Christianson syndrome is an X linked syndrome associated with intellectual disability, microcephaly, seizures, ataxia and absent speech.
Presentation
Onset of symptoms is normally within the first year of life with truncal
ataxia
Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
and
seizure
A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
s. The head is small (
microcephaly
Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it m ...
). Common facial abnormalities include:
* Long narrow face
* Prominent nose
* Prominent jaw
* Open mouth
Other common features include:
* Uncontrolled drooling
* Abnormal eye movements
The associated intellectual disability is usually in the profound range.
Those affected often have a happy demeanor with frequent smiling and spontaneous laughter.
Genetics
This condition is caused by mutations in the ''
SLC9A6
Sodium/hydrogen exchanger 6 is an integral membrane protein that in humans is encoded by the ''SLC9A6'' gene. It was originally thought to be a mitochondrial-targeted protein, but subsequent studies have localized it to the plasma membrane and re ...
'' gene. This gene is located on the long arm of the
X chromosome
The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...
(Xq26.3). The gene encodes a
sodium
Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...
/
hydrogen
Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...
exchanger located in the
endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membra ...
s. Mutations in this gene cause a decrease in the pH (overacidification) of the endosomes.
How this causes the clinical features is not known presently. The inheritance of this condition is X-linked dominant.
Diagnosis
The diagnosis may be suspected on clinical grounds. It is made by sequencing the SLC9A6 gene.
Differential diagnosis
*
Angelman syndrome
Angelman syndrome (AS) is a genetic disorder that affects approximately 1 in 15,000 individuals. AS impairs the function of the nervous system, producing symptoms, such as severe intellectual disability, developmental disability, limited to no ...
*
Spinocerebellar ataxia type 29
Management
There is presently no curative treatment. Management is supportive.
Epidemiology
The prevalence is not known but this is considered to be a rare disease.
History
This condition was first described in 1999.
[Christianson AL, Stevenson RE, van der Meyden CH, Pelser J, Theron FW, van Rensburg PL, Chandler M, Schwartz CE (1999) X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27. J Med Genet 36:759–766] The causative mutation was discovered in 2008.
[Gilfillan GD, Selmer KK, Roxrud I, Smith R, Kyllerman M, Eiklid K, Kroken M, Mattingsdal M, Egeland T, Stenmark H, Sjøholm H, Server A, Samuelsson L, Christianson A, Tarpey P, Whibley A, Stratton MR, Futreal PA, Teague J, Edkins S, Gecz J, Turner G, Raymond FL, Schwartz C, Stevenson RE, Undlien DE, Strømme P (2008) SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet 82:1003–10]
References
{{Medicine, state=collapsed
Rare syndromes