Epileptic Encephalopathy, Early Infantile, 1

Alternative Names

  • EIEE1
  • Infantile Spasm Syndrome, X-Linked 1
  • ISSX1
  • West Syndrome, X-Linked
  • Infantile Epileptic-Dyskinetic Encephalopathy
  • XMESID
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WHO-ICD-10 version:2010

Diseases of the nervous system

Episodic and paroxysmal disorders

OMIM Number

308350

Mode of Inheritance

X-linked recessive

Gene Map Locus

Xp22.13

Description

Infantile Spasm Syndrome (West Syndrome) is responsible for almost 25% of epilepsies with onset in the first year of life. The condition is typified by the triad of infantile spasms, abnormal and chaotic brain wave patterns, called hypsarrythmia, and mental retardation. The onset of ISSX is generally within the first year of life. The characteristic spasms begin immediately after sleep arousal, and are typically symmetrical, bilateral, brief, and sudden contractions of the axial muscle groups. Although these spasms usually stop by the age of five years, other, more severe seizure types may take over in over half of the affected patients. Worldwide, about 20 in every 100,000 children born are affected by this condition.

CT and MRI scans are used to diagnose this condition in children with spasms. Differentials to be considered include exaggerated startle responses, benign myoclonus of early infancy, myoclonic ecstatic epilepsy, and Sandifer syndrome. Earlier forms of treatment used to focus on corticosteroids such as ACTH and prednisolone. However, newer anticonvulsants, such as GABAergic drugs, have shown more efficiency. Surgery may be required if lesions are noticed on the brain. Since the condition is associated with mental retardation and learning disabilities, occupational, speech, and physio-therapy are also required. The prognosis for children with ISSX is poor, despite treatment. Only about 12% of the affected patients progress to normal mental and motor development. Delay in treatment results in worse outcomes.

Molecular Genetics

The infantile spasms are considered to be due to abnormal interactions between the cortex and brainstem structures. It has also been suggested that an abnormal excessive secretion of ACTH by the immature brain, under the influence of various stressors, may be responsible for the spasms. Studies mapped the gene responsible for ISSX to the X chromosome, between the markers, DXS1226 and AHC. Two genes in this region, STK9 (Serine/Threonine Kinase 9) and ARX (Aristaless Related Homeobox) were found to be mutated in affected patients. Since both the genes are functionally distinct, one being a kinase, and the other a putative transcription factor, it is assumed that divergent mechanisms may lead to the clinical phenotype of ISSX.

Epidemiology in the Arab World

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Other Reports

Lebanon

Karam et al (2009) described two unrelated families with two children each affected with infantile spasm syndrome. Both sets of parents were consanguineous. ARX gene sequencing found no mutations. The authors still suspected an X-linked mode of inheritance, considering that all four patients were males. 

Oman

Koul et al. (2001) reported 44 children diagnosed with West syndrome over the period from 1993 to 2000.

Saudi Arabia

A study performed on 1000 Saudi patients by Al-Rajeh et al. (1990) reported that infantile spasms were seen in 3% of the cases studied. More specifically, 23% of the cases under the age of 1-year were diagnosed with West Syndrome.

United Arab Emirates

Sztriha et al. (1997) studied seven patients with symptomatic West syndrome several months after the onset of the spasms to understand diffuse and focal changes in glucose utilization and abnormal cerebral cortical perfusion in West syndrome. Significantly reduced perfusion was found in the bilateral anterior, mid frontal and perisylvian cortex, and in the left posterior frontal and temporal areas. Well localized, focal changes in the cortical perfusion were not found and the perfusion in the basal ganglia proved to be normal. Sztriha et al. (1997) suggested that these abnormalities in the cortical perfusion may reflect a pre-existing brain pathology together with an encephalopathy due to the hypsarrhythmia and infantile spasms.

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