FOXP1 SyndromeFOXP1-PPNCT06211673
Psychiatric Phenotype Characterization of Individuals With FOXP1 Syndrome
An observational study of FOXP1 Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- FOXP1 Syndrome
- What is being tested?
- Semi-structured interviews and Heteroquestionnaires
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- 19 Jan 2024to 16 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Minor or adult patient of the Necker-Enfants Malades hospital, without age limit, presenting FOXP1 syndrome secondary to an identified genetic anomaly affecting the FOXP1 gene and the holders of parental authority and legal representatives of patients.
Who may be able to join
- 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.
Who cannot join
- Non French-speaking legal guardians or legal representatives of the patient;
- Illiterate legal guardians or legal representatives of the patient.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Semi-structured interviews, Heteroquestionnaires
- Keywords
- FOXP1 syndrome, hyperactivity, attention disorder, psychotic symptoms, autistic symptoms, sensory peculiarities, anxiety symptoms, sleeping disturbances, behavioral issues, general psychopathology, adaptive skills, agitation
- Medical subject headings
- Spasm, Cognition Disorders, Anxiety Disorders, Parasomnias, Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semi-structured interviewsOther
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.
HeteroquestionnairesOther
Also called 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)
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Semi-structured interviews; Other: Heteroquestionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hyperactivity symptoms
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.
Measured: Day 0
Attention deficit/hyperactivity symptoms
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.
Measured: Day 0 and 21
Psychotic symptoms
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.
Measured: Day 0 and 21
Autistic symptoms
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.
Measured: Day 21
Sensory peculiarities
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.
Measured: Day 0
Anxiety symptoms
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.
Measured: Day 0
Sleeping disturbances
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.
Measured: Day 0
Behavioral issues
Behavioral disorders measured by the Aberrant Behavior Checklist scale (ABC).
Measured: Day 0
General psychopathology
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.
Measured: Day 14 (and day 28 with participant if applicable)
Adaptive skills
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.
Measured: Day 7
Secondary outcomes (4)
Agitation
Agitation measured by the "hyperactivity" subdomain of the Aberrant Behavior Checklist (ABC).
Measured: Day 0
Correlation between agitation and symptoms of attention deficit/hyperactivity disorder on the one hand, and psychotic symptoms on the other hand
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.
Measured: Day 0
Psychometric properties of the Scale of Attention in Intellectual Disability - Parent version (SAID-P)
Assessment of the preliminary psychometric properties of the Scale of Attention in Intellectual Disability - Parent version (SAID-P).
Measured: 23 months
Psychometric properties of the adapted Glasgow Psychosis Screening Tool (adapted GPS-ID)
Assessment of the preliminary psychometric properties of the adapted Glasgow Psychosis Screening Tool (adapted GPS-ID).
Measured: 23 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2024
- Study start19 Jan 2024
- Primary completion16 Jul 2025
- Study completion16 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for FOXP1 SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Maryse Pagnier, MD, Principal investigator, Assistance Publique - Hôpitaux de ParisPauline Chaste, MD, PhD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06211673
- Sponsor's protocol ID
- APHP231331
- Other IDs
- 2023-A01981-44
- Acronym
- FOXP1-PP
- Status last verified
- Sep 2025
- First submitted
- 9 Jan 2024
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alenezi S, Alyahya A, Aldhalaan H. Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) With Language Impairment Accompanied by Developmental Disability Caused by Forkhead Box Protein 1 (FOXP1) Exon Deletion: A Case Report. Cureus. 2021 Dec 22;13(12):e20595. doi: 10.7759/cureus.20595. eCollection 2021 Dec.
PubMed 35103171Bekheirnia MR, Bekheirnia N, Bainbridge MN, Gu S, Coban Akdemir ZH, Gambin T, Janzen NK, Jhangiani SN, Muzny DM, Michael M, Brewer ED, Elenberg E, Kale AS, Riley AA, Swartz SJ, Scott DA, Yang Y, Srivaths PR, Wenderfer SE, Bodurtha J, Applegate CD, Velinov M, Myers A, Borovik L, Craigen WJ, Hanchard NA, Rosenfeld JA, Lewis RA, Gonzales ET, Gibbs RA, Belmont JW, Roth DR, Eng C, Braun MC, Lupski JR, Lamb DJ. Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene. Genet Med. 2017 Apr;19(4):412-420. doi: 10.1038/gim.2016.131. Epub 2016 Sep 22.
