Psychiatric Phenotype Characterization of Individuals With FOXP1 Syndrome

Recruiting

• Conditions: FOXP1 Syndrome
• Interventions: Other: Semi-structured interviews; Other: Heteroquestionnaires

• Registration Number: NCT06211673
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

FOXP1 syndrome is a rare genetic disorder with a variable phenotype, characterized somatically by facial dysmorphia, dysphagia, hypotonia, relative or real macrocephaly, which may be associated with cerebral, cardiac, urogenital and ocular malformations. Psychiatrically, the syndrome manifests as a global developmental delay, then as mild to severe intellectual development disorder, speech and language impairments, behavioral issues that may include autistic features, hyperactivity and emotional lability. Assessing a cohort of 17 patients with FOXP1 syndrome, Trelles et al (2021) reported a significant frequency of autistic spectrum disorders, attention deficit/hyperactivity disorder (ADHD), and anxiety disorders. They also noted the presence of repetitive behaviors in the majority of patients and sensory-seeking behaviors. However, within the patient population at the Child and Adolescent Psychiatry Department of Necker Enfants Malades Hospital, a significant prevalence of psychotic disorders was observed. Additionally, families reported ineffectiveness and poor tolerance of methylphenidate in these patients. Therefore, it appears crucial to further characterize the psychiatric phenotype of individuals with FOXP1 syndrome and explore the link between agitation and psychotic prodromes.

Detailed Description

FOXP1 syndrome is a rare genetic pathology disorder with a variable phenotype, characterized somatically by facial dysmorphia, dysphagia, hypotonia, relative to or real macrocephaly, which may be associated with cerebral, cardiac, urogenital and ocular malformations. Psychiatrically, the syndrome manifests as a global developmental delay, then as mild to severe intellectual development disorder, speech and language impairments, behavioral abnormalities issues that may include autistic features, hyperactivity and emotional lability. Nevertheless, the investigative team of the study noted within the population of patients with FOXP1 syndrome followed in the child and adolescent psychiatry department of the Necker Enfants Malades hospital a significant prevalence of psychotic disorders. Furthermore, families report a lack of effectiveness and poor tolerance of methylphenidate in these patients. Also, it seems important to continue the characterization of the psychiatric phenotype of patients with FOXP1 syndrome and to question the link between agitation and psychotic prodromes. Assessing a cohort of 17 patients with FOXP1 syndrome, Trelles et al (2021) reported a significant frequency of autistic spectrum disorders, attention deficit/hyperactivity disorder (ADHD), and anxiety disorders. They also noted the presence of repetitive behaviors in the majority of patients and sensory-seeking behaviors. However, within the patient population at the Child and Adolescent Psychiatry Department of Necker Enfants Malades Hospital, a significant prevalence of psychotic disorders was observed. Additionally, families reported ineffectiveness and poor tolerance of methylphenidate in these patients. Therefore, it appears crucial to further characterize the psychiatric phenotype of individuals with FOXP1 syndrome and explore the link between agitation and psychotic prodromes.

The different elements that will be assessed include:

* hyperactivity symptoms;

* attention disorder symptoms;

* psychotic symptoms;

* autistic symptoms;

* sensory peculiarities;

* anxiety symptoms;

* sleeping disturbances;

* behavioral issues;

* general psychopathology;

* adaptive skills. Furthermore, the study will seek to determine whether agitation falls within the scope ofADHD (Attention Deficit Disorder with/without Hyperactivity) or whether if it is part of a context of emerging psychotic symptomatology.

Study Timeline

• Status Verified: 2024-01
• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-09
• Study First Posted: 2024-01-18
• Study Start: 2024-01-19
• Last Update Submitted: 2024-01-31
• Last Update Posted: 2024-02-01
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Minor or adult patient, without age limit, presenting with FOXP1 syndrome due to an identified genetic anomaly affecting the FOXP1 gene;
• Patient who has sought consultationat Necker-Enfants Malades hospital;
• Legal guardians of the minor patient or legal representative of the adult patient, and the minor or adult patient capable of providing consent to participate in the study, informed about the study and not objecting to participation in the study.

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Exclusion Criteria

• Non French-speaking legal guardians or legal representatives of the patient;
• Illiterate legal guardians or legal representatives of the patient.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients and legal representatives	Semi-structured interviews	Minors and adults, without age limit, presenting with FOXP1 syndrome due to a genetic anomaly affecting the FOXP1 gene that has been identified, who have sought consultation at Necker-Enfants Malades Hospital, with at least one of the legal guardians or the legal representative being francophone.
Patients and legal representatives	Heteroquestionnaires	Minors and adults, without age limit, presenting with FOXP1 syndrome due to a genetic anomaly affecting the FOXP1 gene that has been identified, who have sought consultation at Necker-Enfants Malades Hospital, with at least one of the legal guardians or the legal representative being francophone.

