Â鶹´«Ã½Ó³»­

Â鶹´«Ã½Ó³»­

Explore the latest content from across our publications
Join The Â鶹´«Ã½Ó³»­

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

X-linked Christianson Syndrome with Neurodegeneration and Atypical Parkinsonism in Female Carriers
Aging, Dementia, and Behavioral Neurology
Aging and Dementia Posters (7:00 AM-5:00 PM)
005
With the current pedigree and neuropathology study, we hope to explore the genetic and biochemical basis of neurodegenerative disease.
There are over 100 X chromosome loci for hereditary intellectual disability. SLC9A6 is one of the more common mutations, causing Christianson Syndrome with severe intellectual disability, seizures, and ataxia in affected males. The mutation affects NHE6, a Na/H exchanger in endosomes. It has variable spatial and temporal expression throughout life, peaking prenatally and in adulthood. Neuropathology in affected males consists of neuronal loss most prominently in the basal ganglia and cerebellum with diffuse tau deposition throughout white matter tracts. The mechanism of tau deposition in this disorder remains unclear.
We present a pedigree of a family with known SLC9A6 (NHE6) mutation with variable phenotype of mild intellectual disability or learning disorder and progressive neurodegenerative disorders in adult female members including autopsy with neuropathology for one member.
The phenotypes in females in this family are variable, ranging from very mild intellectual disability to clinical syndromes of Progressive Supranuclear Palsy and Cortical Basal Degeneration. Postmortem neuropathology was consistent with clinical findings, with tau deposition most notable in the cerebral cortex, midbrain, and pons. Interestingly, foamy histiocytes noted in the spleen and bone marrow were felt to be consistent with atypical storage disease, emphasizing the multisystem nature of genetic disease.
The penetrance of X-linked disorders in female family members is variable and incompletely understood in neuropsychiatric disorders, however family history of intellectual disability should raise suspicion for genetic etiologies of neurodegeneration. Since the presence of a genetic diagnosis may reveal unique etiology of neuronal injury, and tau deposition specifically in this Christianson Syndrome pedigree, such genetic causes and underlying pathophysiology have the potential to guide treatment in the future.
Authors/Disclosures
Micaela R. Owens, DO (Marshall University)
PRESENTER 		Dr. Owens has nothing to disclose.
No disclosure on file
Cynthia Correll, MD (Cayuga Medical Associates) Dr. Correll has nothing to disclose.