A Paula Grigorian

BASICS

DESCRIPTION

• Genetic neurodevelopmental disorder characterized by the triad of:

– Infantile spasm type seizure disorder

– Agenesis of corpus callosum

– Chorioretinal lacunae

EPIDEMIOLOGY

Incidence

Unknown but very rare

Prevalence

Kroner (1) estimated there to be greater than 853 cases in the US and several thousand cases worldwide.

RISK FACTORS

None known, genetic disorder

Genetics

• Presumed X-linked dominant disorder

• Lethal in males, affected surviving males rare and usually have chromosomal aberration of sex chromosomes (e.g., translocation, XXY)

• No gene definitively identified

• Phenocopy del1p36

(NOTE: Not to be confused with Aicardi-Goutières syndrome)

GENERAL PREVENTION

• Unknown, prenatal genetic testing not available

• Prenatal ultrasound can detect corpus callosum abnormalities

PATHOPHYSIOLOGY

Developmental defect presumably of neuroectoderm

ETIOLOGY

Presumed gene mutation

COMMONLY ASSOCIATED CONDITIONS

• Ocular associations

– Cardinal feature: Chorioretinal lacunae (see below)

– Congenital optic disc anomalies: Coloboma, hypoplasia, congenital pigmentation

– Microphthalmia, retinal detachment, nystagmus

• Systemic associations

– Vertebral malformations: Fused vertebrae, scoliosis, spina bifida, costal malformations (absent ribs, fused or bifurcated ribs)

– Muscular hypotonia, microcephaly, dysmorphic facies, auricular anomalies

– Brain anomalies: Dysgenesis of the corpus callosum (complete or partial), cerebral asymmetry with polymicrogyria or pachygyria, periventricular and intracortical gray matter heterotopias, midline arachnoid cysts, choroid plexus papillomas, and ventriculomegaly and intracerebral cysts, often at the third ventricle and in the choroid plexus. Severe mental retardation

– Gastrointestinal: Constipation, diarrhea, gastroesophageal reflux, difficulty feeding

– Integument: Vascular and pigmented lesions

DIAGNOSIS

HISTORY

Infants 3–5 months of age may present with: Decreased visual acuity, amblyopia, or strabismus, but more often present with neurological manifestations of developmental delay, hypotony, and intractable seizures

PHYSICAL EXAM

• Classic triad

– infantile spasms

– agenesis of corpus callosum

– chorioretinal lacunae

• Major features

– Cortical malformations (mostly polymicrogyria)

– Periventricular and subcortical heterotopias

– Cysts around third cerebral ventricle and/or choroid plexus

– Optic disc/nerve coloboma or hypoplasia

• Supporting features

– Vertebral and rib abnormalities

– Microphthalmia

– “Split-brain” EEG, infantile spasm hypsarrhythmia

– Cerebral hemispheric asymmetry

– Vascular malformations or vascular malignancy

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