Primary Outcome Measures

Name	Time	Method
Attention deficit/hyperactivity symptoms	Day 0 and 21	Attention deficit/hyperactivity symptoms measured by the Conners 3 scale and the Scale of Attention in Intellectual Disability - Parent version (SAID-P).; Conners 3 scale: Scale for evaluating symptoms of Attention Deficit Hyperactivity Disorder (ADHD), Conduct Disorder, and Oppositional Defiant Disorder in individuals aged 6 to 18 years.; SAID-P: Scale for assessing symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in children with intellectual development disorders. The scale is currently undergoing validation.
Sleeping disturbances	Day 0	Sleep disturbances measured by the Sleep Disturbance Scale for Children (SDSC). SDSC: Scale for assessing sleep disorders comprising 25 items distributed across five factors (trouble initiating or maintaining sleep, parasomnia, excessive daytime sleepiness, sleep-related breathing disorder, non-restorative sleep), with the French version validated for individuals aged 4 to 16 years.
Hyperactivity symptoms	Day 0	Hyperactivity symptoms measured by the Aberrant Behavior Checklist (ABC). ABC: Behavioral assessment scale for individuals aged 5 to 58 years, comprising five subdomains: irritability and agitation, lethargy and social withdrawal, stereotyped behaviors, hyperactivity and non-collaboration, inappropriate speech. Validated tool for individuals with intellectual development disorders and those with autism spectrum disorders.
Autistic symptoms	Day 21	Autistic symptoms measured by the Autism Diagnostic Interview-Revised (ADI-R). ADI-R: Semi-structured interview used for the diagnosis of Autism Spectrum Disorder in individuals with a developmental age beyond 24 months. Four domains are assessed: qualitative abnormalities in reciprocal social interaction; qualitative abnormalities in communication; restricted, repetitive, and stereotyped behaviors; evident developmental abnormalities at or before 36 months.
Behavioral issues	Day 0	Behavioral disorders measured by the Aberrant Behavior Checklist scale (ABC).
General psychopathology	Day 14 (and day 28 with participant if applicable)	General psychopathology measured by the Kiddie-SADS Semi-Structured Interview - Lifetime Version (K-SADS-PL).; K-SADS-PL: Semi-structured diagnostic interview used to assess psychiatric disorders based on DSM-5 criteria in individuals aged 6 to 18 years. The tool includes a screening interview and five additional supplements (addressing mood, psychotic, anxiety, neurodevelopmental, and eating/addictive disorders) that will be administered based on identified signs observed during the screening interview. The K-SADS-PL involves separate interviews with parents and the subject themselves.
Psychotic symptoms	Day 0 and 21	Psychotic symptoms measured by the adapted Glasgow Psychosis Screening Tool (adapted GPS-ID).; Adapted GPS-ID: Screening scale for psychotic symptoms in children with intellectual development disorders, adapted from the Glasgow Psychosis Screening Tool for use in Adults with Intellectual Disabilities (GPS-ID). The adapted scale has not yet been validated.
Sensory peculiarities	Day 0	Sensory peculiarities measured by the Sensory Profile 2. Sensory Profile 2: Scale for assessing sensory integration abilities in individuals aged 7 months to 14 years 11 months, aiming to highlight the reaction profile (seeking, avoidance, sensitivity, registration) across different sensory channels and identify sensory systems (auditory, visual, tactile, proprioceptive, kinesthetic, oral) that may contribute to or hinder daily functional performance.
Anxiety symptoms	Day 0	Anxiety symptoms measured by the Anxiety, Depression and Mood Scale (ADAMS). ADAMS: Scale for assessing anxiety and depressive symptoms in individuals with intellectual development disorders. The psychometric properties of this tool have been established in subjects aged 10 to 79 years of chronological age with mild to profound intellectual development disorders.
Adaptive skills	Day 7	Adaptive skills measured by the Vineland Semi-Structured Interview II (VABS-II).; VABS-II: Semi-structured interview used to assess the level of autonomy and adaptive capabilities in the areas of communication, daily living skills, socialization (and motor skills for individuals under 7 years of chronological age). The tool is applicable across all age groups and has been validated in individuals with intellectual development disorders.

Secondary Outcome Measures

Name	Time	Method
Agitation	Day 0	Agitation measured by the "hyperactivity" subdomain of the Aberrant Behavior Checklist (ABC).
Correlation between agitation and symptoms of attention deficit/hyperactivity disorder on the one hand, and psychotic symptoms on the other hand	Day 0	Assessment of the correlation between agitation measured by the "hyperactivity" subdomain of the Aberrant Behavior Checklist and symptoms of attention deficit/hyperactivity disorder measured by the "hyperactivity" subdomain of the Conners 3, on one hand, and psychotic symptoms measured by the adapted Glasgow Psychosis Screening Tool, on the other hand.
Psychometric properties of the Scale of Attention in Intellectual Disability - Parent version (SAID-P)	23 months	Assessment of the preliminary psychometric properties of the Scale of Attention in Intellectual Disability - Parent version (SAID-P).
Psychometric properties of the adapted Glasgow Psychosis Screening Tool (adapted GPS-ID)	23 months	Assessment of the preliminary psychometric properties of the adapted Glasgow Psychosis Screening Tool (adapted GPS-ID).

Trial Locations

Locations (1)

Hôpital Necker-Enfants Malades; 🇫🇷 Paris, France