الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Prenatal onset growth deficiency is a very heterogeneous group of disorders, caused by both genetic and environmental factors. IUGR is an important cause of fetal and neonatal morbidity and mortality. In Egypt, LBW rate is about 12% among live births.
Optimal fetal growth is a multifactorial process, with both genetic and environmental factors thought to contribute in equal parts. It is usually end results of maternal, placental, and fetal causes. Nearly one-third of IUGRs are due to genetic causes, and two-thirds are related to the fetal environment.
There are a wide variety of fetal malformation syndromes caused by single gene disorders, chromosomal disorders, teratogens, or in utero infections in which fetal hypoplasia is part of the overall disorder
Genomic imprinting plays a critical role in several aspects of pre- and postnatal life. Silver Russell syndrome is the most prominent growth restriction syndrome with epigenetic alterations.
The aim of the work was to study different syndromes with prenatal onset growth deficiency among a group of Egyptian patients. This would allow accurate diagnosis, proper management and genetic counseling. The study also aimed to assess the methylation status of H19 imprinting control region 1 in clinically suspected patients of Silver Russell syndrome.
The study was conducted on 40 patients with prenatal growth deficiency, referred to the Human Genetics Department, Medical Research Institute, Alexandria University.
All the patients were subjected to detailed genetic history taking, pregnancy and delivery history, complete clinical genetic examination with special emphasis on anthropometric measurements, pedigree analysis, clinical photography, chromosomal analysis and various investigations according to individual cases. The clinically suspected SRS were included in the molecular study using MS-MLPA for assessment of methylation status and copy number variation within several imprinted regions including 11p15.
The results of this study revealed the following:
Among all studied patients, 25 (62.5%) were females and 15 (37.5%) were males. All of selected cases had low birth weight; ranging from 750 to 2400 grams. Their ages ranged from 5 days to 27 years. Parental consanguinity was detected in 20 cases (50%).
According to the underlying etiology of the prenatal onset growth deficiency, the studied cases were categorized into three groups:
group I: Patients with chromosomal abnormalities; 13 cases (32.5%).
This group of patients included:
- Trisomy 18 (3 cases, 7.5%)
- Trisomy 13 (2 cases; one standard and one translocated, 5%)
- Turner syndrome (2 cases, 5%)
- Deletion 13q syndrome. (1 case, 2.5%)
- Partial trisomy 7p (1 case, 2.5%)
Summary
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- One patient with inversion duplication of chromosome 2p (2.5%)
- One patient with complex mosaic chromosome 18 abnormalities (2.5%)
- Deletion 4p syndrome (1 case, 2.5%)
- Williams syndrome (1 case, 2.5%)
group II: Patients with malformation syndromes; 26 cases (65%).
group II was sub-classified into:
A. Clinically suspected RSS group; 9 cases (22.5%).
B. Miscellaneous malformation syndromes group; 17 cases (42.5%). This group included:
- Sanjad-Sakati syndrome (3 cases, 7.5%)
- Cornelia De Lange syndrome (2 cases, 5%)
- Fanconi anemia (2 cases, 5%)
- Coffin-Siris syndrome (2 cases, 5%)
- Holoprosencephaly (2 case, 5%)
- Nicolaides-Baraitser syndrome (1 case, 2.5%)
- Johanson–Blizzard syndrome (1 case, 2.5%)
- Cockayne syndrome (1 case, 2.5%)
- Bloom syndrome (1 case, 2.5%)
- Matthew-Wood syndrome (1 case, 2.5%)
- Shprintzen-Goldberg syndrome (1 case 2.5%)
group III: Patient with a teratogenic disorder; 1 case (2.5%).
Molecular studies for certain patients
• Molecular results for SRS group
- The methylation patterns of the targeted chromosomal regions were within normal ranges in all studied cases (8/8; 100%).
- In addition, no copy number variations (deletions/duplications) were detected in all studied cases (8/8; 100%).
- The results of microarray study were normal for SRS group, but detected submicroscopic deletion in patient with 4p deletion syndrome (this patient was included among the group of chromosomal abnormalities).
• Molecular testing for cases Sanjad-Sakati syndrome: a 12 base pair deletion of exon 3 of TBCE gene detected by Sanger sequencing.
• Molecular genetic testing for Johanson–Blizzard syndrome: a homozygous mutation
(c.1183-8T>G) was identified in the UBR1 gene.
• Whole exome sequencing for Shprintzen-Goldberg syndrome: revealed a missense mutation [NM_003036.3:c.347G>A (p.Gly116Glu)] in SKI gene.