Chondrodysplasia Punctata 1, X-linked Recessive

X-linked chondrodysplasia punctata 1 (CDPX1), a congenital disorder of bone and cartilage development, is caused by a deficiency of the Golgi enzyme arylsulfatase E (ARSE). It 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 compromise, cervical spine stenosis and instability, mixed conductive and sensorineural hearing loss, and intellectual disability. Diagnosis/testing. In approximately 25% of individuals with features of CDPX1, routine karyotype analysis reveals deletions or rearrangements of the short arm of the X chromosome (Xp) that include ARSE. Chromosomal microarray (CMA) can be used to evaluate for smaller interstitial deletion syndromes. Sequence analysis of ARSE identifies a pathogenic variant in up to 60% to 75% of males who meet clinical diagnostic criteria. Management. Treatment of manifestations: Respiratory difficulty can require frequent monitoring, nasal stents, and oxygen. 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. Surveillance: Routine monitoring of hearing, growth, development, and cervical spine instability. Genetic counseling. CDPX1 is inherited in an X-linked manner. If the mother of a proband has the ARSE 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 ARSE pathogenic variant has been identified in the family.