Clinical case: Phelan–McDermid and pharmacological management

Ballesteros, Alejandro; Rosero, Á.S.; Inchausti, Félix; Manrique, Edna Joana Cláudio; Sáiz, H.; Carlos, Carolina Dias; María, Z.

doi:10.1016/j.eurpsy.2017.01.410

Cited by 3 publications

(1 citation statement)

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“…Treatment of a patient with lithium for one year showed decreased autism severity [44]. Other reports include case studies of individual patients (treatment of a 70-year-old woman with a 610 kb deletion [45] and a 13-year-old girl with a SHANK3 microdeletion [46]. A recent case series for the treatment of PMS with lithium was reported in 2015 by researchers Serret and colleagues [47].…”

Section: Lithiummentioning

confidence: 99%

Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome

Dyar

Meaddough

Sarasua

et al. 2021

Genes

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Phelan-McDermid syndrome (PMS) is a genetic disorder often characterized by autism or autistic-like behavior. Most cases are associated with haploinsufficiency of the SHANK3 gene resulting from deletion of the gene at 22q13.3 or from a pathogenic variant in the gene. Treatment of PMS often targets SHANK3, yet deletion size varies from < 50kb to > 9Mb, potentially encompassing dozens of genes and disrupting regulatory elements altering gene expression, inferring the potential for multiple therapeutic targets. Repurposed drugs have been used in clinical trials investigating therapies for PMS: insulin-like growth factor 1 (IGF-1) for its effect on social and aberrant behaviors, intranasal insulin for improvements in cognitive and social ability, and lithium for reversing regression and stabilizing behavior. The pharmacogenomics of PMS is complicated by the CYP2D6 enzyme which metabolizes antidepressants and antipsychotics often used for treatment. The gene coding for CYP2D6 maps to 22q13.2 and is lost in individuals with deletions larger than 8Mb. Because PMS has diverse neurological and medical symptoms, many concurrent medications may be prescribed, increasing the risk for adverse drug reactions. At present, there is no single best treatment for PMS. Approaches to therapy are necessarily complex and must target variable behavioral and physical symptoms of PMS.

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Section: Lithiummentioning

confidence: 99%

Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome

Dyar

Meaddough

Sarasua

et al. 2021

Genes

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Opportunities for ABA intervention in Phelan–McDermid syndrome

Schroeder

Witts

Traub

2021

International Journal of Developmental Disabilities

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Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature

et al. 2019

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Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene 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 in SHANK3 exhibiting neuropsychiatric decompensation and loss of skills demonstrate that loss of one copy of SHANK3 is 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 the ARSA gene 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.

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Clinical case: Phelan–McDermid and pharmacological management

Cited by 3 publications

References 0 publications

Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome

Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome

Opportunities for ABA intervention in Phelan–McDermid syndrome

Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature

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