PubMed 27657687Chang SW, Mislankar M, Misra C, Huang N, Dajusta DG, Harrison SM, McBride KL, Baker LA, Garg V. Genetic abnormalities in FOXP1 are associated with congenital heart defects. Hum Mutat. 2013 Sep;34(9):1226-30. doi: 10.1002/humu.22366. Epub 2013 Jul 11.
PubMed 23766104Hamdan FF, Daoud H, Rochefort D, Piton A, Gauthier J, Langlois M, Foomani G, Dobrzeniecka S, Krebs MO, Joober R, Lafreniere RG, Lacaille JC, Mottron L, Drapeau P, Beauchamp MH, Phillips MS, Fombonne E, Rouleau GA, Michaud JL. De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. Am J Hum Genet. 2010 Nov 12;87(5):671-8. doi: 10.1016/j.ajhg.2010.09.017. Epub 2010 Oct 14.
PubMed 20950788Horn D, Kapeller J, Rivera-Brugues N, Moog U, Lorenz-Depiereux B, Eck S, Hempel M, Wagenstaller J, Gawthrope A, Monaco AP, Bonin M, Riess O, Wohlleber E, Illig T, Bezzina CR, Franke A, Spranger S, Villavicencio-Lorini P, Seifert W, Rosenfeld J, Klopocki E, Rappold GA, Strom TM. Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits. Hum Mutat. 2010 Nov;31(11):E1851-60. doi: 10.1002/humu.21362.
PubMed 20848658Lozano R, Gbekie C, Siper PM, Srivastava S, Saland JM, Sethuram S, Tang L, Drapeau E, Frank Y, Buxbaum JD, Kolevzon A. FOXP1 syndrome: a review of the literature and practice parameters for medical assessment and monitoring. J Neurodev Disord. 2021 Apr 23;13(1):18. doi: 10.1186/s11689-021-09358-1.
PubMed 33892622Meerschaut I, Rochefort D, Revencu N, Petre J, Corsello C, Rouleau GA, Hamdan FF, Michaud JL, Morton J, Radley J, Ragge N, Garcia-Minaur S, Lapunzina P, Bralo MP, Mori MA, Moortgat S, Benoit V, Mary S, Bockaert N, Oostra A, Vanakker O, Velinov M, de Ravel TJ, Mekahli D, Sebat J, Vaux KK, DiDonato N, Hanson-Kahn AK, Hudgins L, Dallapiccola B, Novelli A, Tarani L, Andrieux J, Parker MJ, Neas K, Ceulemans B, Schoonjans AS, Prchalova D, Havlovicova M, Hancarova M, Budisteanu M, Dheedene A, Menten B, Dion PA, Lederer D, Callewaert B. FOXP1-related intellectual disability syndrome: a recognisable entity. J Med Genet. 2017 Sep;54(9):613-623. doi: 10.1136/jmedgenet-2017-104579. Epub 2017 Jul 22.
PubMed 28735298O'Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet. 2011 Jun;43(6):585-9. doi: 10.1038/ng.835. Epub 2011 May 15.
PubMed 21572417Siper PM, De Rubeis S, Trelles MDP, Durkin A, Di Marino D, Muratet F, Frank Y, Lozano R, Eichler EE, Kelly M, Beighley J, Gerdts J, Wallace AS, Mefford HC, Bernier RA, Kolevzon A, Buxbaum JD. Prospective investigation of FOXP1 syndrome. Mol Autism. 2017 Oct 24;8:57. doi: 10.1186/s13229-017-0172-6. eCollection 2017.
PubMed 29090079Talkowski ME, Rosenfeld JA, Blumenthal I, Pillalamarri V, Chiang C, Heilbut A, Ernst C, Hanscom C, Rossin E, Lindgren AM, Pereira S, Ruderfer D, Kirby A, Ripke S, Harris DJ, Lee JH, Ha K, Kim HG, Solomon BD, Gropman AL, Lucente D, Sims K, Ohsumi TK, Borowsky ML, Loranger S, Quade B, Lage K, Miles J, Wu BL, Shen Y, Neale B, Shaffer LG, Daly MJ, Morton CC, Gusella JF. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell. 2012 Apr 27;149(3):525-37. doi: 10.1016/j.cell.2012.03.028. Epub 2012 Apr 19.
