Cerebral small vessel disease caused by PLOD3 mutation: Expanding the phenotypic spectrum of lysyl hydroxylase-3 deficiency.

Introduction: Pathogenic variants in PLOD3, encoding lysyl hydroxylase-3 (LH3), can cause a hereditary connective tissue disorder that has rarely been reported. It is a multi-system disease, presenting with craniofacial dysmorphisms, skeletal and eye manifestations, sensorineural hearing loss, and variable skin manifestations. Severe central nervous system involvement has not been reported.

Case presentation: A 10-month-old girl was admitted with development delay and clustered epileptic spasms. Hypertelorism, an upturned nose, and low-set ears were noted in physical examination. Cerebral magnetic resonance imaging showed multiple intracranial malacias and bleeding foci, extensive abnormal signals in the white matter, and obvious brain atrophy, which was consistent with cerebral small vessel disease (SVD). Electroencephalography suggested hypsarrhythmia. The vertebrae were flattened. The distal end of the metacarpal bone in the left hand was irregular. She was diagnosed with West syndrome. Whole-exome sequencing revealed a novel homozygous variant of c.1216_1218delCTC (p.L406del) in PLOD3, which was found to be inherited from her heterozygous parents.

Conclusion: We report a patient with pathogenic PLOD3 mutation who presented with cerebral SVD. This report expands the phenotypic spectrum of LH3 deficiency.