Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature
Bibliographic record
Abstract
Abstract Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of theSHANK3gene on chromosome 22q13.33 and is characterized by intellectual disability, hypotonia, severe speech impairments, and autism spectrum disorder. Emerging evidence indicates that there are changes over time in the phenotype observed in individuals with PMS, including severe neuropsychiatric symptoms and loss of skills occurring in adolescence and adulthood. To gain further insight into these phenomena and to better understand the long-term course of the disorder, we conducted a systematic literature review and identified 56 PMS cases showing signs of behavioral and neurologic decompensation in adolescence or adulthood (30 females, 25 males, 1 gender unknown). Clinical presentations included features of bipolar disorder, catatonia, psychosis, and loss of skills, occurring at a mean age of 20 years. There were no apparent sex differences in the rates of these disorders except for catatonia, which appeared to be more frequent in females (13 females, 3 males). Reports of individuals with point mutations inSHANK3exhibiting neuropsychiatric decompensation and loss of skills demonstrate that loss of one copy ofSHANK3is sufficient to cause these manifestations. In the majority of cases, no apparent cause could be identified; in others, symptoms appeared after acute events, such as infections, prolonged or particularly intense seizures, or changes in the individual’s environment. Several individuals had a progressive neurological deterioration, including one with juvenile onset metachromatic leukodystrophy, a severe demyelinating disorder caused by recessive mutations in theARSAgene in 22q13.33. These reports provide insights into treatment options that have proven helpful in some cases, and are reviewed herein. Our survey highlights how little is currently known about neuropsychiatric presentations and loss of skills in PMS and underscores the importance of studying the natural history in individuals with PMS, including both cross-sectional and long-term longitudinal analyses. Clearer delineation of these neuropsychiatric symptoms will contribute to their recognition and prompt management and will also help uncover the underlying biological mechanisms, potentially leading to improved interventions.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.012 | 0.011 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".