Further Delineation of the De Santo Shinawi Syndrome Phenotype Using a Series of Individuals Carrying a Pathogenic Variant of the WAC Gene (2024-CF366)

The aim of this retrospective, multicenter study would be to extend the phenotypic spectrum of DeSanto Shinawi Syndrome and improve the knowledge of its evolution. To this end, the investigators would like to issue a call for international collaboration in order to create a series of new genetically diagnosed patients, not yet described in previous publications, and with a larger number of individuals evaluated in a single study. One of the aims would be to establish a set of standardized clinical and paraclinical examinations to be carried out at diagnosis and for follow-up of affected patients. This would enable patients, their families and the caregivers involved to better anticipate future management.

Study Overview

• Status: Recruiting
• Conditions: WAC; DeSanto-Shinawi Syndrome; DESSH; WAC SYNDROME; OMIM#616708; ORPHA:466943

Detailed Description

Main objective :

Update clinical and paraclinical knowledge of DeSanto-Shinawi syndrome.

Secondary objectives:

• Inventory the clinical signs of the syndrome described to date and look for recurrence between patients.
• Select a set of standardized clinical and paraclinical examinations for diagnosis.
• Establish appropriate management and follow-up.
• To compare the phenotype of patients with DESSH due to a pathogenic point variation in the WAC gene and those with a microdeletion involving the WAC gene.

Main inclusion criteria:

Children and adults of any age. Molecular diagnosis of a pathogenic variant involving the WAC gene (SNV, CNV, SV).

Main non-inclusion criteria:

Patients with a molecular diagnosis of another VP (SNV) of a gene responsible for a neurodevelopmental disorder.

Patient having already participated in a DESSH study with published data. No patient data available.

Primary endpoint:

The data collected will enable the investigators to meet the objective, namely to expand clinical and paraclinical knowledge of DeSanto-Shinawi syndrome.

Main secondary endpoints: NA (descriptive study) Statistics: NA (descriptive study)

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: 334.73.754.963; Email: promo_interne_drci@chu-clermontferrand.fr

Study Locations

• France
  • Auvergne
    • Clermont-Ferrand,, Auvergne, France, 63000
      • Recruiting
      • Clermont-Ferrand University Hospital
      • Contact: Florian CHERIK; Phone Number: +33473750654; Email: fcherik@chu-clermontferrand.fr
      • Contact: Marie-Gabrielle DELORME GUINAND; Email: mgdelormeguinand@chu-clermontferrand.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients of any age with a molecular and clinical diagnosis of DeSanto-Shinawi Syndrome.

Description

Inclusion Criteria:

• Children and adults of any age.
• Molecular diagnosis of a pathogenic (or likely pathogenic) variant involving the WAC gene (SNV, CNV, SV).

Exclusion Criteria:

• Patients with a molecular diagnosis of another VP (SNV) of a gene responsible for a neurodevelopmental disorder.
• Patient having already participated in a DESSH study with published data.
• No patient data available.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Serie of patients with a molecular diagnosis of DeSanto-Shinawi Syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical knowledge	Morphologic description with photos (optional) at a specified date (front and side of the face, hands-feet : plant and palm) using HPO terms	Through study completion, an average of 2 years
Clinical knowledge	Overall clinical examination and interrogatory at the last medical consultation (neurologic, cardiologic, gastroenterologic, pulmonary, urinary, global development, etc.) : data collected using a redcap form.	Through study completion, an average of 2 years
Clinical knowledge	Height, weight and head circumferance at birth and at last visit	Through study completion, an average of 2 years
Paraclinical knowledge	Any psychometric scale performed during lifetime : Language delay, Motor delay, ADHD, IQ, ASD	Through study completion, an average of 2 years
Paraclinical knowledge	Any exams performed during lifetime : EEG, neuroMRI, abdominal echography, cardiac echography	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of clinical signs	Inventory the clinical signs of the syndrome described to date and mesure concordance or not	Through study completion, an average of 2 years
Standardized examinations	Using concordance of signs, mesure the clinical and paraclinical necessary at diagnosis	Through study completion, an average of 2 years
Management & Follow-up	Using concordance of signs at different ages, establish appropriate management and follow-up.	Through study completion, an average of 2 years
Genotype phenotype correlation	Compare the phenotype of DESSH patients with pathogenic point variation in the WAC gene and those with microdeletion involving the WAC gene	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Florian CHERIK, University Hospital, Clermont-Ferrand

Publications and helpful links

Helpful Links

• Patients with DeSanto-Shinawi syndrome: Further extension of phenotype from Italy; Pasquali et al.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: January 29, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Further delineation of the De Santo Shinawi Syndrome; Serie of patients with DESSH; Better characterization of DeSanto-Shinawi Syndrome; Series of individuals with pathogenic WAC variant; WAC; DeSanto; DeSanto-Shinawi; De Santo Shinawi; DESSH; OMIM 616708; OMIM#616708; ORPHA:466943; ORPHA 466943
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome
• Other Study ID Numbers: 2024-CF366

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No