Clinical characteristics: X-linked chondrodysplasia punctata 1 (CDPX1) is characterized by chondrodysplasia punctata (stippled epiphyses), brachytelephalangy (shortening of the distal phalanges), and nasomaxillary hypoplasia. Although most affected males have minimal morbidity and skeletal findings that improve by adulthood, some have significant medical problems including respiratory involvement, cervical spine stenosis and instability, mixed conductive and sensorineural hearing loss, and intellectual disability.
Diagnosis/testing: The diagnosis of CDPX1 is established in a male proband with typical clinical and radiographic findings and a hemizygous ARSL pathogenic variant identified by molecular genetic testing. Testing of ARSL enzymatic activity is not currently available on a clinical basis.
Management: Treatment of manifestations: Treatment of respiratory difficulty as per ENT and/or pulmonologist including nasal stents and oxygen as needed. Severe maxillary hypoplasia or maxillary retrognathia may require reconstructive surgery in older individuals. Instability of the cervical spine may require a cervical collar or spinal fusion. Decompression for cervical spine stenosis as needed. Hearing aids and pressure equalization tubes may be needed for hearing loss. Therapies and individualized education plan for those with developmental delay and/or learning disorder. Standard treatment for vision issues and cardiac anomalies.
Surveillance: Routine monitoring for growth deficiency, scoliosis, hearing loss, developmental delay, and ocular abnormalities. Assess for cervical spine instability by flexion-extension radiographs every six to twelve months until growth is completed.
Agents/circumstances to avoid: 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.
Genetic counseling: CDPX1 is inherited in an X-linked manner. If the mother of a proband has the ARSL pathogenic variant identified in the proband, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and thus far have not been affected. Males with CDPX1 pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing for at-risk relatives and prenatal testing for at-risk pregnancies are possible if the ARSL pathogenic variant has been identified in the family.
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