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Microcephaly

Microcephaly is a rare neurological birth defect characterized by an abnormally small head size, where the brain has not developed properly during pregnancy or has stopped growing after birth, resulting in a head circumference more than two standard deviations below the mean for gestational age, sex, and ethnicity.^[1]^[2]^[3] The condition can range from mild, where individuals may have normal intelligence and lifespan, to severe, which often leads to profound intellectual disability, developmental delays, and life-threatening complications.^[1]^[2] It affects approximately 1 in 1,150 babies born in the United States, though global incidence varies based on environmental and genetic factors.^[1] The primary causes of microcephaly are diverse and often multifactorial, including prenatal infections such as Zika virus, rubella, cytomegalovirus, or toxoplasmosis, which can disrupt fetal brain development.^[1]^[2]^[3] Genetic conditions like Down syndrome or other chromosomal abnormalities, as well as craniosynostosis—a premature fusion of skull bones—can also lead to restricted brain growth.^[2] Environmental risk factors during pregnancy, such as maternal malnutrition, uncontrolled phenylketonuria (PKU), exposure to alcohol, tobacco, or harmful substances, and complications like severe hypoxia or reduced blood supply to the fetus, further contribute to the disorder.^[1]^[2] In many cases, the exact cause remains unknown, highlighting the complexity of brain development.^[1] Symptoms of microcephaly typically manifest as a noticeably smaller head at birth or become evident during routine well-baby examinations, often accompanied by a sloping forehead in severe instances.^[2]^[3] Affected individuals may experience a range of neurological and developmental issues, including seizures, poor coordination and balance, feeding difficulties, vision or hearing impairments, and significant delays in motor skills, speech, and cognitive function.^[1]^[2] Complications can extend to facial distortions, hyperactivity, and increased susceptibility to infections, with outcomes varying widely based on the underlying cause and severity.^[2] Diagnosis involves measuring head circumference using standardized growth charts from the CDC or WHO, often starting prenatally via ultrasound in the late second or early third trimester, and confirmed postnatally through physical exams and family history review.^[1]^[4]^[3] Additional tests, such as MRI, CT scans, or genetic blood work, may be used to identify specific causes, particularly if developmental delays are observed.^[4] There is no cure for microcephaly, and treatment focuses on managing symptoms and supporting development through early intervention programs, including physical, occupational, and speech therapies.^[1]^[4] In cases linked to craniosynostosis, surgery may help relieve pressure on the brain, while medications can control seizures or other complications.^[4] Prevention strategies emphasize avoiding infections like Zika during pregnancy, maintaining proper nutrition, and abstaining from alcohol and drugs.^[1]^[3]

Clinical Presentation

Signs and Symptoms

Microcephaly is defined as an occipitofrontal head circumference (OFC) more than two standard deviations below the mean for gestational age, sex, and population standards at birth or during postnatal development.^[5] The primary observable sign is a significantly reduced head size, which is typically measured using standardized growth charts such as those from the CDC or WHO to compare against age- and sex-matched norms.^[1]^[2] In addition to the small head, affected individuals may exhibit associated physical features, particularly in severe cases, including facial dysmorphisms such as a sloping forehead, prominent or low-set ears, and an underdeveloped jaw (micrognathia).^[2] These features contribute to a distinctive appearance but vary widely among cases. Developmental symptoms are common and often profound, encompassing intellectual disability, delayed motor milestones (such as inability to sit unsupported by 8 months or walk independently by 18 months), seizures, and impairments in vision or hearing.^[1]^[5] Affected children may also experience feeding difficulties, poor coordination and balance, and hyperactivity.^[2] The presentation varies by severity: mild microcephaly (OFC between 2 and 3 standard deviations below the mean) may involve only subtle developmental delays with relatively preserved function, whereas severe cases (more than 3 standard deviations below the mean) are associated with profound intellectual disability and multiple physical challenges.^[5]^[1] Age-specific manifestations differ, with neonatal presentations typically showing a small head at birth detectable via routine measurements, while symptoms in infancy and early childhood emerge progressively as delays in achieving milestones become evident.^[1]^[2]

