Geography of Microcephaly in the Zika Era: A Study of Newborn Distribution and Socio-environmental Indicators in Recife, Brazil, 2015-2016.

OBJECTIVES: We assessed sociodemographic and health care factors of mothers and newborns during a 2015-2016 outbreak of microcephaly in Recife, Brazil, and we analyzed the spatial distribution and incidence risk of newborns with microcephaly in relation to socio-environmental indicators. METHODS: We collected data from August 2015 through May 2016 from Brazil's Live Birth Information System and Bulletin of Microcephaly Notification, and we geocoded the data by maternal residence. We constructed thematic maps of districts, according to socio-environmental and vector indicators. We identified spatial aggregates of newborns with microcephaly by using the Bernoulli model. We performed logistic regression analyses to compare the incidence risk of microcephaly within socio-environmental indicator groups. RESULTS: We geocoded 17 990 of 19 554 (92.0%) live births in Recife, of which 202 (1.1%) newborns were classified as having microcephaly, based on a head circumference of ≥2 standard deviations below the mean. Larger proportions of newborns with microcephaly (compared with newborns without microcephaly) were born to mothers who delivered in a public hospital, did not attend college, were aged ≤19, or were black or mixed race. A higher risk of microcephaly (incidence rate ratio [IRR] = 3.90; 95% confidence interval [CI], 1.88-8.06) occurred in districts with the lowest (vs highest) Municipal Human Development Index (ie, an index that assesses longevity, education, and income). The risk of microcephaly was significantly higher where rates of larvae density (IRR = 2.31; 95% CI, 1.19-4.50) and larvae detection (IRR = 2.04; 95% CI, 1.05-4.00) were higher and rates of sewage system (IRR = 2.20; 95% CI, 1.16-4.18) and garbage collection (IRR = 1.96; 95% CI, 0.99-3.88) were lower. Newborns with microcephaly lived predominantly in the poorest areas and in a high-risk cluster (relative risk = 1.89, P = .01) in the north. CONCLUSIONS: The disproportionate incidence of microcephaly in newborns in poor areas of Recife reinforces the need for government and public health authorities to formulate policies that promote social equity and support for families and their children with microcephaly.

Ethnic and population differences in the genetic predisposition to human obesity.

Obesity rates have escalated to the point of a global pandemic with varying prevalence across ethnic groups. These differences are partially explained by lifestyle factors in addition to genetic predisposition to obesity. This review provides a comprehensive examination of the ethnic differences in the genetic architecture of obesity. Using examples from evolution, heritability, admixture, monogenic and polygenic studies of obesity, we provide explanations for ethnic differences in the prevalence of obesity. The debate over definitions of race and ethnicity, the advantages and limitations of multi-ethnic studies and future directions of research are also discussed. Multi-ethnic studies have great potential to provide a better understanding of ethnic differences in the prevalence of obesity that may result in more targeted and personalized obesity treatments.

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BACKGROUND: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits. METHODS: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations. RESULTS: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population. CONCLUSION: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup.

Clinical variability of genetic isolates of Cohen syndrome.

Cohen syndrome (CS) (OMIM#216550) is an uncommon autosomal recessive developmental disorder that has been attributed to mutations in the COH1 gene in at least 200 patients of diverse ethnic background so far. The clinical heterogeneity of CS is evident when comparing patients of different ethnic backgrounds, especially when evaluating specific system phenotypes separately, such as the ophthalmic and central nervous systems. We reviewed the available clinical data on CS cohorts of patients who share a founder effect and demonstrated that most features associated so far with CS are less than those always present in the patients who share a founder mutation thus representing clinical heterogeneity. Furthermore, there is a wide clinical variability of CS in the distinct founder mutation cohorts, the Finnish, Greek/Mediterranean, Amish and Irish travelers. The Greek/Mediterranean founder mutation is correlated to a CS phenotype characterized by specific and persistent skeletal features, corneal changes, periodontal disease, a distinct neurocognitive phenotype for the high recurrence of autism and non-verbal communication and inconstant microcephaly.

Oro-facial-digital syndrome IX with severe microcephaly: a new variant in a genetically isolated population.

We describe four patients, two pairs of siblings, with a somewhat unique oro-facial-digital syndrome. The siblings come from the Navajo population which has undergone several genetic "bottlenecks." Thus, as would be anticipated, this syndrome seems to show autosomal recessive inheritance. The combination of the presence of retinal colobomata and the paucity of digital findings in these patients leads us to believe that their condition is best described as a variant of oro-facial-digital syndrome IX. In addition to retinal colobomata, these patients also show severe microcephaly, mental retardation and short stature.

Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen syndrome.

