Objective
Microdeletional syndromes are rare genetic pathologies, defined as the presence of loss of small chromosomal fragments (< 5 megabases), not visible on a standard karyotype. These microdeletions are detectable only by the use of molecular cytogenetics, the most commonly used in medical practice being Fluorescent In Situ Hybridization FISH, which locates a specific sequence using a complementary probe of fluorescently-labeled DNA. In most cases, de novo deletions are involved; not transmitted by the parents but linked to a meiotic accident. The aim is to study the clinical and evolutionary features of microdeletional syndromes diagnosed in the neonatal period in the neonatology department of Farhat Hached hospital in Sousse, Tunisia.
Methods
A retrospective, descriptive study of all microdeletional syndromes diagnosed in the neonatology department of Sousse, over a 10-year period (January 2014- December 2023). Diagnostic orientation was essentially clinical, radiological and biological. The molecular genetic study was carried out in the Cytogenetics Department of the same hospital, based on karyotyping with FISH and molecular analysis using multiplex PCR.
Results
We collected 24 cases of microdeletional syndromes, equally distributed between males and females. Diagnosis was made antenatally in 3 cases. Prematurity was found in 7 cases. Signs suggesting a karyotype and molecular study were facial dysmorphia (15 cases), congenital heart disease (13 cases), unexplained hypotrophy (11 cases) and neurological distress (10 cases). The various microdeletional syndromes diagnosed by the FISH technique were, in order of frequency : DiGeorge syndrome (13 cases), Prader Willis syndrome (8 cases), Williams and Beuren syndrome (1 case), 1p36 syndrome (1 case) and cat's cry syndrome (1 case). The molecular alterations observed enabled us to establish a genotype/phenotype correlation between the genetic abnormality and the clinical presentation of our patients.
Conclusion
The contribution of molecular cytogenetics (FISH) is crucial for the investigation of microdeletional syndromes, with the aim of confirming the diagnosis, genetic counseling and management, which is usually multidisciplinary. At the end of this work, we have determined the optimal molecular diagnostic strategy for all microdeletional syndromes that can be diagnosed in the neonatal period, while focusing on the role of genetic counselling and prenatal diagnosis.
Keywords
Microdeletional syndrome, FISH, molecular cytogenetics, genetic counseling.
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Figure 1 Clinical symptomatology |
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Figure 2 The microdeletional syndromes diagnosed |