Diagnosis

Diagnosis of microcephaly relies on standardized measurements of head circumference, typically using growth charts from the World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC). Primary microcephaly is generally confirmed when the occipitofrontal circumference (OFC) is more than 2 standard deviations (SD) below the mean for gestational age, sex, and ethnicity at birth, while severe cases are defined as more than 3 SD below the mean.^[6]^[7] Serial postnatal measurements are essential to distinguish primary microcephaly, where the head size tracks along a lower growth curve, from secondary microcephaly, where the OFC progressively falls off the growth curve due to postnatal insults.^[8] Prenatal diagnosis is often suspected through fetal ultrasound, which measures biparietal diameter or head circumference that is reduced by at least 2 SD below the mean for gestational age, prompting further evaluation.^[9] Magnetic resonance imaging (MRI) of the fetus may be employed to confirm brain anomalies, such as simplified gyral patterns or reduced brain volume, providing additional diagnostic clarity when ultrasound findings are equivocal.^[10] Postnatally, evaluation includes thorough physical examination, serial OFC measurements, and neuroimaging with computed tomography (CT) or MRI to assess brain structure, volume, and cortical malformations.^[11] Genetic testing, such as chromosomal microarray analysis (CMA) or whole-exome sequencing (WES), is recommended to identify underlying genetic causes, particularly in cases without evident environmental exposures.^[12] Differential diagnosis involves distinguishing microcephaly from conditions like craniosynostosis, which causes abnormal head shape due to premature skull suture fusion, through clinical examination and skull radiographs or CT.^[13] Nutritional deficiencies or metabolic disorders, such as hypothyroidism or organic acidemias, are ruled out via laboratory tests including serum electrolytes, thyroid function, and metabolic screening.^[11] A multidisciplinary approach, involving pediatricians, neurologists, and geneticists, ensures comprehensive assessment, including family history review and targeted investigations based on clinical suspicion.^[14] Challenges in diagnosis include variability in head shape, which can affect accurate OFC measurement, and ethnic differences in normative head circumference, where applying WHO standards may lead to overdiagnosis of microcephaly in certain populations like those of Indian or some Asian descent.^[15]^[16]

Etiology

Genetic Causes

Microcephaly can arise from genetic factors, including inherited mutations and de novo variants that disrupt normal brain development during fetal growth. Primary microcephaly, also known as autosomal recessive primary microcephaly (MCPH), represents a non-syndromic form characterized by reduced head circumference at birth and intellectual disability without additional malformations. This condition is primarily caused by biallelic mutations in genes that regulate neurogenesis, particularly those involved in centrosome integrity and cell division.^[17] Key genes associated with primary microcephaly include MCPH1 (encoding microcephalin), WDR62 (MCPH2 locus), and ASPM (MCPH5 locus). Mutations in ASPM are the most frequent, accounting for approximately 50-70% of cases, while WDR62 variants contribute to 15-20%, and MCPH1 to about 8%. These genes encode proteins localized to the centrosome and mitotic spindle, essential for proper cell cycle progression in neuronal progenitors. Over 30 genes have been implicated in MCPH, with pathogenic variants in more than 100 genes reported across primary forms. Recent studies as of 2025 have identified additional genes, such as EXOSC10, CDK4, and CETN3, further expanding the genetic heterogeneity of primary microcephaly.^[18]^[19]^[17]^[20]^[21]^[22] Syndromic forms of genetic microcephaly occur in association with multisystem disorders, such as Seckel syndrome and Rubinstein-Taybi syndrome. Seckel syndrome, characterized by severe intrauterine growth restriction, proportionate short stature, and a bird-like facial appearance, results from mutations in genes like ATR, which is involved in DNA damage response and cell cycle checkpoints. Rubinstein-Taybi syndrome features microcephaly alongside broad thumbs and toes, distinctive facial traits, and intellectual disability, primarily due to heterozygous mutations in CREBBP or EP300, which encode histone acetyltransferases critical for transcriptional regulation. These syndromes highlight how genetic disruptions beyond isolated brain development can manifest with microcephaly as a prominent feature.^[23]^[24]^[25] De novo mutations, occurring spontaneously in the affected individual rather than inherited, play a significant role in sporadic cases of microcephaly, particularly in dominant or X-linked forms. Next-generation sequencing has identified such variants in genes like POGZ and ASXL3, leading to severe developmental delay and microcephaly without family history. These mutations are increasingly detected in cohorts where traditional linkage analysis is not feasible, aiding diagnosis in non-consanguineous families.^[26]^[27] Inheritance patterns for primary microcephaly are predominantly autosomal recessive, with higher prevalence in consanguineous populations due to increased homozygosity. In Pakistani families, where consanguinity rates exceed 60%, mutations in MCPH genes like ASPM and WDR62 are notably common, contributing to carrier frequencies that elevate risk in these groups. Autosomal dominant forms, though rarer, have been reported but do not involve WDR62.^[18]^[28]^[29] Genetic causes account for approximately 25-30% of isolated microcephaly cases, with primary forms comprising a subset where no other anomalies are present. This proportion varies by population and diagnostic methods, but underscores the importance of genetic testing in etiology determination.^[30]^[31] At the molecular level, mutations in MCPH genes disrupt centrosome function and mitotic spindle orientation, leading to premature neuronal differentiation and reduced progenitor proliferation. For instance, ASPM variants impair spindle pole organization, causing asymmetric cell divisions that deplete the neuronal progenitor pool. Similarly, WDR62 mutations affect microtubule nucleation and centrosomal attachment to the spindle, resulting in disorganized cortical layering and smaller brain size. These defects primarily occur during early neurogenesis, highlighting the sensitivity of cerebral cortex expansion to genetic perturbations in cell division machinery.^[32]^[33]^[34]

Environmental and Infectious Causes

Environmental and infectious causes of microcephaly encompass a range of prenatal, perinatal, and postnatal exposures that disrupt fetal or early childhood brain development, leading to reduced head circumference and impaired neuronal growth. These factors are distinct from genetic etiologies and often involve modifiable risks such as maternal substance use or preventable infections. Teratogenic exposures during critical periods of gestation can interfere with neural progenitor proliferation and migration, resulting in congenital microcephaly.^[5] Maternal alcohol consumption during pregnancy is a well-established teratogen associated with fetal alcohol spectrum disorders (FASD), which frequently include microcephaly as a hallmark feature due to disrupted brain volume and head growth. Prenatal alcohol exposure has been shown to increase the rates of microcephaly, with affected children exhibiting smaller head circumferences compared to unexposed peers. Similarly, maternal tobacco smoking during pregnancy is linked to reduced fetal head circumference and an elevated risk of congenital microcephaly, likely through vascular effects and nicotine-induced growth restriction. Ionizing radiation exposure in utero, particularly during the first trimester, is a potent teratogen that commonly causes microcephaly, as evidenced by historical cohorts from atomic bomb survivors and medical imaging studies, where doses above 50 mGy significantly impair brain development. Antiepileptic drugs like valproic acid, when used in early pregnancy, heighten the risk of fetal microcephaly and craniofacial dysmorphisms by altering neural tube closure and progenitor cell function.^[35]^[36]^[37]^[38]^[39] Nutritional deficiencies in the mother or infant can also precipitate microcephaly by hindering essential processes like neuronal migration and myelination. Severe maternal iodine deficiency during pregnancy leads to endemic cretinism, characterized by microcephaly and irreversible neurological impairment, with studies showing a reduction in microcephaly rates from 27% to 11% following iodine supplementation in deficient populations. Folate deficiency in utero has been associated with microcephaly alongside neural tube defects, as inadequate folate impairs DNA synthesis and cerebral folate transport, contributing to abnormal brain morphogenesis.^[40]^[41] Infectious agents represent a major category of acquired causes, particularly congenital infections that cross the placenta and target developing neural tissues. The TORCH complex—encompassing toxoplasmosis, other agents (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus (CMV), and herpes simplex virus—is a primary culprit, with CMV being the most frequent, where microcephaly occurs in up to 20% of symptomatic congenital CMV cases, through direct viral cytopathy in neural progenitors.^[5] Zika virus, an arbovirus, gained prominence for inducing severe microcephaly during the 2015-2016 outbreaks, where maternal infection interfered with cortical development, leading to head circumferences reduced by over 3 standard deviations in affected infants. Other arboviruses, such as chikungunya, have been linked to congenital microcephaly in case reports from endemic regions, with maternal infection during pregnancy correlating with smaller head sizes at birth.^[5]^[42] Hypoxic-ischemic events, including perinatal asphyxia and placental insufficiency, can result in acquired microcephaly by compromising oxygen delivery to the fetal brain, leading to neuronal loss and volume reduction. Placental pathology, such as infarction or thrombosis, has been associated with increased microcephaly risk, as these disrupt nutrient and oxygen transfer during gestation.^[43]^[44] Postnatal causes primarily arise from environmental toxins or metabolic disruptions in early infancy. Severe malnutrition after birth can stunt head growth, contributing to progressive microcephaly, especially in resource-limited settings where caloric and nutrient deficits persist. Lead poisoning in young children impairs neurodevelopment and has been implicated in reduced brain volume, potentially leading to microcephaly-like features through heavy metal toxicity. Untreated congenital hypothyroidism, if not screened and managed early, results in microcephaly due to thyroid hormone deficiency affecting brain maturation.^[1]^[45]^[46] Certain risk factors amplify susceptibility to these causes. Advanced maternal age over 35 years may slightly elevate microcephaly risk through increased chromosomal instability or vascular complications, though evidence is mixed. Lower socioeconomic status correlates with higher incidence, driven by limited access to prenatal care, higher exposure to infections like Zika, and nutritional inadequacies, with studies showing up to 30% greater odds in low-education households. Geographic hotspots, such as Latin America during Zika epidemics, highlight how vector-borne diseases exacerbate risks in vulnerable populations.^[44]^[47]^[47] The link between Zika virus and microcephaly was formally recognized in historical context following the 2015 outbreak in Brazil, where cases surged dramatically; the World Health Organization declared it a Public Health Emergency of International Concern in February 2016, prompting global surveillance and research into prevention. This event underscored the role of emerging infections in non-genetic microcephaly etiologies.^[48]

Pathophysiology

Mechanisms of Brain Development Impairment

Microcephaly arises from disruptions in the early phases of neurogenesis, particularly during the proliferation of neural stem cells in the ventricular zone between gestational weeks 8 and 24, when the cerebral cortex expands rapidly.^[49] This period is critical for generating the neuronal progenitor pool, and impairments lead to a depleted population of neural precursors, resulting in fewer neurons overall.^[49] Key cellular processes affected include the balance between symmetric and asymmetric cell divisions of neural progenitors, which normally expands the progenitor pool while producing differentiated neurons; in microcephaly, this balance shifts toward depletion, yielding a smaller cerebral cortex.^[49] Additionally, dysregulation of apoptosis contributes to excessive neuronal loss, further reducing cortical volume.^[49] These disruptions culminate in structural abnormalities such as simplified gyral patterns, including pachygyria or agyria, diminished white matter, and ventriculomegaly, which are detectable via MRI and reflect the underlying failure in cortical layering and expansion.^[49] Across diverse etiologies, these impairments converge on common pathways involving microtubule dynamics and centrosome integrity, which are essential for proper spindle assembly and chromosome segregation during mitosis.^[49] For instance, genetic mutations, environmental toxins, or viral infections like Zika—where the NS5 protein localizes to centrosomes and inhibits cell cycle progression—prolong mitosis and activate surveillance mechanisms that trigger progenitor cell death, independent of the specific cause.^[49]^[50] Prenatal insults during this gestational window are most severe, as they coincide with peak cortical neurogenesis, whereas postnatal disruptions typically result in milder, secondary effects on brain growth.^[49] Insights from animal models, such as mouse knockouts of genes implicated in microcephaly, demonstrate these mechanisms through significant brain size reductions of 30-50%, mirroring the progenitor depletion and cortical thinning observed in humans.^[51]^[49] These models highlight how early embryonic disruptions in cell division and survival propagate to lifelong neurodevelopmental deficits.^[52]

Associated Neurological Features

Microcephaly is frequently accompanied by cortical malformations such as lissencephaly, characterized by a smooth brain surface due to disrupted neuronal migration, and polymicrogyria, involving excessive small gyri that impair cortical connectivity and cognitive function.^[53]^[54]^[55] These anomalies arise from defects in neurogenesis or neuronal organization, leading to disorganized layering and reduced functional integration across brain regions.^[56] Cerebellar and brainstem hypoplasia are common secondary features, often resulting in impaired motor coordination and difficulties with feeding due to disrupted swallowing reflexes and postural control.^[57]^[58] In conditions like microcephaly with pontine and cerebellar hypoplasia, these structural deficits manifest as ataxia and oral-motor incoordination, exacerbating early developmental challenges.^[59]^[60] White matter abnormalities, including periventricular leukomalacia and ventriculomegaly, further contribute to neurological compromise by reducing myelinated tracts and causing compression of adjacent tissue from enlarged ventricles.^[61]^[62] These changes, observed in both infectious and genetic forms, lead to diminished signal transmission and increased susceptibility to injury.^[63] Functionally, up to 40% of individuals with microcephaly experience epilepsy, often with characteristic EEG patterns such as hypsarrhythmia in infantile spasms, alongside spasticity from upper motor neuron involvement and sensory processing disorders affecting integration of visual or auditory inputs.^[64]^[65]^[66] Spasticity typically presents as mild to moderate hypertonia, while sensory issues contribute to behavioral and adaptive deficits.^[17] The associated features exhibit significant heterogeneity depending on etiology; for instance, congenital cytomegalovirus infections often involve intracranial calcifications and white matter hyperintensities, whereas genetic forms like autosomal recessive primary microcephaly feature a thin cortex with simplified gyral patterns.^[67]^[68] This variation underscores the diverse impacts on brain architecture across causes.^[69] Advanced imaging techniques, such as diffusion tensor imaging, reveal altered neural tracts in microcephaly, showing reduced fractional anisotropy and disrupted fiber integrity in white matter pathways like the corpus callosum.^[70]^[71] These findings, detectable via MRI, highlight microstructural deficits beyond gross anatomy.^[72]

Management and Prognosis

Treatment Approaches

There is no cure for microcephaly, and treatment focuses on symptomatic and supportive management to address associated complications and optimize quality of life rather than reversing the underlying brain size reduction.^[1] Management is tailored to the severity and etiology, emphasizing early detection of comorbidities such as seizures, developmental delays, and motor impairments.^[73] Pharmacological interventions primarily target seizure control, as epilepsy affects a significant proportion of individuals with microcephaly, particularly in congenital Zika virus-associated cases where up to 86% may require antiepileptic drugs (AEDs). Levetiracetam is commonly used as an adjunctive therapy in pediatric refractory epilepsy, including in children with microcephaly, due to its favorable safety profile and efficacy in reducing seizure frequency by at least 50% in over 50% of cases with partial seizures.^[74]^[75] Growth hormone therapy has been trialed in select cases of mild, sporadic primary microcephaly with associated short stature, showing improved linear growth and head circumference in small cohorts, though evidence remains limited to case series without broad clinical endorsement.^[76] In neonates with microcephaly linked to congenital infections or metabolic issues, treatment of hyperbilirubinemia via intensive phototherapy or exchange transfusion is essential to prevent kernicterus-related neurological worsening. Surgical options are reserved for specific complications; ventriculoperitoneal shunt placement may be indicated in rare instances of co-occurring hydrocephalus, as seen in the "microcephalic hydrocephalus" paradox where excess cerebrospinal fluid accumulation exacerbates intracranial pressure despite small head size.^[61] For severe craniofacial dysmorphisms, such as those in syndromic microcephaly with craniosynostosis, reconstructive craniofacial surgery can alleviate functional issues like airway obstruction or elevated intracranial pressure.^[77] Emerging therapies for monogenic forms, such as those involving MCPH1 mutations, include preclinical gene editing research using CRISPR-Cas9 in induced pluripotent stem cell-derived brain organoids, which recapitulate microcephaly phenotypes and suggest potential for correcting neural progenitor defects, though no clinical trials are available as of 2025. Stem cell approaches, including neural progenitor transplantation to promote neurogenesis, remain in preclinical stages, with studies demonstrating disrupted stem cell proliferation in microcephaly models but lacking human trial data.^[78]^[22] A multidisciplinary team approach is central, involving physical therapy to enhance motor skills, occupational therapy for daily functioning, and speech therapy to support communication in cases of cognitive and developmental delays. The American Academy of Pediatrics (AAP) recommends immediate referral to early intervention programs for children with microcephaly to maximize neurodevelopmental outcomes through coordinated therapies.^[73]^[79] The World Health Organization (WHO) endorses similar early intervention strategies within broader congenital anomaly management frameworks to address long-term disabilities.

Long-term Outcomes

The long-term developmental outcomes for individuals with microcephaly vary widely depending on the severity and underlying etiology, but intellectual disability is a common feature across cases. In milder forms, such as certain genetic primary microcephaly, full-scale IQ scores typically range from 40 to 70, with an average around 52, allowing for some functional abilities despite delays.^[80] Severe cases, particularly those associated with congenital infections, often result in profound cognitive impairment, with standardized scores at or near the floor of 55 and developmental ages equivalent to 2-4 months by age 2-3 years.^[81] Most individuals require lifelong support for daily activities, as microcephaly is a permanent condition without curative treatment, though a minority with isolated mild microcephaly may achieve near-normal cognitive function.^[5]^[82] Comorbidities significantly influence prognosis, with increased risks of neurological issues such as epilepsy (affecting up to 81% in some cohorts), visual impairments (moderate to severe in about 48%), and behavioral challenges including autism spectrum traits and stereotypic behaviors.^[81]^[83]^[84] Early mortality is elevated, particularly from complications like aspiration pneumonia due to dysphagia and poor protective reflexes, which are prevalent in severe congenital forms.^[85] Quality of life is impacted by the need for educational accommodations, such as individualized learning plans to address cognitive and motor delays, and substantial employment challenges, with most adults facing limited independence due to intellectual disability.^[83] Family burden is high, with caregivers reporting drastic life changes, anxiety, and reduced personal quality of life from ongoing care demands.^[86] Early intervention therapies have shown potential to mitigate some effects, improving neurodevelopmental trajectories and alleviating family stress through better child outcomes.^[87]^[88] Outcomes differ markedly by etiology, with congenital microcephaly—especially from intrauterine infections like Zika—linked to more profound disability and lower independence compared to postnatal acquired forms, where prompt treatment of causes (e.g., metabolic disorders) can yield better prognosis.^[5]^[89] In Zika-related cases, nearly all children exhibit severe impairments across domains.^[81] Longitudinal cohort studies, such as the Microcephaly Epidemic Research Group Paediatric Cohort following over 700 children for up to several years, indicate variable progress, with 20-40% achieving partial independence in basic self-care depending on early comorbidities and support.^[90] Recent 2020s research highlights neuroplasticity in young children with microcephaly, suggesting targeted cognitive stimulation and intensive therapies may foster modest gains in developmental skills, particularly in receptive language and motor function.^[91]^[92]

Epidemiology and History

Prevalence and Risk Factors

Microcephaly occurs globally with a baseline prevalence estimated at 2 to 12 cases per 10,000 live births, though rates vary significantly by region and population characteristics.^[93]^[94] In high-income countries like the United States and Europe, prevalence typically ranges from 1.5 to 8.7 per 10,000 live births, while in low-resource settings, rates can be higher due to limited prenatal care and higher burdens of infectious diseases.^[93]^[94] For instance, during non-epidemic periods in Brazil, prevalence has been reported at approximately 4.4 per 10,000 live births.^[95] In consanguineous populations, such as those in parts of South Asia and the Middle East, the prevalence of genetic forms of microcephaly is elevated, reaching up to 1 in 10,000 births compared to lower rates in non-consanguineous groups.^[96] This increase is attributed to autosomal recessive inheritance patterns, with consanguinity conferring an odds ratio of 3.1 for neural-only microcephaly.^[97] Epidemiological trends show stability in baseline genetic cases over time, but infectious outbreaks have caused temporary spikes; notably, during the 2015–2016 Zika virus epidemic in Brazil, prevalence surged to 1.5 to 5 cases per 1,000 live births in affected regions like Paraíba state.^[98]^[99] Key modifiable risk factors include maternal infections, particularly Zika virus, where seroprevalence during pregnancy correlates with elevated microcephaly rates.^[99] Consanguinity increases risk for recessive genetic forms with odds ratios ranging from 2 to 10, advanced maternal age is associated with higher overall congenital anomaly risks including microcephaly, and socioeconomic disparities exacerbate vulnerability through poorer access to healthcare and higher exposure to environmental hazards.^[97]^[100]^[101] Geographically, genetic microcephaly predominates in South Asia and the Middle East due to higher consanguinity rates, while infectious causes, especially post-2015 Zika outbreaks, have driven elevated incidence in the Americas.^[102]^[103] Surveillance efforts by the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) track these patterns through population-based systems, though underreporting remains prevalent in developing countries, potentially underestimating true burdens by up to 50% in regions like Latin America.^[104]^[105]^[106] As of 2025, Zika-related microcephaly cases have declined globally following the 2016 peak, attributed to reduced transmission and emerging vaccine candidates, though baseline infectious risks persist. Sporadic Zika outbreaks occurred in Asia in 2024, maintaining low-level transmission risks.^[107]^[48] Concurrently, awareness of cytomegalovirus (CMV) screening during pregnancy is increasing, as CMV represents a leading preventable infectious cause of microcephaly in non-Zika contexts. In the U.S., congenital CMV newborn screening has been implemented in additional states, including Connecticut as of July 2025, enhancing early detection of this preventable cause.^[108]^[109]

