anesthesia, the cervical spine should be assessed by imaging prior to the procedure.

Source: GeneReviews — "Chondrodysplasia Punctata 1, 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 1, X-Linked"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with Chondrodysplasia Punctata 1, X-Linked

Source: GeneReviews — "Chondrodysplasia Punctata 1, X-Linked"