Objective: Expanding phenotypic spectrum in christianson syndrome (CS).

Background: CS is an X-linked neurodevelopmental disorder characterized by intellectual disability combined with microcephaly, cognitive impairment, ataxia, ophthalmoplegia and epilepsy in males. The female carrier’s phenotypic spectrum encompasses psychiatric disorders, atypical parkinsonism or no symptoms. It is caused by mutations in the SLC9A6 gene, which encodes a protein involved in endosomal trafficking.

Method: We report a male with CS and a family history of autosomal dominant Parkinson’s disease (PD). We assessed the clinical, neuroimaging and genetic features.

Results: A 40-year-old male presented for evaluation for parkinsonism. He was born at term without complications and had mild delayed learning milestones. At the age of 17, he developed upper limbs dystonia and his family noticed slowness of movements when he was 30 years old. He had initial good response to dopaminergic therapy, but he developed dysphagia, urinary incontinence and cognitive impairment. Currently, he is dependent on daily living activities. The family history was positive for PD in his mother, maternal grandfather and maternal great-grandmother. His mother presented with a late-onset and levodopa-responsive PD, without neuropsychiatric symptoms. Examination was remarkable for vertical supranuclear gaze palsy and pathological saccadic eye movements. Hypomimia, asymmetric parkinsonism, freezing of gait, postural instability and hyperreflexia were apparent, without cerebellar signs. The neuropsychological testing showed cognitive impairment with deficits in attention, executive and visuospatial functions. Brain MRI was normal, while 123FP-CIT SPECT showed nigrostriatal pathway degeneration. The investigations done to rule out secondary parkinsonism were unremarkable. Whole exome sequencing demonstrated a hemizygous c.767G>A (p.S256N) pathogenic variant in the SLC9A6 gene at Xq26.3. At the same time, G2019S LRRK2 mutation was detected in his mother responsible for her PD. This mutation was not present in the index case.

Conclusion: So far, there are less than 100 patients reported with a clinical diagnosis of X‐linked CS. This is the second case of atypical parkinsonism as a rare manifestation of CS in males and provides an interesting family to study for a better phenotype characterization of this rare syndrome.

References: [1] Pescosolido MF, Kavanaugh BC, Pochet N, et al. Complex Neurological Phenotype in Female Carriers of NHE6 Mutations. Mol Neuropsychiatry. 2019;5(2):98–108. [2] Sinajon P, Verbaan D, So J. The expanding phenotypic spectrum of female SLC9A6 mutation carriers: a case series and review of the literature. Hum Genet. 2016;135(8):841–850. [3] Chandra S, Rao K, A. Ghosh A, Ray J, Northrup H, Stimming E. Parkinsonism in Christianson Syndrome: A Unique Presentation of a Unique Syndrome [abstract]. Mov Disord. 2018; 33 (suppl 2) [4] Ieda D, Hori I, Nakamura Y, et al. A novel splicing mutation in SLC9A6 in a boy with Christianson syndrome. Hum Genome Var. 2019;6:15.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/atypical-parkinsonism-due-to-a-mutation-in-the-slc9a6-gene/