Disease Directory Phelan-McDermid Syndrome
Neurological

Phelan-McDermid Syndrome

Also known as: PMS, 22q13.3 deletion syndrome, SHANK3 haploinsufficiency

Prevalence

1-9 per 100,000 (Orphanet)

Onset

Neonatal, Infantile

Type

Genetic (chromosomal deletion or SHANK3 mutation, usually de novo)

Gene

SHANK3

About Phelan-McDermid Syndrome

Phelan-McDermid syndrome is caused by deletion of 22q13.3 or point mutations in SHANK3, encoding a scaffolding protein at glutamatergic synapses critical for synapse formation and plasticity. Clinical features include severe intellectual disability, absent or severely delayed speech, global developmental delay, neonatal hypotonia, autism spectrum features, minor dysmorphic features, and absent or minimal pain perception. Insulin-like growth factor 1 (IGF-1) and intranasal insulin have been studied as potential treatments.

Common Clinical Features

Absent or severely limited speech Severe intellectual disability Autism spectrum features Neonatal hypotonia Absent pain response Seizures (50%) Minor dysmorphic features

Clinical Trial Eligibility Tips

What to know before applying to Phelan-McDermid Syndrome trials.

22q13.3 deletion size or specific SHANK3 variant must be documented — deletion size correlates with phenotype severity and affects trial eligibility

Autism diagnostic measures (ADOS-2, ADI-R) are standard baseline tools alongside adaptive behavior scales

IGF-1 and insulin trials require baseline metabolic and IGF-1 level documentation

Regression episodes (loss of previously acquired skills, often with fever) should be tracked and documented — regression history affects eligibility

Patient Resources

Patient Organization

Phelan-McDermid Syndrome Foundation

Visit website ↗

Natural History Registry

PMS Foundation International Registry

Join registry ↗

Orphanet

European reference resource for rare diseases (ORPHA:48652)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Phelan-McDermid Syndrome trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Phelan-McDermid Syndrome. Updated daily.

Related Rare Diseases