PubMed 22521361Trelles MP, Levy T, Lerman B, Siper P, Lozano R, Halpern D, Walker H, Zweifach J, Frank Y, Foss-Feig J, Kolevzon A, Buxbaum J. Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms. Mol Autism. 2021 Sep 29;12(1):61. doi: 10.1186/s13229-021-00469-z.
PubMed 34588003
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychiatric Phenotype Characterization of Individuals With FOXP1 Syndrome
- ClinicalTrials.gov ID
- NCT06211673
- Acronym / sponsor ID
- FOXP1-PP / APHP231331
- Conditions
- FOXP1 Syndrome
- Keywords
- FOXP1 syndrome, hyperactivity, attention disorder, psychotic symptoms, autistic symptoms, sensory peculiarities, anxiety symptoms, sleeping disturbances
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 19 Jan 2024 (actual)
- Primary completion
- 16 Jul 2025 (actual)
- Study completion
- 16 Jul 2025 (actual)
- First posted
- 18 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients and legal representatives | – | Other: Semi-structured interviews, Other: HeteroquestionnairesMinors 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Minor or adult patient of the Necker-Enfants Malades hospital, without age limit, presenting FOXP1 syndrome secondary to an identified genetic anomaly affecting the FOXP1 gene and the holders of parental authority and legal representatives of patients.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- Non French-speaking legal guardians or legal representatives of the patient;
- Illiterate legal guardians or legal representatives of the patient.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semi-structured interviews3 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. | Other | Patients and legal representatives |
| HeteroquestionnairesAlso: 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)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. | Other | Patients and legal representatives |
Primary outcome
Hyperactivity symptoms
Time frame: 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.
Attention deficit/hyperactivity symptoms
Time frame: 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.
Psychotic symptoms
Time frame: 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.
Autistic symptoms
Time frame: 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.
Sensory peculiarities
Time frame: 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
Time frame: 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.
Sleeping disturbances
Time frame: 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.
Behavioral issues
Time frame: Day 0
Behavioral disorders measured by the Aberrant Behavior Checklist scale (ABC).
General psychopathology
Time frame: 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.
Adaptive skills
Time frame: 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.
4 secondary outcomes
Agitation
Time frame: Day 0
Correlation between agitation and symptoms of attention deficit/hyperactivity disorder on the one hand, and psychotic symptoms on the other hand
Time frame: Day 0
Psychometric properties of the Scale of Attention in Intellectual Disability - Parent version (SAID-P)
Time frame: 23 months
Psychometric properties of the adapted Glasgow Psychosis Screening Tool (adapted GPS-ID)
Time frame: 23 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Background: PubMed 35103171Alenezi S, Alyahya A, Aldhalaan H. Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) With Language Impairment Accompanied by Developmental Disability Caused by Forkhead Box Protein 1 (FOXP1) Exon Deletion: A Case Report. Cureus. 2021 Dec 22;13(12):e20595. doi: 10.7759/cureus.20595. eCollection 2021 Dec.
- Background: PubMed 27657687Bekheirnia MR, Bekheirnia N, Bainbridge MN, Gu S, Coban Akdemir ZH, Gambin T, Janzen NK, Jhangiani SN, Muzny DM, Michael M, Brewer ED, Elenberg E, Kale AS, Riley AA, Swartz SJ, Scott DA, Yang Y, Srivaths PR, Wenderfer SE, Bodurtha J, Applegate CD, Velinov M, Myers A, Borovik L, Craigen WJ, Hanchard NA, Rosenfeld JA, Lewis RA, Gonzales ET, Gibbs RA, Belmont JW, Roth DR, Eng C, Braun MC, Lupski JR, Lamb DJ. Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene. Genet Med. 2017 Apr;19(4):412-420. doi: 10.1038/gim.2016.131. Epub 2016 Sep 22.
- Background: PubMed 23766104Chang SW, Mislankar M, Misra C, Huang N, Dajusta DG, Harrison SM, McBride KL, Baker LA, Garg V. Genetic abnormalities in FOXP1 are associated with congenital heart defects. Hum Mutat. 2013 Sep;34(9):1226-30. doi: 10.1002/humu.22366. Epub 2013 Jul 11.
