الفهرس 
SHORT STATUREOnly 14 pages are availabe for public view
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Abstract
Short stature is a condition in which the height of the person is more than 2 SD below the meanheight for a given age and sex in a population. Appropriate diagnosis and treatment of short children can avert excessive short stature in adult life. In poor and developing nations short stature affects up to 20% of its adult population, which in turn unfavorably impact their economy.
Most of children with non-syndromic short stature after exclusion of systemic diseases and GH deficiency are sub classified under idiopathic short stature, or small for gestational age. Though, the distinction between these sub classes can be tough. Thorough medical history, a physical examination, and prompt laboratory tests can exclude systemic diseases and GH deficiency. Proper genetic testing of the remaining children allows proper sub classification and hence proper therapeutic intervention.
The most common causes of short stature past the first two years of life are familial short stature (genetic) and Constitutional delay of growth and puberty, which are normal variants of growth. In developing countries the commonest causes of short stature is protein energy malnutrition and chronic diseases including infections.
Previous studies showed overall short stature constituted 17% of Egyptian school children of those anemia associated with stunting was reported in 9.9% due to malnutrition.
Idiopathic short statureis defined as short stature with no apparent etiology. This means that, it should be distinguished from dysmorphic syndromes, skeletal dysplasias, short stature secondary to a small birth size (small for gestational age), and systemic and endocrine diseases. In other word, ISS is the remaining diagnosis after eliminating other causes of short stature.
This study tried to evaluate the role of IGF1R, IGFBP3, IGFALS gene copy number variations in idiopathic short stature and to assess the role of different environmental factors affecting stature. It also tried to assess the usefulness of MLPA technique in detecting CNVs in the previously mentioned genes in Egyptian stunted children.
Multiplex Ligation-dependent Probe Amplification (MLPA®) is a high-throughput technique that was invented to identify the CNV of 50 genomic DNA locations in a one multiplex PCR-based reaction. The reaction needs only a small amount of DNA sample to be performed, It can identify sequences that differ in a single nucleotide only, and needs no specific equipment only a thermocycler and a sequencer available in most molecular biology labs. Furthermore it’s cheap and easy to perform. MLPA should be used as an initial screening technique in short children. Proper genetic diagnosis of these children leads to implementation of appropriate therapeutic approaches.It has been determined by previous studies that MLPA is a useful tool to detect submicroscopic deletions of the IGF1R gene.
The present study was conducted on 41 children with short stature 30 cases with ISS and 11 cases had growth hormone deficiency compared to 40 heathy children with matched age and sex. The study group were composed of 6 males 35 females, their age ranged from 2 years to 16 years old. Hormonal assessment of TSH, T3, and T4 were normal in all studied cases. GH was low in 11 cases and normal in the remaining 30 cases “ISS” cases.
All patients underwent complete history taking including interview environmental risk factor questionnaire, pedigree analysis and clinical examination. Conventional cytogenetic analysis and MLPA screening for copy number variations ofIGF1R, IGFALS, and IGFBP3 genes were performed for all patients in the study.
Only patients with normal karyotype wereincluded in the study. MLPA screening for copy number variations of IGF-1Rgene detected one patient (2.4%) with a deletion of exons 4-21 of IGF1R.IGFALS, and IGFBP3 genesin all patients were normal.
In This study we tried to investigate the probable role of some widespread environmental factors in children with short stature.
The studied group showed significantly higher median number of siblings, higher frequency of consanguinity, lower socioeconomic grade and increased crowding index. Short stature group had also higher frequency of family history and significantly higher delayed bone age but with no significant pubertal delay.
When studying the paternal risk factors we found that short stature group was associated with significantly shorter fathers, higher frequency of illiteracy among fathers, higher frequency of worker as a father’s job (non-skilled workers)
When analyzing maternal risk factors short stature was significantly associated with younger and shorter mothers, higher frequency of lower educational levels as well as lower frequency of higher educational levels in mother when compared to normal stature group. Short stature group was significantly associated with house wife as a mother’s job.
Conclusion:
This study detected various significant environmental factors affecting stature including (Consanguinity, number of siblings, crowding, socioeconomic status, maternal age, parental height, and paternal and maternal level of education. Short stature was also associated with delayed bone age and lighter weight.
Despite of our small sample size that limit the study, we were able to identify a familial short stature case with heterozygous IGF1R partial deletion in a group of Egyptian non-syndromic short stature patients.
MLPA was able to detect the underlying genetic CNVs in (2.4%) of the study cases. Screening with MLPA for CNVs of IGF1R and other genes that are considered key regulators of human height such as SHOX and GH could subsequently be a fast and low-cost diagnostic instrument to recognize a subgroup of patients in which GH treatment could be implemented.