Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations.

Only 17 participants were studied, and only 12 received full direct clinical and psychological assessment. There was no control group or randomised comparison, so differences from 22q13 deletions are descriptive and may reflect different ages, assessment methods, or samples. Loss of skills was reported by caregivers and was not measured with a standardized longitudinal instrument, so recall bias is possible. Cognitive tests reached floor for several young children, and some participants did not receive standardized IQ testing. Many participants were young, and only two of the 14 Seaver participants were post-pubertal, so seizures and psychiatric symptoms may be undercounted. Some participants had additional genetic or medical findings, such as a 17q12 microduplication in one individual, so SHANK3 may not explain every feature. Participants were referred through a syndrome foundation, research studies, and families, which may not represent all people with SHANK3 mutations.

Funded by the Beatrice and Samuel A. Seaver Foundation, Phelan-McDermid Syndrome Foundation, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and Robbins Foundation. The supplied text gives no author conflict-of-interest declaration.

Do not read the loss of skills in 11 of 17 people as evidence that a therapy caused or prevented it. This was a descriptive series of people with SHANK3 gene changes, with no treatment comparison and caregiver-reported skill loss.