8 years from symptoms to genetic diagnosis
A review of 16 childhood-onset cases of HSP from two clinics in Atlanta Georgia (USA) found the time from symptom onset to genetic confirmation was 8 years on average. 70% of cases were complicated by one or more of cognitive impairment, polyneuropathy, developmental delay, autism, epilepsy and ADHD.
Background: Hereditary spastic paraplegia (HSP) encompasses several rare genetic disorders characterized by progressive lower extremity spasticity and weakness caused by corticospinal tract degeneration. Published literature on genetically confirmed pediatric HSP cases is limited.
Methods: We conducted a retrospective review of childhood-onset HSP cases followed in the neuromuscular clinics at Children’s and Emory Healthcare in Atlanta. Clinical presentation, family history, examination, electrodiagnostic data, neuroimaging, genetic test results, comorbidities, and treatment were recorded.
Results: Sixteen patients with HSP (eight males, eight females) with a mean age 19 years ± 15.7 years were included. Ten patients (66%) presented with gait difficulty. Seven (44%) were ambulatory at the last clinic follow-up visit with an average disease duration of 7.4 years. Genetically confirmed etiologies included SPAST (3 patients), MARS (2), KIF1A (2), KIF5A (1), SACS (1), SPG7 (1), REEP1 (1), PNPT1 (1), MT-ATP6 (1), and ATL1 (1). Symptom onset to genetic confirmation on an average was 8.2 years. Sensory motor axonal polyneuropathy was found in seven patients, and two exhibited cerebellar atrophy on magnetic resonance imaging (MRI) of the brain. Neurological comorbidities included developmental delay (n = 9), autism (n = 5), epilepsy (n = 3), and attention-deficit/hyperactivity disorder (n = 2).
Conclusions: In our study, a significant proportion (70%) of subjects with childhood-onset HSP had comorbid neurocognitive deficits, polyneuropathy with or without neuroimaging abnormalities, and rare genetic etiology. Genetic diagnosis was established either through inherited genetic neuropathy panel or whole-exome sequencing, which supports the utility of whole-exome sequencing in aiding in HSP diagnosis.
SOURCE: Pediatr Neurol. 2022 May;130:7-13. doi: 10.1016/j.pediatrneurol.2022.02.007. Epub 2022 Mar 3. PMID: 35303589 Copyright © 2022.
Childhood-Onset Hereditary Spastic Paraplegia (HSP): A Case Series and Review of Literature
1. Florida Atlantic University, Charles E. Schmidt College of Medicine, Boca Raton, Florida.
2. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia.
3. Department of Pediatrics, Genetics Section, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Little Rock, Arkansas.
4. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia; Division of Pediatric Neurology, Children’s Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia.