Association between biomarkers of vitamin B12 status and the risk of neural tube defects.

AIM: The aim of this study was to evaluate the association between vitamin B12 and its biomarkers and the risk of neural tube defects. METHODS: A total of 120 pregnant Egyptian women were included in the study. They were classified into two groups. Group A consisted of 50 women with neural tube defects in current pregnancy or with a history in previous pregnancies, and Group B consisted of 70 women with no history of neural tube defects in previous pregnancies or in the current pregnancy. All women were subjected to ultrasound anomaly scan and serum analysis of vitamin B12, homocysteine (Hcy), methyl malonic acid (MMA) and active vitamin B12 concentrations. Receiver operating characteristic curve analysis was used to determine the best cut-off values of vitamin B12. RESULTS: Serum levels of vitamin B12 were decreased in Neural tube defects (NTDs) cases compared to controls (2.736 vs 3.091 ng/mL; P = 0.0015), while Hcy and MMA concentrations were elevated (18.39 vs 13.95 µmol/L; P = 0.0008 and 263 vs 229.7 µmol/L; P = 0.003, respectively). Active vitamin B12 reduction was not statistically significant (96.8 vs 99.36 pmol/L; P = 0.8013). The optimal cut-off value of vitamin B12, 2.9 ng/mL, is the best threshold to expect neural tube defects, with a sensitivity of 60% and specificity of 74.29%. CONCLUSION: 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.

Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal recessive developmental brain malformation phenotype.

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.

Maternal vitamin B12 and the risk of fetal neural tube defects in Egyptian patients.

OBJECTIVE: Folic acid insufficiency is a known risk factor for neural tube defects (NTDs), while the role of vitamin B12 is questionable. Thus, our purpose was to investigate whether low maternal serum vitamin B12 is associated with an increased risk of NTDs. SETTING: Prenatal Diagnosis and Clinical Genetics Clinics, National Research Centre, in collaboration with the Radioisotope Department, Nuclear Research Centre, Cairo. MATERIALS AND METHODS: The study groups included 36 women who were, or had been, pregnant with a NTD-affected fetus. The control groups comprised 35 healthy women with normal prior or current pregnancy and uncomplicated obstetric histories. Fasting plasma homocysteine, serum folate and cobalamin (vitamin B12) were determined. Odds ratio (OR) and 95% confidence intervals were calculated. RESULTS: The fasting homocysteine was significantly higher in the study groups as compared to the controls. The median serum folate concentrations were similar in cases and controls, while the median vitamin B12 concentrations were significantly lower in the study groups compared to the controls. Low vitamin B12 concentration was associated with an approximately 2- to 3-fold increased risk for NTDs. CONCLUSION: Low maternal serum values of vitamin B12 can be considered an important etiologic factor for the development of neural tube defects in our population. This may help in both genetic counseling for families with a history of NTD malformation, and as a pre-conceptional prophylactic measure by maternal supplementation of vitamin B12 and folic acid.

Expanding the mutation and clinical spectrum of Roberts syndrome.

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.