COL4A1 Gene Mutation Masquerading as Cerebral Palsy: Report of a Rare Case
Shiji Chalipat1, Jeevana Bollineni2, Priyanka Shah2
1Pediatric Neurology, Dr. D Y Patil Medical College, Hospital and Research Centre, Dr. D Y Patil Vidyapeeth (Deemed to be University), Pune, IND.
Insights
Mutations in the Collagen Type 4 alpha 1 (COL4A1) gene can cause significant neurological issues, including developmental delay and epilepsy. Early suspicion in children with spastic quadriplegia is crucial for timely diagnosis and management.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Collagen Type 4 alpha 1 (COL4A1) is vital for vascular basement membranes.
- Pathogenic mutations in COL4A1 lead to diverse clinical presentations.
- Cerebral Palsy (CP) shares symptoms with COL4A1 mutations, complicating diagnosis.
Observation:
- A two-and-a-half-year-old boy presented with global developmental delay and epileptic spasms.
- Clinical examination revealed microcephaly, nystagmus, and limb spasticity.
- Brain imaging showed white matter changes, bleeds, cysts, and calcifications.
Findings:
- Molecular genetic testing identified a heterozygous COL4A1 gene mutation (p.Gly1050Ala) with autosomal dominant inheritance.
- The patient developed drug-refractory epilepsy requiring complex management.
- COL4A1 mutations can closely mimic symptoms of Cerebral Palsy.
Implications:
- Prompt diagnosis of COL4A1 mutations is essential in children with spastic quadriplegia.
- High index of suspicion for COL4A1 gene mutations is recommended.
- Timely intervention can potentially improve neurological outcomes in affected individuals.
Abstract:
The Collagen Type 4 alpha 1 (COL4A1), is an important component of nearly all vascular basement membranes. Pathogenic mutation of this gene results in varied manifestations. In this report, we describe a two-and-a-half-year-old boy with an eventful perinatal period, global developmental delay, and epileptic spasms. Examination revealed microcephaly, nystagmus, and spasticity in limbs. Electroencephalogram showed multifocal epileptiform discharges and MRI brain demonstrated periventricular white matter changes, intracerebral bleeds, and porencephalic cysts. CT brain showed intracranial calcifications and screening for congenital infection was negative. The molecular genetic evaluation was later confirmed with a heterozygous mutation of the COL4A1 gene on exon 37 (variant - p.Gly1050Ala) with an autosomal dominant inheritance pattern. Currently, the child has developed drug-refractory epilepsy requiring polypharmacy and the ketogenic diet. COL4A1 gene mutations are close mimickers of Cerebral Palsy, hence a high index of suspicion should be exercised while approaching a child with spastic quadriplegia in order to promptly diagnose and manage such children for a better neurological outcome.
