French Kabuki Syndrome Network. Epidemiology, Management of Patients and Research by Array-CGH (Kabuki)

Create a census for the duration of the search for French patients with SK

• determining epidemiological and morphological parameters,
• determine the true frequency of clinical symptoms and identify new ones,
• identify complications of the disease to improve the care of patients in the hope of a better prognosis of the disease and
• performing a radiological study by Voxel based morphometry MRI type (N. BODDAERT, HOPITAL Necker-Enfants Malades, Paris)

Perform genetic research to identify the genetic bases of SK using CGH-array (Comparative Genomic Hybridization )

Study Overview

• Status: Completed
• Conditions: Kabuki Syndrome

Detailed Description

Kabuki syndrome (KS) is a rare syndrome, sporadic dominant condition with a frequency of 1 / 35000 (between 20 and 25 new children by year in France). Five cardinal criteria have been described for this diagnosis: postnatal growth retardation, mild to moderate mental retardation, skeletal abnormalities, dermatoglyphic abnormalities and characteristic facial dysmorphism. Moreover, a large number of other symptoms are described in KS. Each year, new symptoms are reported in the international literature but without their true frequency or recommendations for the management of patients. However, these criteria are not always present in patients and there is no major or minor criteria for establishing the diagnosis. Nowadays, knowledge of this syndrome is still very fragmentary. At the date of the creation of the network, no molecular basis has been identified for the SK.

We propose to create a national network of geneticists including 18 centers labeled "developmental defects" and / or mental retardation in France gathered in Federation Development Centers labeled anomalies (the FECLAD, Head, Professor A VERLOES, Hospital Robert Debré, Paris). We will also rely on Kabuki Syndrome Association that gives us logistical support with families.

The objective of the French Kabuki syndrome network of (FKSN) is to establish a national network to:

1. create a census for the duration of the search for French patients with SK (expected number of patients = 110) for

   • determining epidemiological and morphological parameters,
   • determine the true frequency of clinical symptoms and identify new ones,
   • identify complications of the disease to improve the care of patients in the hope of a better prognosis of the disease and
   • performing a radiological study by Voxel based morphometry MRI type (N. BODDAERT, HOPITAL Necker-Enfants Malades, Paris)

   And

2. perform genetic research to identify the genetic bases of SK using CGH-array (Comparative Genomic Hybridization ).

The RFSK will be responsible for recruiting and evaluating patients with SK, the data collection and informed consent from patients for participation in the project and the establishment of rules for management of patients.

We will also perform MRI Voxel based morphometry in a small cohort of 10 patients aged 8 to 15 years to identify abnormal brain region distribution in patients with abnormal SK. The cohort of patients will be paired with SK-age compared to a historical control cohort and the cohort of patients with SK will be in uniform after the completion of IQ-type test WISC-Wechsler Intelligence Scale for Children-IV (tests performed routinely in all center for each patient).

The RFSK will also be responsible for collecting blood samples with informed consent of patients for molecular studies. These samples will be centralized in the CRB's Hospital Necker-Enfants Malades (Head: Prof. CORINNE ANTIGNAC) for the establishment of lymphoblastoid lines and bases of white blood cells.

Because of the lack of standard methodology of studies of candidate genes relevant in the rare disease, we will take genetic research, using these samples to identify the genetic basis of KS using array CGH high density (44000 clones) on an AGILENT platform (Dr. D SANLAVILLE, Lyon). This research, already used successfully in other sporadic dominant rare diseases (such as CHARGE syndrome), we may help to identify an anomaly INFRACYTOGENETIQUE to locate the gene responsible for SK.

• Study Type: Observational
• Enrollment (Actual): 110

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Department of Genetic, Necker Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Cross-sectional multicenter exploratory and observational study

Description

Inclusion criteria :

• diagnosis based on the decision of National Network of Geneticists
• signed informed consent by the 2 parents
• signed informed consent by the 2 parents to participate to molecular study

Exclusion criteria :

• absence of social insurance
• refusal of the patient and /or parents to participate in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determining epidemiological and morphological parameters	determining epidemiological and morphological parameters,; determine the true frequency of clinical symptoms and identify new ones,; identify complications of the disease to improve the care of patients in the hope of a better prognosis of the disease; performing a radiological study by Voxel based morphometry MRI type	2 YEARS

Secondary Outcome Measures

Outcome Measure	Time Frame
Perform genetic research to identify the genetic bases of SK using CGH-array	2 YEARS

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Stanislas LYONNET, PU-PH, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: March 11, 2011
• First Submitted That Met QC Criteria: March 11, 2011
• First Posted (Estimate): March 14, 2011

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Genetic; Kabuki syndrome; CGH-array
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Congenital Abnormalities; Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Syndrome; Hematologic Diseases; Vestibular Diseases; Abnormalities, Multiple
• Other Study ID Numbers: AOM 07-090 / P070130; IDRCB 2007-A00912-51 (Other Identifier: AFSSAPS)