Epileptic Encephalopathy, Early Infantile, 2

Alternative Names

  • EIEE2
  • Infantile Spasm Syndrome, X-Linked 2
  • ISSX2
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WHO-ICD-10 version:2010

Diseases of the nervous system

Episodic and paroxysmal disorders

OMIM Number

300672

Mode of Inheritance

X-linked dominant

Gene Map Locus

Xp22.13

Description

Epileptic Encephalopathy, Early Infantile, 2 is a severe neurological disorder characterized by infantile-onset seizures, global developmental delay, psychomotor regression, microcephaly, mental retardation, motor dyspraxia, hypotonia and myoclonus.  Most patients are wheelchair bound and skeletal anomalies include scoliosis, small feet, and small hands with tapering fingers.  Patients exhibit subtle facial dysmorphia such as a broad, prominent forehead, deep-set, large-appearing eyes with well-defined eyebrows, anteverted nares, and full lips.  Affected individuals may also exhibit behavioral patterns such as hand wringing, washing, breath-holding, and autistic tendencies.  Other symptoms include hyperventilation, constipation, gastroesophageal reflux, sleep difficulties, and autonomic disturbances.  Due to phenotypic overlap, the disorder was earlier speculated to be a subset of Rett syndrome, but is now considered a distinct entity.  It has been found to occur in women more often than men, with a ratio of 5:1.

Diagnosis of EIEE2 can be done by electroencephalogram studies to identify atypical hypsarrhythmia patterns.  While there is no cure for the disorder, treatment is focused on improving symptoms and providing a better quality of life.  Patients may require anticonvulsants to control seizures along with steroid treatment and a ketogenic diet.  Vagal nerve stimulation may also be beneficial.  Affected individuals also require physical therapy, occupational therapy, and speech and augmentative communication therapy.

Molecular Genetics

The disorder follows an X-linked dominant pattern of inheritance and is caused by mutations in the CDKL5 gene.  As males have only one X chromosome, they are more severely affected by the disorder and most may not survive till birth.  Hence females are more commonly diagnosed with the condition.  The severity of the disorder in females is dependent on X-inactivation, as it may result in the inactivation of the healthy CDKL5 gene.

The CDKL5 gene encodes a serine/threonine kinase enzyme believed to play a role in neuron migration, dendrite morphogenesis and axon extension.  Variants associated with the disorder include missense mutations, splice site mutations, deletions and insertions that either alter the function of the CDKL5 protein or result in its absence.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
300672.1United Arab EmiratesUnknownNo Global developmental delay; Development...NM_001323289.2:c.593G>AHeterozygousAl-Shamsi et al. 2016 De novo mutation in ...
300672.2United Arab EmiratesFemaleNoNo Epileptic encephalopathy; Global develop...NM_003159.3:c.229_232delHeterozygousSaleh et al. 2021 de novo mutation
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