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A rare developmental defect during embryogenesis characterized by intellectual deficit, ataxia, postnatal microcephaly, and hyperkinesis.
ORPHA:85278Classification level: Disorder
Christianson syndrome (CS) prevalence is estimated to affect 1 in 16,000 to 100,00 males worldwide.
Affected males diagnosed with CS typically present with the following core diagnostic features: nonverbal status, intellectual disability (ID), epilepsy, ataxia, postnatal microcephaly, and hyperkinesis. Seizures typically occur prior to the age of three. Secondary symptoms include behaviors associated with autism, Angelman syndrome features, eye movement problems (e.g. strabismus), hypotonia, gastroesophageal reflux disease (GERD), regressions (especially after the 1st decade of life), low height and/weight (progressing with age), and cerebellar vermal atrophy (particularly after the 1st decade). Females with heterozygous NHE6 mutations may present with a wide ranging phenotype ranging from unaffected to more severe neurologic/psychiatric manifestations.
Christianson syndrome is caused by loss-of-function mutation of the SLC9A6 gene (Xq26.3), which encodes the endosomal Na+/H+ Exchanger 6 (NHE6) protein.
CS diagnosis is confirmed by molecular genetic testing. Core diagnostic symptoms include nonverbal status, ID, epilepsy, ataxia, postnatal microcephaly, and hyperkinesis.
Differential diagnoses include Angelman syndrome and ID (especially if it appears to follow an X-linked pattern).
Prenatal genetic testing is possible if the familial mutation is known.
Genetic counseling is advised. Heterozygous females have a 50% chance of transmitting the pathogenic variant in pregnancy.
Management and treatment
Management of symptoms associated with seizures, ID/developmental delay, motor deficits, feeding difficulties, and/or eye problems is common. No specific treatment exists.
Progressive symptoms appear to progress as males age, especially after the 1st decade of life. These include regressions (e.g. walking, talking, and fine/gross motor skills), cerebellar atrophy, and low height/weight. Despite reports of premature mortality in CS males (i.e. ranging from approximately 20-50 years), life expectancy is currently unknown.