Children with Genetically Confirmed Hereditary Spastic Paraplegia: A Single-Center Experience
Abstract
Highlights
- We identified a new inheritance pattern, a novel variants and a different clinical phenotype in some forms of hereditary spastic paraplegia.
- The new inheritance patterns, new variants and phenotypes identified will contribute to the clinical and genetic diagnosis and monitoring of HSP.
Abstract
1. Introduction
2. Materials and Methods
- DNA Sequencing
- Variant Analysis and Classification
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Patient No/ Sex | Clinical Follow-Up Ages | Family Medical History/ Consanguinity | Physical and Neurological Findings | Diagnosis | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Age (y/m) | Presentation Age | Time of Progression of Symptoms | Follow Up Time | Age at Time of Diagnosis | Presentation Symptoms | Early Motor Development | Neurologic Findings | Initial | Final | ||
1/F | 7 y 6 m | 2y | 5 y | 5 y 6 m | 6 y 1 m | No/No | Gait disturbance and urine, stool incontinence | Able to walk at the age of 2 | Spastic gait, brisk reflexes | HSP | SPG 11 P-HSP |
2/M | 4 y 7 m | 6 m | 2 y 3 m | 4 y 1 m | 2 y | No/Yes | Motor delay | No gain of ability to walk | Spastic gait, brisk reflexes, intellectual disability | DD | SPG46 C-HSP |
3/F | 9 y 10 m | 1y | Stable disease | 8 y 10 m | 7 y | Yes/No | Gait disturbance | Able to walk at the age of 18 m | Spastic gait and brisk reflexes | HSP | SPG30 P-HSP |
4/F | 16 y 11 m | 7y | 7 y | 9 y 11 m | 14 y 2 m | Yes/Yes | Generalized weakness, falling frequently, and urine incontinence | No delayed motor milestones | Spastic gait, brisk reflexes, ataxia, ID, weakness in lower limbs | ID | SPG43 C-HSP |
5/M | 5 y 6 m | 2 y 6 m | 2 y 6 m | 3 y | 3 y | Yes/No | Gait disturbance and pain in lower limbs | No delayed motor milestones | Brisk reflexes, lower limb weakness | Spinal cord injury | SPG73 P- HSP |
6/F | 5 y 8 m | 2 y 6 m | 2 y 6 m | 3 y 2 m | 4 y 1 m | Yes/Yes | Tiptoe walking | No delayed motor milestones | Lower limb weakness, brisk reflexes, spasticity | HSP | SPG57 P-HSP |
7/F | 7 y 2 m | 1 y | Stable disease | 2 y 8 m | 7 y | Yes/No | Delayed gait, Falling frequently | Able to walk at the age of 4, 5 | Lower limb weakness, spasticity, Delayed speech, ID | CP | SPG4 P-HSP |
8/F | 6 y 3 m | Birth | Stable disease | 4 y 3 m | 5 y 5 m | Yes/No | Seizures, gait disturbance | No gain of ability to walk | Mild dysmorphic features, Spastic gait, brisk reflexes | Epilepsy, ID | SİNO syndrome C-HSP |
9/F | 12 y 9 m | 12 y | 12 y | 8 m | 12 y 1 m | Yes/No | Gait disturbance, falling frequently | No delayed motor milestones | Lower limb weakness, brisk reflexes, spasticity | HSP | SPG83 P-HSP |
10/F | 12 y 3 m | 1 y 6 m | 10 y | 1 y 4 m | 12 y 3 m | Yes/No | Gait disturbance, ID | Able to walk at the age of 2 | Failure to thrive, mild dysmorphic features, lower limb weakness, spasticity | MD | SPG5 C-HSP |
Patient No | Neurologic Diagnostic Tests | Neuroimaging Tests | Genetic Findings | Treatment | |||
---|---|---|---|---|---|---|---|
Metabolic Screening Tests | ENMG | EEG | Brain MRG | Spinal MRG | |||
1 | - | - | - | Cerebellar hypoplasia, vermis dysplasia and corpus callosum (CC) hypoplasia | Normal | SPG11 c.6730C>T heterozygote (p.L2244F) | Physical therapy |
2 | Normal | Normal | Centrotemporal spike and waves on the left side with normal background | CC hypoplasia | Normal | GBA2 NM_020944.3 c.1688-2A>C heterozygote | Physical therapy, baclofen, diazepam, orthopedic braces, levetiracetam |
3 | Normal | - | Normal | Vermis and CC hypoplasia | Normal | KIF1A c.773C>T heterozygote (p.V391M) | Physical therapy, baclofen |
4 | Normal | Normal | Normal | Bilateral globus pallidus T2 hypointensity and iron accumulation | - | C19orf12c.385C>T (p.Q1239*)(p.Gln129Ter) Homozygote | Physical therapy, carbidopa/levodopa, baclofen, |
5 | - | - | - | Normal | Normal | CPT1C c.109C>T (p.R37C) heterozygote | Physical therapy |
6 | Normal | - | - | Normal | Normal | TFG NM_001195478.1 c.269-8_269-4dup Homozygote TFG NM_001195478.1 c.288_297 delCCTTGAATCAinsTGACTTG Homozygote | Physical therapy, baclofen, orthopedic braces |
7 | Normal | Normal | Normal | Normal | Normal | SPAST NM_014946.4 c.1496G>A heterozygote p.R499H | Physical therapy, baclofen orthopedic braces |
8 | Normal | - | Multifocal spike and waves pattern | Vermian, CC and brainstem hypoplasia | Normal | KIDINS220 NM_020738.4 c.4388C>A heterozygote p.S1463* | Physical therapy, clonazepam, sodium valproate |
9 | Normal | Normal | Normal | Normal | Normal | HPDL NM_032756.4 c.149G>A (p.Gly50Asp) Homozygote | Physical therapy, carbidopa/levodopa, baclofen, CoQ10, vitamin B1, B2 and biotin |
10 | Normal | Normal | Normal | Normal | Normal | CYP7B1 NM_004820.5 c.1346G>A Homozygotep.C449y | Physical therapy, ursodeoxycholic acid (UDCA), orthopedic braces |
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Besen, S.; Özkale, Y.; Özkale, M.; Bozdoğan, S.T.; Alkan, Ö.; Ceylaner, S.; Erol, İ. Children with Genetically Confirmed Hereditary Spastic Paraplegia: A Single-Center Experience. Children 2025, 12, 1332. https://doi.org/10.3390/children12101332
Besen S, Özkale Y, Özkale M, Bozdoğan ST, Alkan Ö, Ceylaner S, Erol İ. Children with Genetically Confirmed Hereditary Spastic Paraplegia: A Single-Center Experience. Children. 2025; 12(10):1332. https://doi.org/10.3390/children12101332
Chicago/Turabian StyleBesen, Seyda, Yasemin Özkale, Murat Özkale, Sevcan Tuğ Bozdoğan, Özlem Alkan, Serdar Ceylaner, and İlknur Erol. 2025. "Children with Genetically Confirmed Hereditary Spastic Paraplegia: A Single-Center Experience" Children 12, no. 10: 1332. https://doi.org/10.3390/children12101332
APA StyleBesen, S., Özkale, Y., Özkale, M., Bozdoğan, S. T., Alkan, Ö., Ceylaner, S., & Erol, İ. (2025). Children with Genetically Confirmed Hereditary Spastic Paraplegia: A Single-Center Experience. Children, 12(10), 1332. https://doi.org/10.3390/children12101332