COL4A1/COL4A2 mutations are rare genetic disorders with multisystem involvement and significant neurological involvement with continually evolving spectrum.

Six children being followed in epilepsy clinic with genetically proven COL4A1 mutations were reviewed.

The mean age was 6.2 years (Range 3 to 8.6 years) with equal numbers of males and females. Early infantile onset (3-6 months) seizures were the presenting symptom in 5/6 children. Epileptic spasm was the most common seizure type (6/6). One child with relatively late onset of seizure (2.5 years) was ambulatory, rest of the children were significantly delayed. Most of the children (5/6) had drug refractory epilepsy (DRE), 1/6 had epilepsy surgery and was seizure free. Visual impairment and optic atrophy were common ophthalmological findings. Porencephalic cyst and multiple punctate hemorrhage (4/6) were the most common neuroimaging findings, followed by schizencephaly, subdural hematoma, white matter signal changes. Rare (1/6) imaging findings were calcifications, dysplastic posterior fossa structures and decreased volume of basal ganglia and thalamus. Grossly abnormal EEGs were common to most children (5/6). One child had resolution of epileptiform discharges at the last follow up. All children had genetic diagnosis of COL4A1 mutation during infancy. One child unfortunately passed away, while 4/6 had significant disabilities.

Early onset seizures especially epileptic spasms suggest poor prognosis. Timely intervention with epilepsy surgery in selected candidates can improve the quality of life. Posterior fossa structures and basal ganglia can be involved rarely. Early genetic diagnosis alerts the clinician to anticipate poor seizure control and need for aggressive approach to management.

Sonali Singh
The Hospital for Sick Children
Canada

Ayako Ochi
The Hospital for Sick Children
Canada

Hiroshi Otsubo
The Hospital for Sick Children
Canada

Elizabeth Donner
The hospital for sick Children
Canada

George Ibrahim
The Hospital for Sick Children
Canada

Pradeep Krishnan
The Hospital for Sick Children
Canada

Elizabeth Pulcine
The Hospital for Sick children
Canada

Puneet Jain
The Hospital for Sick Children
Canada