Children with genetically confirmed Hereditary Spastic Paraplegia (HSP): A case series from Eastern Mediterranean Region of Turkey

Objectives New genes and associated hereditary spastic paraplegia (HSP) subtypes continue to be identified in recent years.The inheritance patterns of the cases are defined as autosomal dominant (AD),autosomal recessive (AR), X-linked dominant or mitochondrial inheritance. In this case series, we aimed to expand the genotype-phenotype correlation of the disease in cases of childhood-onset HSP. Methods We retrospectively evaluated 4 consecutive children with genetically confirmed HSP at the pediatric neurology division of Baskent University, Adana Hospital between february 2019 and June 2022. Results Four patients with genetically confirmed diagnosis were included. The age of onset of symptoms ranged from 6 months to 7 years and 3 patients were less than 2 years old at the time of onset. The follow-up period of the patients was 4-9 years.All of the patients admitted with lower extremity spasticity,weakness,brisk reflexes and psychomotor retardation.One patient each had seizure, ataxia and two of them had neurogenic bladder. Genetic analyzes were revealed pathogenic mutations as homozygous C19orf12 c.385 (AR spastic paraplegia 43),heterozygous KIF1A c.773 C>T (AD Spastic Paraplegia 30), heterozygous SPG11 c.6730 C>T (AR Spastic Paraplegia 11) and a de novo pathogenic heterozygous GBA2 c.1688-2A>c (AR spastic paraplegia 46),respectively. Conclusion Although C19orf12 homozygous mutations are often characterized by NIBA, it may cause HSP less frequently. Herein, we report the second case of heterozygous SPG11 mutation related HSP and second Turkish patient with KIF1A mutation in literature.In addition,heterozygous mutation with GBA2-associated HSP are reported for the first time and expand the clinical spectrum of the syndrome.
Keywords: hereditary, spastic, paraplegia, c19orf12,kıf1a,spg11,gba2