Psychiatric Phenotype Characterization of Individuals With FOXP1 Syndrome

NCT ID: NCT06211673

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 25 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-01-19
• Study Completion Date: 2025-07-16

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.

Conditions

FOXP1 Syndrome

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients and legal representatives

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.

Semi-structured interviews

Intervention Type: OTHER

3 semi-structured interviews will be administered to the legal guardians or legal representative of the patient:

• Vineland Adaptive Behavior Scales II (VABS-II): assessment of adaptive skills;
• Kiddie-SADS-Lifetime Version (K-SADS-PL): assessment of general psychopathology;
• Autism Diagnostic Interview-Revised (ADI-R): assessment of autistic symptoms. The K-SADS-PL will be administered directly to the participant provided the participant is of an equivalent age of at least 5 years 11 months for receptive language and expressive language on the VABS-II, with raw scores of 35 and 92, respectively.

Heteroquestionnaires

Intervention Type: OTHER

7 heteroquestionnaires assessing: Hyperactivity symptoms and behavioral disorders measured by the ABC Attention deficit/hyperactivity symptoms measured by the Conners 3 scale and the SAID-P Psychotic symptoms measured by the adapted GPS-ID Sensory peculiarities measured by the Sensory Profile 2 Anxiety symptoms measured by the ADAMS Sleep disorders measured by the SDSC For children, the questionnaires: ABC, Sensory Profile 2, ADAMS, SDSC will be completed collectively by the legal guardians, and the questionnaires: Conners 3, SAID-P, adapted GPS-ID will be independently completed by each legal guardian. The same for adult patients with possible second caregiver. The questionnaires Conners 3, SAID-P and adapted GPS-ID will be completed twice, with a 28-day interval, at the time of inclusion and then after the semi-structured interviews.

Interventions

Semi-structured interviews

3 semi-structured interviews will be administered to the legal guardians or legal representative of the patient:

• Vineland Adaptive Behavior Scales II (VABS-II): assessment of adaptive skills;
• Kiddie-SADS-Lifetime Version (K-SADS-PL): assessment of general psychopathology;
• Autism Diagnostic Interview-Revised (ADI-R): assessment of autistic symptoms. The K-SADS-PL will be administered directly to the participant provided the participant is of an equivalent age of at least 5 years 11 months for receptive language and expressive language on the VABS-II, with raw scores of 35 and 92, respectively.

Intervention Type: OTHER

Heteroquestionnaires

7 heteroquestionnaires assessing: Hyperactivity symptoms and behavioral disorders measured by the ABC Attention deficit/hyperactivity symptoms measured by the Conners 3 scale and the SAID-P Psychotic symptoms measured by the adapted GPS-ID Sensory peculiarities measured by the Sensory Profile 2 Anxiety symptoms measured by the ADAMS Sleep disorders measured by the SDSC For children, the questionnaires: ABC, Sensory Profile 2, ADAMS, SDSC will be completed collectively by the legal guardians, and the questionnaires: Conners 3, SAID-P, adapted GPS-ID will be independently completed by each legal guardian. The same for adult patients with possible second caregiver. The questionnaires Conners 3, SAID-P and adapted GPS-ID will be completed twice, with a 28-day interval, at the time of inclusion and then after the semi-structured interviews.

Intervention Type: OTHER

Other Intervention Names

Aberrant Behavior Checklist (ABC); Conners 3 scale; Scale of Attention in Intellectual Disability -Parent version (SAID-P); Adapted Glasgow Psychosis Screening Tool (adapted GPS-ID); Sensory Profile 2; Anxiety, Depression and Mood Scale (ADAMS); Sleep Disturbance Scale for Children (SDSC)

Eligibility Criteria

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.

Exclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maryse Pagnier, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Pauline Chaste, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Necker-Enfants Malades

Paris, , France

Countries

France

References

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Other Identifiers

2023-A01981-44

Identifier Type: OTHER

Identifier Source: secondary_id

APHP231331

Identifier Type: -

Identifier Source: org_study_id