Christianson Syndrome

Excerpt

Clinical characteristics: Christianson syndrome (referred to as CS in this GeneReview), an X-linked disorder, is characterized in males by cognitive dysfunction, behavioral disorder, and neurologic findings (e.g., seizures, ataxia, postnatal microcephaly, and eye movement abnormalities). Males with CS typically present with developmental delay, later meeting criteria for severe intellectual disability (ID). Behaviorally, autism spectrum disorder and hyperactivity are common, and may resemble the behaviors observed in Angelman syndrome. Hypotonia and oropharyngeal dysphagia in infancy may result in failure to thrive. Seizures, typically beginning before age three years, can include infantile spasms and tonic, tonic-clonic, myoclonic, and atonic seizures. Subsequently, regression (e.g., loss of ambulation and ability to feed independently) may occur. Manifestations in heterozygous females range from asymptomatic to mild ID and/or behavioral issues.

Diagnosis/testing: The diagnosis of CS is established in a male proband by identification of a hemizygous pathogenic variant in SLC9A6 on the X chromosome and in a female proband by identification of a heterozygous SLC9A6 pathogenic variant on molecular genetic testing.

Management: Treatment of manifestations: Management of neurodevelopmental disorders, feeding difficulties, and seizures are per standard care.

Surveillance: At the time of follow-up clinical examinations, the following are recommended:

1. Measurement of weight and height (and calculation of body mass index)

2. Assessment for scoliosis/kyphoscoliosis

3. Detailed history and related assessments in adolescents and young adults for evidence of possible loss of any of the following skills: feeding, fine/gross motor skills, ambulation, and use of words/sounds

Genetic counseling: CS is inherited in an X-linked manner. The risk to sibs depends on the genetic status of the mother. Heterozygous (carrier) females have a 50% chance of transmitting the SLC9A6 pathogenic variant in each pregnancy. Sons who inherit the pathogenic variant will have CS; daughters who inherit the pathogenic variant may be asymptomatic or have mild ID and/or behavioral issues. Males with CS are not known to reproduce. Once the SLC9A6 pathogenic variant has been identified in an affected family member, carrier testing for at-risk female relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.