Cohen syndrome is a rare autosomal recessive disorder with a variable clinical picture mainly characterized by developmental delay, mental retardation, microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy, severe myopia, and intermittent neutropenia. A Cohen syndrome locus was mapped to chromosome 8q22 in Finnish patients, and, recently, mutations in the gene COH1 were reported in patients with Cohen syndrome from Finland and other parts of northern and western Europe. Here, we describe clinical and molecular findings in 20 patients with Cohen syndrome from 12 families, originating from Brazil, Germany, Lebanon, Oman, Poland, and Turkey. All patients were homozygous or compound heterozygous for mutations in COH1. We identified a total of 17 novel mutations, mostly resulting in premature termination codons. The clinical presentation was highly variable. Developmental delay of varying degree, early-onset myopia, joint laxity, and facial dysmorphism were the only features present in all patients; however, retinopathy at school age, microcephaly, and neutropenia are not requisite symptoms of Cohen syndrome. The identification of novel mutations in COH1 in an ethnically diverse group of patients demonstrates extensive allelic heterogeneity and explains the intriguing clinical variability in Cohen syndrome.

Bowen-Conradi syndrome in an Indian infant: first non Hutterite case.

An Indian male infant with the lethal Bowen Conradi syndrome is described. This is the first case in the literature who is not from the Hutterite population.

Micro syndrome in Muslim Pakistan children.

OBJECTIVE: To date, Micro syndrome has been reported in only three children from one family. We describe an additional 14 children from 11 families. DESIGN: Retrospective case series. PARTICIPANTS: Fourteen children from 11 families attending one of five British hospitals. MAIN OUTCOME MEASURES: The following features were documented: pre- and postoperative eye findings, electrophysiologic analysis, systemic abnormalities, development, neuroimaging, genealogy, geographic origin of family. RESULTS: We expand and modify the description of ocular and electrophysiologic findings in Micro syndrome. The eye findings of microphakia, microphthalmos, characteristic lens opacity, and atonic pupils were the presenting feature in all infants and were the most reliable diagnostic signs in the immediate postnatal period. Cortical visual impairment, microcephaly, and developmental delay were not always detectable initially; they developed in all children by 6 months of age. Microgenitalia were a useful diagnostic clue in affected males only. Therefore, eye features were more consistently useful in determining diagnosis than dysmorphology or brain imaging. The families of all the children originate from the Muslim population of Northern Pakistan. Inheritance is likely to be autosomal recessive. CONCLUSIONS: Micro syndrome usually presents to the ophthalmologist, who may be able to make the diagnosis on the basis of characteristic eye findings combined with ethnic origin. Initially, the nature and severity of nonophthalmic features are not apparent. Early diagnosis of the underlying condition is important to guide management of the cataracts, glaucoma, and developmental delay. It is helpful for the family and medical staff to be aware of the low level of vision that develops despite optimal ophthalmic intervention. Genetic counseling extending into the wider family is particularly important in view of the high rate of consanguinity.

Malnutrition and microcephaly in Australian aboriginal children.

OBJECTIVE: To examine the association between malnutrition and microcephaly in the first two years of life. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Royal Darwin Hospital (a tertiary referral centre); 157 of 165 previously studied Aboriginal children aged under two years who were admitted with diarrhoea between May 1990 and April 1991. Birth weight, birth length, birth head circumference, admission head circumference and admission nutritional status were examined. Nutritional status was categorised according to World Health Organization (WHO) criteria for wasting (thinness) and stunting (shortness). Microcephaly on admission was defined as a head circumference less than the second percentile on Australian reference charts. Small-for-gestational-age (SGA) and birth microcephaly were defined as being less than the tenth percentile for an Australian hospitalised population, corrected for gestational age at confinement. Low birth weight (LBW) was defined as less than 2500 g. MAIN OUTCOME MEASURE: Microcephaly on admission. RESULTS: Of the 157 children, 76 (48%) were wasted, 36 (23%) stunted and 37 (24%) microcephalic on admission. A total of 26 (17%) children had been of LBW, 17 (11%) SGA and 21 (13%) microcephalic at birth. On univariate analysis, microcephaly on admission was associated with wasting (crude odds ratio [OR], 3.91; 95% confidence interval [CI], 1.6-9.7; P < 0.005), but not stunting. There were no significant associations between microcephaly on admission and LBW, being SGA, microcephaly at birth, age or sex. With multivariate analysis, birth head circumference was significantly associated with microcephaly on admission (adjusted OR, 3.62; 95% CI, 1.28-10.23; P < 0.05), as was wasting (adjusted OR, 4.38; 95% CI, 1.88-10.20; P < 0.001). CONCLUSIONS: Wasting was significantly associated with microcephaly, independent of intrauterine growth retardation (as measured by being SGA) and LBW. As malnutrition in critical periods of both intra- and extrauterine development may have irreversible effects on intellectual potential and behaviour, the emphasis on improved nutrition must begin during pregnancy, and should continue in infancy and early childhood.

[Neuroectodermal dysplasia in 2 Uzbek families]. / Sindrom neiroektodermal'noi displazii v dvukh Uzbekskikh sem'iakh.

The authors present the clinical and genealogical description of 6 patients with neuroectodermal dysplasia diagnosed by a medical expedition party in Khankin district of the Khorezm region. Unique combination of clinical signs (total alopecia, microcephalia, oligophrenia, hyperhydrosis and hypogenitalism) helped differentiating the syndrome from other well-known hereditary neuroectodermal dysplasias. The nature of the syndrome segregation in the families suggested its autosomal-recessive mode of inheritance.