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.

The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed.

Low vitamin B12 is a risk factor for having a fetus with neural tube defects. The monitoring of MMA and Hcy levels might be important in understanding and following cases with neural tube defects. Adding vitamin B12 to folic acid may help to decrease the incidence of neural tube defects in the Egyptian population.

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The purpose of this study was to determine whether the levels of cystatin C and beta-2 microglobulin (B2M) are altered during the second trimester in the plasma of women who subsequently develop preeclampsia. Study design: We performed a case control study to compare the levels of cystatin C and B2M in women in whom preeclampsia ultimately developed (n = 30) and in pregnant women who remained normotensive throughout gestation (n = 60). The maternal plasma levels of cystatin C and B2M were measured by enzyme-linked immunosorbent assay. Blood samples were collected between 15 and 20 weeks' gestation for fetal aneuploidy screening and frozen at À20°C until assay after groups had been selected. Results: The median concentrations of cystatin C and B2M were significantly higher in those who subsequently developed preeclampsia when compared to those of normal pregnancy (median 668.6 ng/ml and 418.3 lg/ml vs 413.7 ng/ml and 321.2 lg/ml, respectively). Conclusions: In this study, the maternal plasma levels of cystatin C and B2M were significantly elevated in pregnant women who subsequently developed preeclampsia as compared with