Prader-Willi syndrome: Symptoms and topiramate response in light of genetics.

Autor:	Louveau C; Centre de Référence pour les Maladies Rares à expression Psychiatrique, GHU Paris Psychiatrie et Neurosciences, Paris, France., Turtuluci MC; Centre de Référence pour les Maladies Rares à expression Psychiatrique, GHU Paris Psychiatrie et Neurosciences, Paris, France., Consoli A; Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.; GRC-15, Dimensional Approach of Child and Adolescent Psychotic Episodes, Faculté de Médecine, Sorbonne Université, Paris, France., Poitou C; Nutrition Department, Rare Diseases Center of Reference 'Prader-Willi Syndrome and Obesity With Eating Disorders' (PRADORT), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, INSERM, Nutriomics, Sorbonne Université, Paris, France., Coupaye M; Nutrition Department, Rare Diseases Center of Reference 'Prader-Willi Syndrome and Obesity With Eating Disorders' (PRADORT), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, INSERM, Nutriomics, Sorbonne Université, Paris, France., Krebs MO; Centre de Référence pour les Maladies Rares à expression Psychiatrique, GHU Paris Psychiatrie et Neurosciences, Paris, France.; Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université Paris Cité, Paris, France., Chaumette B; Centre de Référence pour les Maladies Rares à expression Psychiatrique, GHU Paris Psychiatrie et Neurosciences, Paris, France.; Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université Paris Cité, Paris, France.; Department of Psychiatry, McGill University, Montréal, QC, Canada., Iftimovici A; Centre de Référence pour les Maladies Rares à expression Psychiatrique, GHU Paris Psychiatrie et Neurosciences, Paris, France.; Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université Paris Cité, Paris, France.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2023 Feb 06; Vol. 17, pp. 1126970. Date of Electronic Publication: 2023 Feb 06 (Print Publication: 2023).
DOI:	10.3389/fnins.2023.1126970
Abstrakt:	Introduction: Prader-Willi Syndrome (PWS) is a rare genetic condition, which affects one in 25,000 births and results in various phenotypes. It leads to a wide range of metabolic and endocrine disorders including growth delay, hypogonadism, narcolepsy, lack of satiety and compulsive eating, associated with mild to moderate cognitive impairment. Prognosis is especially determined by the complications of obesity (diabetes, cardiorespiratory diseases) and by severe behavioral disorders marked by impulsivity and compulsion. This heterogeneous clinical picture may lead to mis- or delayed diagnosis of comorbidities. Moreover, when diagnosis is made, treatment remains limited, with high interindividual differences in drug response. This may be due to the underlying genetic variability of the syndrome, which can involve several different genetic mutations, notably deletion or uniparental disomy (UPD) in a region of chromosome 15. Here, we propose to determine whether subjects with PWS differ for clinical phenotype and treatment response depending on the underlying genetic anomaly. Methods: We retrospectively included all 24 PWS patients who were referred to the Reference Center for Rare Psychiatric Disorders (GHU Paris Psychiatrie and Neurosciences) between November 2018 and July 2022, with either deletion ( N = 8) or disomy ( N = 16). The following socio-demographic and clinical characteristics were recorded: age, sex, psychiatric and non-psychiatric symptoms, the type of genetic defect, medication and treatment response to topiramate, which was evaluated in terms of eating compulsions and impulsive behaviors. We compared topiramate treatment doses and responses between PWS with deletion and those with disomy. Non-parametric tests were used with random permutations for p -value and bootstrap 95% confidence interval computations. Results: First, we found that disomy was associated with a more severe clinical phenotype than deletion. Second, we observed that topiramate was less effective and less tolerated in disomy, compared to deletion. Discussion: These results suggest that a pharmacogenomic-based approach may be relevant for the treatment of compulsions in PWS, thus highlighting the importance of personalized medicine for such complex heterogeneous disorders. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Louveau, Turtuluci, Consoli, Poitou, Coupaye, Krebs, Chaumette and Iftimovici.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu