"Familial" versus "Sporadic" intellectual disability: contribution of common microdeletion and microduplication syndromes

Maryam Rafati,Marzieh Purhoseini,Jila Dastan,Mohammad R Ghadirzadeh,Mohammad R Eshraghian,Homeira Adibi,Gholam Reza Javadi,Elaheh Seyyedaboutorabi,Alireza Mosavi-Jarrahi,Yaser Heshmati,Saeed R Ghaffari,Zarrintaj Keihanidoust,Azadeh Hoseini

doi:10.1186/1755-8166-5-9

Abstract

BackgroundInterstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been investigated. As the balanced chromosomal abnormalities commonly lead to the recurrent ID or multiple congenital anomalies, this study was designed to evaluate whether it was justified to investigate such aberrations in familial ID patients. Three hundred and twenty eight patients from 101 unrelated Iranian families with more than two ID patients in the first-degree relatives, have been investigated. Assessment of a panel of 21 common Microdeletion and Microduplication syndromes (CMMS) was carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA) technique.ResultsAmong the families studied, 27.7% had 4-12, 35.6% had 3 and 36.6% had 2 affected individuals in the first-degree relatives. An autosomal dominant inheritance of Williams-Beuren syndrome (WBS) was detected in a family with no clinical suspicion of WBS. The prevalence of CMMS was therefore,0.99%.ConclusionThis is the first investigation of a panel of CMMS in a large sample set of "familial ID patients". The findings of this study showed the low prevalence of CMMSs in "familial ID" patients in spite of the significant contribution of such aberrations in "sporadic ID" which has a very useful practical impact by avoiding unnecessary diagnostic tests in "familial ID" patients.

Highlights

Interstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been investigated
Cytogenetic abnormalities including interstitial microdeletion or microduplication syndromes are considered as the major cause of idiopathic sporadic ID [7,8]
This study is the first investigation of a large sample set of familial ID cases to evaluate the contribution of common Microdeletion and Microduplication syndromes (CMMS) in familial ID which showed that it was not as much as what had been determined for sporadic ID. These findings show that CMMSs do not significantly contribute to familial ID

Summary

Introduction

Interstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been investigated. As the balanced chromosomal abnormalities commonly lead to the recurrent ID or multiple congenital anomalies, this study was designed to evaluate whether it was justified to investigate such aberrations in familial ID patients. Determining a specific genetic diagnosis facilitates both comprehensive medical care and accurate recurrence risk assessment for the family. As familial ID has a much lower incidence in western countries, its genetic basis has not been investigated to the extent of sporadic ID. Familial ID could be due to both chromosomal abnormalities and single gene disorders.

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Discussion

Conclusion