Japanese siblings with neuronal ceroid lipofuscinosis type 7 showing different initial symptoms due to biallelic MFSD8 variants: A case report

Neuronal ceroid lipofuscinosis type 7 (CLN7) is caused by variants in the major facilitator superfamily domain-containing protein 8 ( MFSD8 ) gene. Research on gene therapy for CLN7 is currently ongoing, highlighting the importance of early diagnosis. There are very few detailed case reports on the clinical course of this disease. This report presents the case of Japanese siblings with CLN7, whose definitive diagnosis was achieved through genetic testing. Patient 1, a 20-year-old boy (elder brother), was diagnosed with psychomotor retardation and suspected autism spectrum disorder. He developed myoclonus and epilepsy, with brain magnetic resonance imaging (MRI) revealing cerebellar atrophy at 4.5 years of age. Seizures progressed refractorily. At age 9, he had difficulty walking, and became bedridden a year later. Patient 2, a 15-year-old boy (younger brother), began falling frequently at age 4, and developed epilepsy with visual acuity reduction at age 5. Brain MRI revealed cerebellar atrophy. The seizures progressed refractorily, and myoclonus was observed at the age of 8 years. He became bedridden shortly after. Exome sequencing identified compound heterozygous variants of MFSD8, NM_152778.2:c.599G>A, p.(Trp200*) and c.706C>A, p.(Arg236Ser) leading to the diagnosis of CLN7. In this case, a definitive diagnosis was established through genetic testing, as enzyme activity assessment and skin biopsy results were inconclusive. The diversity of the initial symptoms and the low awareness due to the rarity of the disease contributed to diagnostic delays. The accumulation of case reports is necessary, and genetic testing is highly valuable for early diagnosis.