The Phenotypic Spectrum of Tuberous Sclerosis Complex: A Canadian Cohort

Daad Alsowat; Robyn Whitney; Stacy Hewson; Puneet Jain; Valerie Chan; Nadia Kabir; Kimberly Amburgey; Damien Noone; Mathieu Lemaire; Blathnaid McCoy; Maria Zak

doi:10.1177/2329048X211012817

The Phenotypic Spectrum of Tuberous Sclerosis Complex: A Canadian Cohort

Child Neurol Open. 2021 May 4:8:2329048X211012817. doi: 10.1177/2329048X211012817. eCollection 2021 Jan-Dec.

Authors

Daad Alsowat¹, Robyn Whitney², Stacy Hewson³, Puneet Jain⁴, Valerie Chan⁴, Nadia Kabir⁴, Kimberly Amburgey³, Damien Noone⁵, Mathieu Lemaire⁵, Blathnaid McCoy⁴, Maria Zak⁴

Affiliations

¹ Epilepsy Program, Division of Pediatric Neurology, Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
² Epilepsy Program, Division of Neurology, Department of Pediatrics, McMaster Children's Hospital, Hamilton, Ontario, Canada.
³ Department of Genetic Counselling, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Epilepsy Program, Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁵ Division of Nephrology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.

Abstract

Objective: We aimed to further elucidate the phenotypic spectrum of Tuberous Sclerosis Complex (TSC) depending on genotype.

Methods: A retrospective review of patients seen in the TSC clinic at the Hospital for Sick Children was conducted and the frequency of TSC manifestations was compared based on genotype.

Results: Nineteen-patients had TSC1 mutations, 36 had TSC2 mutations and 11 had no mutation identified (NMI). Patients with TSC2 mutations had a higher frequency of early-onset epilepsy and more frequent systemic manifestations. The NMI group had milder neurologic and systemic manifestations. Our data did not demonstrate that intellectual disability and infantile spasms were more common in TSC2 mutations.

Conclusions: This is the first Canadian pediatric cohort exploring the genotype-phenotype relationship in TSC. We report that some manifestations are more frequent and severe in TSC2 mutations and that NMI may have a milder phenotype. Disease surveillance and counseling should continue regardless of genotype until this is better elucidated.

Keywords: genotype; no mutation identified (NMI); phenotype; surveillance; tuberous sclerosis complex (TSC).