Crisponi/CISS1 syndrome: A case series.

Crisponi/CISS1 syndrome (MIM#272430) is a rare autosomal recessive disease characterized by major feeding difficulties, camptodactyly, and anhidrosis in early childhood; and the subsequent development of paradoxical cold-induced sweating and scoliosis later in life. The syndrome is caused by biallelic mutations in CRLF1 or, much less commonly, CLCF1. Although genotype/phenotype correlation has been elusive, it has been suggested that the level of the mutant protein may correlate with the phenotypic severity. However, we show in this series of 12 patients from four families, all previously unpublished, that the homogeneity of the recently described c.983dupG (p.Ser328Argfs∗2) mutation in CRLF1 was associated with a highly variable degree of severity, and that the phenotype significantly overlaps with the recently described COG6-related anhidrosis syndrome (MIM#615328). Another fifth previously unpublished family is also described with a novel mutation in CRLF1, c.605delC (p.Ala202Valfs*32). In Saudi Arabia the prevalence of the syndrome is probably underestimated due to the difficulty in making the diagnosis considering the complex phenotype with typical neonatal and evolutive features.

Effect of consanguinity on birth defects in Saudi women: results from a nested case-control study.

BACKGROUND: The role of consanguinity in the etiology of structural birth defects outside of chromosomal and inherited disorders has always been debated. We studied the independent role of consanguinity on birth defects in Saudi women with a high prevalence of consanguineous marriages. METHODS: This case and control study was nested within a 3-year prospective cohort study to examine patterns of fetal and neonatal malformations in Saudi women at Prince Sultan Military Medical City (PSMMC), Riyadh -Saudi Arabia. Consanguineous marriages were defined as marriages with first or second cousins (related); unions beyond second cousins (distant relatives) were considered unrelated for this study. RESULTS: During the 3-year study (July 2010 through June 2013), there were 28,646 total births; of these, we included 1,179 babies with major birth defects, and 1,262 babies as their controls. The consanguinity prevalence for all included women was 49.6%. The consanguinity among babies with major Birth Defects (BDs) was 54.5% and 45.2% for controls (P < 0.0002). The prevalence of major birth defects was 41.1 per 1000 total births. Univariate analysis showed that consanguinity had a statistically significant contribution in babies born with genetic syndromes, isolated renal defects, and isolated other defects (P < 0.05). Multivariate logistic regression analyses showed that consanguinity was an independent risk factor for this high prevalence of birth defects in the study population (P < 0.0002). CONCLUSION: The prevalence of major birth defects in the study population is higher than what is reported from European countries. Consanguinity is a significant independent risk factor for the high prevalence of birth defects.

Congenital anomalies and associated risk factors in a Saudi population: a cohort study from pregnancy to age 2 years.

OBJECTIVE: To assess the three key issues for congenital anomalies (CAs) prevention and care, namely, CA prevalence, risk factor prevalence and survival, in a longitudinal cohort in Riyadh, Saudi Arabia. SETTING: Tertiary care centre, Riyadh, Saudi Arabia. PARTICIPANTS: Saudi women enrolled during pregnancy over 3 years and their 28 646 eligible pregnancy outcomes (births, stillbirths and elective terminations of pregnancy for foetal anomalies). The nested case-control study evaluated the CA risk factor profile of the underlying cohort. All CA cases (1179) and unaffected controls (1262) were followed through age 2 years. Referred mothers because of foetal anomaly and mothers who delivered outside the study centre and their pregnancy outcome were excluded. PRIMARY OUTCOME MEASURES: Prevalence and pattern of major CAs, frequency of CA-related risk factors and survival through age 2 years. RESULTS: The birth prevalence of CAs was 412/10 000 births (95% CI 388.6 to 434.9), driven mainly by congenital heart disease (148 per 10 000) (95% CI 134 to 162), renal malformations (113, 95% CI 110 to 125), neural tube defects (19, 95% CI 25.3 to 38.3) and chromosomal anomalies (27, 95% CI 21 to 33). In this study, the burden of potentially modifiable risk factors included high rates of diabetes (7.3%, OR 1.98, 95% CI 1.04 to 2.12), maternal age >40 years (7.0%, OR 2.1, 95% CI 1.35 to 3.3), consanguinity (54.5%, OR 1.5, 95% CI 1.28 to 1.81). The mortality for live births with CAs at 2 years of age was 15.8%. CONCLUSIONS: This study documented specific opportunities to improve primary prevention and care. Specifically, folic acid fortification (the neural tube defect prevalence was >3 times that theoretically achievable by optimal fortification), preconception diabetes screening and consanguinity-related counselling could have significant and broad health benefits in this cohort and arguably in the larger Saudi population.

Patterns of folic acid use in pregnant Saudi women and prevalence of neural tube defects - Results from a nested case-control study.

BACKGROUND: Although the role of folic acid (FA) in preventing neural tube defects (NTDs) is well documented, its optimal intake in pregnant women is still low in many countries. Here, we prospectively studied the prevalence of NTDs in the newborns and the patterns of FA intake in pregnant Saudi mothers. METHODS: This case-control study was nested within a 3-year project (July 2010 to June 2013) to study the patterns of birth defects in the offspring of Saudi women who received their antenatal care and delivered at Prince Sultan Military Medical City, Riyadh-Saudi Arabia. Enrolled mothers were divided into 4 groups: group 1 (FA taken before pregnancy and continued regularly after conception), group 2 (FA taken post-conception), group 3 (no FA intake), and group 4 (did not remember or were unsure of taking FA). Control mothers were randomly selected from those with normal first obstetrical ultrasound scan at 18-22 weeks of gestation. RESULTS: The cohort included 30,531 mothers giving birth to 28,646 infants. We studied 1179 mothers of babies with birth defects (BDs) and 1262 control mothers. There were 237 (9.7%) mothers in-group 1; 2001 (82%) in-group 2; 154 (6.3%) in-group 3; and 49 (2%) in-group 4. There were 49 babies with NTDs, a prevalence of 1.7/1000 total births. Among the studied mothers 2274 (93%) took FA either full or partial course. CONCLUSION: The high prevalence of NTDs and the low optimal FA intake highlight the need for a strict implementation of staple food fortification and health education program for Saudi women.