IMPORTANCEThe study establishes the importance of genetic background for the expression of Down syndrome phenotype.OBJECTIVE To define the ocular manifestations of Down syndrome in infants and children in Cairo, Egypt, a historically isolated region, and compare them with systemic features and with findings in other geographic groups. DESIGN AND PARTICIPANTSWe prospectively studied the ocular status and systemic features of 90 infants and children with Down syndrome and monitored all patients for 3 years. The complete ophthalmic examinations were performed along with ultrasonography, if media opacities were evident. Thyroid and cardiac status were assessed. An extensive literature search for comparison was performed.SETTING Outpatient clinical genetics department at the National Research Centre in Cairo, Egypt. MAIN OUTCOMES AND MEASURESOcular and systemic manifestations of Down syndrome in infants and children in Cairo, and comparison of these features with patients with this anomaly from other geographic regions and ethnic populations.RESULTS Fifty-two infants or children (58%) had at least 1 abnormal ocular finding identified at the first visit. Significant refractive errors (in 37 [41%] patients) were the most common. Nasolacrimal duct obstruction, blepharoconjuctivitis, or conjunctivitis was found in 18 (20%), strabismus in 13 (14%), cataract in 5 (6%), nystagmus in 3 (3%), and optic nerve dysplasia in 2 (2%). Brushfield spots were not found. Additional ocular features developed over time. Thirty-six patients (40%) had congenital heart defects, and many (31 [86%]) had associated ocular disorders; a statistically significant correlation with myopia was established. Chromosomal translocations were high. The phenotype in Cairo was distinct.CONCLUSIONS AND RELEVANCE More than half of infants and children with Down syndrome in Cairo had ophthalmic abnormalities; myopia was correlated with congenital heart defects. Comparison of the specific ocular features in our population with those in previous worldwide studies shows differences that may be related to overexpression or polymorphisms of key, modifying genes or other mutations in this historically isolated region along the Nile River. Down syndrome is more common in the highly consanguineous and multiparous Middle Eastern populations, and our Cairo findings underscore regional differences.

Roberts syndrome and SC phocomelia syndrome are rare autosomal recessive genetic disorders representing the extremes of the spectrum of severity of the same condition, caused by mutations in ESCO2 gene. We report three new patients with Roberts syndrome from three unrelated consanguineous Egyptian families. All patients presented with growth retardation, mesomelic shortening of the limbs more in the upper than in the lower limbs and microcephaly. Patients were subjected to clinical, cytogenetic and radiologic examinations. Cytogenetic analysis showed the characteristic premature separation of centromeres and puffing of heterochromatic regions. Further, sequencing of the ESCO2 gene identified a novel mutation c.244_245dupCT (p.T83Pfs*20) in one family besides two previously reported mutations c.760_761insA (p.T254Nfs*27) and c.764_765delTT (p.F255Cfs*25). All mutations were in homozygous state, in exon 3. The severity of the mesomelic shortening of the limbs and craniofacial anomalies showed variability among patients. Interestingly, patient 1 had abnormal skin hypopigmentation. Serial fetal ultrasound examinations and measurements of long bones diagnosed two affected fetuses in two of the studied families. A literature review and case comparison was performed. In conclusion, we report a novel ESCO2 mutation and expand the clinical spectrum of Roberts syndrome.

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Background Retinopathy is one of the major causes of visual impairment which is the most severe microvascular complication of diabetes mellitus (DM). The aim of this study was to evaluate the association between diabetic retinopathy (DR) and two SNPs (− 152G > A and − 165C > T) located in the promoter region of the vascular endothelial growth factor (VEGF) gene in a small sample from Egyptian population. One hundred diabetic patients without retinopathy (DWR) and two hundred diabetic patients with retinopathy were included in this study. Genotype analysis for the two SNPs (− 152G > A and − 165C > T) was assessed by using the PCR–RFLP technique. In addition, the serum protein level of VEGF was measured by ELISA assay. Results The results showed a significant relationship between − 152G > A (rs13207351) polymorphism and both proliferative and non-proliferative retinopathy in genotypes (GG, GA, AA). The risk factor increment in the mutant heterozygous genotype (GA) was significantly increased in NPDR compared to PDR (OR = 16.3, 95%CI = 0.80–331.7); (OR = 20.4, 95%CI = 1.08–385.3), respectively. There was no significance between VEGF − 165C > T (rs79469752) gene polymorphism and retinopathy. Moreover, the serum protein level of VEGF showed a highly significant increase (P = 0.0001) in PDR (Mean ± SD = 3691 ± 124.9) when compared to both DWR (Mean ± SD = 497.3 ± 18.51) and NPDR (Mean ± SD = 1674.5 ± 771.7). These results were supported by the increased level of VEGF in serum protein which is positively correlated with the severity of retinopathy. Measuring VEGF protein level in DR patients would help as a biomarker in early diagnosis. Conclusion The increase in the mutant heterogeneous GA genotype in VEGF − 152G > A SNP could be a risk factor for the progression of severe retinopathy in diabetic patients.