Connexion

GENATLAS PHENOTYPE

last update : 13-11-2013

Symbol	ISSX
Location	Xp22.13
Name	infantile spasms syndrome with hypsarrhythmia
Other name(s)	West syndrome, infantile encephalopathy with seizures
Corresponding gene	ARX , CDKL5
Other symbol(s)	XMESID
Main clinical features	early onset seizures before the age of 3 months, including myoclonic epilepsy with spasticity and mental retardation, Rett-like lacking early normall period significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome
Genetic determination	sex linked
Related entries	RTTA
Function/system disorder	neurology
Type	disease

Gene product

Name

. aristaless related homeobox . cyclin-dependent kinase-like 5

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

frameshift		truncated protein	resulting in exon skipping in CDKL5
missense		abnormal protein/loss of function	disruption of DNA binding or protein stability
missense			within the homeodomain of ARX
	translocation		t(X;A) with CDKL5 disruption
various types			mostly truncating mutations

Remark(s)

expansion of the first alanine tract of ARX (binding of these expanded polyalanine tract mutant ARX proteins to IPO13 may be less efficient than that of the normal ARX protein and may lead to compromised nuclear import, contributing in part to the molecular pathogenesis of these disorders)

expansion of pA2 of ARX beyond 20 residues with dup27 bp mutation expands pA2 from 12A to 21A and resulting phenotype for hemizygous c.430_456dup(27 bp) males is infantile spasms with a consistent early age of onset (2 months) and death early in life (Reish 2009)