Smith-Kingsmore Syndrome Foundation

Cycle 2

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Smith-Kingsmore Syndrome (SKS) is a rare, neurodevelopmental genetic disorder caused by changes (disease-causing variants) in the MTOR gene. SKS impacts the digestive, endocrine, metabolic and nervous systems. The most common symptoms in people with SKS are intellectual disability, developmental delay, large brain size (megalencephaly) and seizures.

Last updated 04/30/2026

Clinical

Disease Class

Developmental anomalies during embryogenesis

Epilepsy and seizure disorders

Genetic diseases

Intellectual disability and developmental syndromes

Multi-system genetic syndromes

Neurological diseases

Body Systems

Digestive

Endocrine

Metabolic

Nervous / Sensory

Organs

Brain

Known Genetic Link

Yes, one or more genes directly cause the condition

Causative Genes

MTOR

Contributory Genes

None specified / unknown

Type of Inheritance

Autosomal dominant

De novo

Newborn Screening

Disease Mechanism(s)

mTOR pathways dysregulation

Age of Onset

Prebirth

Average Age at Diagnosis

Early childhood (age 1+-5)

Middle childhood (6-11)

Life Expectancy

Adulthood (age 18-64)

Affected Sex(es)

Female

Intersex

Male

National Prevalence

51-100

Global Prevalence

101-1000

National Incidence

Less than 10

Global Incidence

Less than 10

Symptoms / Phenotypes

atypical puberty

autism

autistic behavior

developmental delay

distinctive facial features

excessive hunger / hyperphagia

gastrointestinal disorders

hyperactivity

intellectual disability

macrocephaly

seizures / epilepsy

sensory processing disorder / sensory hypersensitivity

sleep disorders

speech delay

Biomarkers

Diagnostic

· MTOR mutation (DNA testing or tissue testing for mosaic presentations), seizures, macrocephaly, sleep/wake dysfunction, intellectual disability, autism, epilepsy, developmental delays

Existing Therapies

Off-Label Drug Use

Regulatory Agency-Approved for Symptom Relief

· Seizure, ADHD, anxiety and sleep medication all used

Therapies in Development

Repurposed drug

· Rapamycin/Sirolimus - working on protocol design to assess possible therapeutic benefits; more extensive repurposed drug research currently underway

Therapeutic Development Stages

In research/exploratory phase

Therapeutic Development Role

Access to registry or natural history study

Data sharing

Funding

Organizational & Research

Cell Lines

None

Cell Lines, Institution

None

Cell Lines, share

N/A

Disease Model

Drosophila/fly

Mouse

Disease Model, Involvement

Consulted

Funded

Disease Model, share

Some of our disease models are freely available

Clinical Trial Role

Not involved

Biobank, Institution

COMBINEDBrain

Biobank, Involvement

Funded

Center of Excellence, Institution

None

Registry

Yes, we have a registry that we created

Data Collected, Registry

Clinical data

Electronic health records/electronic medical records

Genetic data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Patients

Platform, Registry

CoRDS

Natural History Study

Yes, we have collaborated on a natural history study

Data Collected, Natural History Study

Electronic health records/electronic medical records

Genetic data

Imaging data

Medication usage

Patient-reported outcomes

Prospective data

Retrospective data

Platform, Natural History Study

REDCap

FDA Patient Listening Session

FDA Patient-Focused Drug Development (PFDD) Program

ICD Codes

No, we do not have any ICD codes

Diagnostic Guidelines

Science Advisory Board Policies

Yes, willing to share SAB policies

Research Network Policies

Does not have a CRN

Patient Priority Survey

Research Roadmap

Yes we have a Research Roadmap, and will share policies

None

Europe