[MIM 300 243]

(X-linked intellectual disabilities -  craniofacial abnormalities - epilepsy - ophthalmoplegia - cerebellar atrophy; X-linked intellectual deficiency South Africa type)

 Extremely rare: reported in a few families (fewer than 50 individuals, mostly in South Africa in a population of Norwegian origin). Loss-of-function mutation or deletion of the SLC9A6 gene (Xq26.3) coding for the endosomal Na+/H+ exchanger 6 (NHE6). 

A rare X-linked syndromic form of intellectual disability characterized by :

-         severe developmental delay or regression, 

-         early-onset epilepsy

-         non-verbal language

-         ataxia 

-         microcephaly,

-         hyperkinesia

Male patients are severely affected: profound intellectual deficit, microcephaly, mutism, early-onset epilepsy of varying types, abnormal movements, developmental delay and hypotonia. Other manifestations include ophthalmoplegia (68 %), truncal or gait ataxia, dystonia with stereotyped hand movements, frequent smiling with episodes of uncontrolled laughter (62 %), autistic-like behavior disorder (18 %), open mouth, significant salivary incontinence and swallowing difficulties (44 %), gastro-oesophageal reflux (56 %) and gracile habitus. Pain perception threshold is higher than normal (78 %). In 30 % of cases, symptoms are similar to Angelman syndrome (see this term)

Progressive loss of weight for height. Death usually between the ages of 25 and 30 years of age.

MRI: hypoplasia or aplasia of the cerebellum, dilation of ventricles secondary to cerebral atrophy, thin corpus callosum.

Intellectual deficit has been reported in some women (carriers).

Symptomatology Similar to Angelman syndrome (see this term)

Anesthetic implications: 

swallowing disorders, epilepsy, gastro-esophageal reflux; high threshold for pain.

References : 

-        Kavanaugh BC, Elacio J, Best CR, St Pierre DG, Pescosolido MF et al.
Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults.
J Med Genet 2024;61:1031-9. doi:10.1136/jmg-2024-109973

Updated: February 2025