BNS Epilepsy, Global Developmental Delay, Optic Coloboma, and Vesicoureteral Reflux as Leading Symptoms of COL4A1 Mutation: A Case Report

Background: Heterozygous mutations of COL4A1 gene lead to aut.-dom. handed diseases with variable clinical spectrum. Due to connective tissue disruption different organic systems are involved. A complex of symptoms including developmental disorders, cerebral, ocular and renal malformations, seizures as well as perinatal intracranial hemorrhage of unknown origin in term newborns could indicate COL4A1-associated diseases. In addition, autosomal dominant familiar porencephalia and hereditary angiopathy with nephropathy, aneurysm und muscle cramps (HANAC syndrome) belong to the spectrum of these mutations. Here, we report signs and clinical course of a novel COL4A1 deletion in an infant.

Case Report: An 8-month-old male infant presented for diagnostics and therapy of BNS seizures. Pregnancy and birth have been complicated by polyhydramnion and vesicoureteral reflux. Clinically, general muscular hypotonia, macroglossia, optic coloboma were present. Diagnostics: Electroencephalography confirmed hypsarrhythmia. The cMRI showed a nonspecific delay of myelination. There were no signs of metabolic etiology. BNS epilepsy was treated successfully with steroids. However, global developmental disorder persisted. Due to hydronephrosis vesical fistula was installed. The complex of symptoms led to the differential diagnosis of connective tissue disease, thus microarray analysis was performed verifying the deletion 13q34 at the age of 19 months. In this specified area the COL4A1 gene is located. The copy number changes of the chromosomal region of the patient have not been published yet.

Conclusion: Combined symptoms of cerebral, ocular and renal abnormalities, opticus coloboma, developmental disorder and epilepsy may indicate COL4A1 mutations which should be included in the possible differential diagnosis in view of the risk for cerebral bleeding.