- Background: PubMed 20950788Hamdan FF, Daoud H, Rochefort D, Piton A, Gauthier J, Langlois M, Foomani G, Dobrzeniecka S, Krebs MO, Joober R, Lafreniere RG, Lacaille JC, Mottron L, Drapeau P, Beauchamp MH, Phillips MS, Fombonne E, Rouleau GA, Michaud JL. De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. Am J Hum Genet. 2010 Nov 12;87(5):671-8. doi: 10.1016/j.ajhg.2010.09.017. Epub 2010 Oct 14.
- Background: PubMed 20848658Horn D, Kapeller J, Rivera-Brugues N, Moog U, Lorenz-Depiereux B, Eck S, Hempel M, Wagenstaller J, Gawthrope A, Monaco AP, Bonin M, Riess O, Wohlleber E, Illig T, Bezzina CR, Franke A, Spranger S, Villavicencio-Lorini P, Seifert W, Rosenfeld J, Klopocki E, Rappold GA, Strom TM. Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits. Hum Mutat. 2010 Nov;31(11):E1851-60. doi: 10.1002/humu.21362.
- Background: PubMed 33892622Lozano R, Gbekie C, Siper PM, Srivastava S, Saland JM, Sethuram S, Tang L, Drapeau E, Frank Y, Buxbaum JD, Kolevzon A. FOXP1 syndrome: a review of the literature and practice parameters for medical assessment and monitoring. J Neurodev Disord. 2021 Apr 23;13(1):18. doi: 10.1186/s11689-021-09358-1.
- Background: PubMed 28735298Meerschaut I, Rochefort D, Revencu N, Petre J, Corsello C, Rouleau GA, Hamdan FF, Michaud JL, Morton J, Radley J, Ragge N, Garcia-Minaur S, Lapunzina P, Bralo MP, Mori MA, Moortgat S, Benoit V, Mary S, Bockaert N, Oostra A, Vanakker O, Velinov M, de Ravel TJ, Mekahli D, Sebat J, Vaux KK, DiDonato N, Hanson-Kahn AK, Hudgins L, Dallapiccola B, Novelli A, Tarani L, Andrieux J, Parker MJ, Neas K, Ceulemans B, Schoonjans AS, Prchalova D, Havlovicova M, Hancarova M, Budisteanu M, Dheedene A, Menten B, Dion PA, Lederer D, Callewaert B. FOXP1-related intellectual disability syndrome: a recognisable entity. J Med Genet. 2017 Sep;54(9):613-623. doi: 10.1136/jmedgenet-2017-104579. Epub 2017 Jul 22.
- Background: PubMed 21572417O'Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet. 2011 Jun;43(6):585-9. doi: 10.1038/ng.835. Epub 2011 May 15.
- Background: PubMed 29090079Siper PM, De Rubeis S, Trelles MDP, Durkin A, Di Marino D, Muratet F, Frank Y, Lozano R, Eichler EE, Kelly M, Beighley J, Gerdts J, Wallace AS, Mefford HC, Bernier RA, Kolevzon A, Buxbaum JD. Prospective investigation of FOXP1 syndrome. Mol Autism. 2017 Oct 24;8:57. doi: 10.1186/s13229-017-0172-6. eCollection 2017.
- Background: PubMed 22521361Talkowski ME, Rosenfeld JA, Blumenthal I, Pillalamarri V, Chiang C, Heilbut A, Ernst C, Hanscom C, Rossin E, Lindgren AM, Pereira S, Ruderfer D, Kirby A, Ripke S, Harris DJ, Lee JH, Ha K, Kim HG, Solomon BD, Gropman AL, Lucente D, Sims K, Ohsumi TK, Borowsky ML, Loranger S, Quade B, Lage K, Miles J, Wu BL, Shen Y, Neale B, Shaffer LG, Daly MJ, Morton CC, Gusella JF. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell. 2012 Apr 27;149(3):525-37. doi: 10.1016/j.cell.2012.03.028. Epub 2012 Apr 19.
- Background: PubMed 34588003Trelles MP, Levy T, Lerman B, Siper P, Lozano R, Halpern D, Walker H, Zweifach J, Frank Y, Foss-Feig J, Kolevzon A, Buxbaum J. Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms. Mol Autism. 2021 Sep 29;12(1):61. doi: 10.1186/s13229-021-00469-z.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maryse Pagnier, MD principal investigator
Assistance Publique - Hôpitaux de Paris
Pauline Chaste, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of FOXP1 Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hyperactivity symptoms (time frame: Day 0). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06211673, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.