Christianson Syndrome

Christianson syndrome is an X-linked neurodevelopmental disorder caused by loss-of-function variants in SLC9A6, with severe intellectual disability, absent speech, ataxia, microcephaly, epilepsy and a happy demeanour. Males are severely affected, and carrier females may show milder features.

Pathophysiology. SLC9A6 encodes the endosomal sodium hydrogen exchanger NHE6, which regulates endosomal pH and neuronal membrane trafficking. Loss of function leads to neuronal dysfunction and progressive cerebellar and brainstem degeneration.

Presentation is in infancy with delayed development, and regression of skills can occur in childhood.

Care is supportive and addresses seizures, drooling and swallowing, mobility and sleep.

• Severe global developmental delay and absent speech
• Truncal ataxia and a wide based gait, with loss of walking in some
• Postnatal microcephaly
• Ophthalmoplegia (vertical gaze limitation) and cerebellar signs
• Epilepsy that is often difficult to treat, including myoclonic and atonic seizures
• Happy demeanour with frequent laughter
• Drooling, feeding and swallowing difficulty
• Hypotonia, spasticity, and later a movement disorder
• Sleep disturbance and behavioural problems
• Female carriers: learning difficulty and mild features, rarely severe

• SLC9A6 sequencing with deletion and duplication analysis, or exome sequencing.
• Brain MRI: cerebellar and brainstem atrophy, and white matter changes with progression.
• EEG for the seizure type.
• Developmental, swallow and ophthalmological assessment.
• Carrier testing of mothers and sisters.
• Exclusion of other causes with array and metabolic tests when the picture is atypical.

• Epilepsy: levetiracetam 10 mg/kg twice daily increasing to 30 mg/kg twice daily, valproate 10 mg/kg twice daily increasing to 20 mg/kg twice daily, clobazam 0.25 mg/kg daily increasing to 1 mg/kg daily (maximum 40 mg), lamotrigine titrated slowly, and a ketogenic diet (3:1 to 4:1 ratio) in refractory epilepsy under specialist care. Provide a rescue plan: buccal midazolam 0.3 mg/kg (maximum 10 mg) for a seizure lasting over 5 minutes.
• Drooling: glycopyrronium bromide 15 microgram/kg orally three times daily, increasing every 7 days to a maximum of 100 microgram/kg daily (not over 6 mg daily), or botulinum toxin to salivary glands.
• Feeding and swallow: swallow assessment, thickened feeds, gastrostomy for unsafe swallow, and omeprazole 0.7 to 1 mg/kg daily for reflux.
• Mobility and spasticity: physiotherapy, orthotics, and baclofen 0.3 mg/kg daily in divided doses increasing weekly to 2 mg/kg daily (maximum 60 mg).
• Sleep: sleep hygiene and melatonin 2 to 5 mg orally 30 to 60 minutes before bed (up to 10 mg if needed).
• Eye care: correction of refractive error and treatment of strabismus.
• Development and communication: early intervention, augmentative communication, and special education.
• Genetic counselling: a carrier mother has a 50% chance of transmitting the variant to each child; sons are affected and daughters are carriers.

Special groups.

• Female carriers: assess for learning and psychiatric symptoms and offer reproductive counselling.

Monitoring. Seizures, development and swallow every 3 to 6 months. Growth and nutrition at each visit, spine and hip review yearly, and eye review yearly.

Referral and escalation. Refer to clinical genetics, paediatric neurology and palliative care. Emergency for status epilepticus, aspiration or severe respiratory compromise.