Historical Developments and Notable Cases

The medical recognition of microcephaly dates back to the 19th century, when German pathologist Rudolf Virchow described cases of reduced cranial capacity accompanied by intellectual impairment, coining the term "microcephalic idiocy" in his 1867 autopsy reports on affected individuals.^[83] By the 1930s, clinicians began classifying microcephaly into primary (congenital, genetic forms present at birth without progressive degeneration) and secondary (acquired postnatally due to environmental factors or insults) categories, a distinction that facilitated early etiological investigations.^[7] In the mid-20th century, environmental links emerged prominently; in 1941, Australian ophthalmologist Norman McAlister Gregg reported the association between maternal rubella infection during early pregnancy and congenital anomalies, including microcephaly, based on observations of 78 cases in Sydney, fundamentally altering perceptions of infectious teratogenesis. The 1960s thalidomide tragedy further illuminated iatrogenic causes, as the sedative, prescribed to pregnant women, resulted in birth defects such as microcephaly in exposed fetuses, prompting global regulatory reforms on drug safety. Modern milestones include the 2002 identification of the MCPH1 gene as the first causative locus for autosomal recessive primary microcephaly, reported by Jackson et al. in a study of consanguineous families from Pakistan and Saudi Arabia, ushering in the era of genetic dissection of the disorder.^[110] The 2015 Zika virus outbreak in Brazil marked a pivotal outbreak-related surge, with the World Health Organization declaring it a Public Health Emergency of International Concern in February 2016 due to its link to microcephaly, following reports of over 4,000 suspected cases by late 2015, which catalyzed international collaborative research.^[48]^[111] Notable historical cases include William Henry Johnson (c. 1857–1926), known as "Zip the Pinhead," an African American performer in 19th-century American freak shows whose conical head and cognitive features were attributed to microcephaly, exemplifying the era's exploitative public exhibitions of the condition.^[112] In contemporary contexts, the Brazilian Zika epidemic yielded significant cohorts, such as the 2015–2016 Pernambuco series of 13 infants with congenital Zika syndrome featuring severe microcephaly, calcifications, and arthrogryposis, which informed diagnostic criteria and long-term studies.30902-3/fulltext) Research on microcephaly evolved from 19th–20th century descriptive and epidemiological approaches to molecular genetics in the late 20th and early 21st centuries, with gene discoveries enabling insights into neurogenesis defects.^[113] By the 2020s, emphasis shifted toward prevention, including development of maternal vaccines against Zika virus to mitigate fetal transmission risks, as evidenced by preclinical trials demonstrating protective immunity.^[114] The Zika crisis also drove cultural shifts, with awareness campaigns by organizations like the WHO reducing stigma through education on supportive care and family inclusion for affected children.

References

[1]
Microcephaly | Birth Defects - CDC
Nov 21, 2024 · Microcephaly is a condition where a baby's head is much smaller than expected. During pregnancy, a baby's head grows because the baby's brain grows.
[2]
Microcephaly - Symptoms & causes - Mayo Clinic
Sometimes detected at birth, microcephaly often occurs when there is a problem with brain development in the womb or when the brain stops growing after birth.Overview · Symptoms · When to see a doctor · Causes
[3]
Microcephaly: MedlinePlus Medical Encyclopedia
### Microcephaly Summary
[4]
Microcephaly - Diagnosis & treatment - Mayo Clinic
Learn more about microcephaly, when an infant's head is smaller than expected. The condition affects child development.Missing: definition | Show results with:definition
[5]
Microcephaly - PMC - NIH
Jun 9, 2017 · Microcephaly is defined as a head circumference more than two standard deviations below the mean for gender and age.
[6]
Microcephaly Diagnostic Guidelines - Starship Hospital
Feb 22, 2021 · Microcephaly is defined here as an occipito-frontal circumference (OFC) of greater than 2 SD below the mean for age, sex and ethnicity, which is ...Microcephaly Diagnostic... · Assessment · Investigations
[7]
Congenital microcephaly: Case definition & guidelines for data ...
Physiologically, congenital microcephaly is a disorder of reduced brain size and volume resulting from abnormal fetal development. Microcephaly has been ...
[8]
Diagnostic Algorithm for Microcephaly - Pediatric Neurology Briefs
Nov 1, 2013 · Serial OFC measurements that follow the growth curve suggest a primary microcephaly, whereas an OFC that falls relative to the growth curve is ...Missing: neuroimaging | Show results with:neuroimaging
[9]
insights and difficulties in prenatal diagnosis of fetal microcephaly
Mar 11, 2024 · The prenatal investigation of suspected microcephaly should begin whenever the HC measurement is 2 SD or more below the mean for gestational age ...Abstract · Introduction · False positive diagnosis of... · False negative diagnosis of...
[10]
Prenatal diagnosis of microcephaly through combined MRI and ...
Dec 15, 2023 · Ultrasonography (US) is currently the most commonly used imaging modality for detecting microcephaly in the second trimester of pregnancy.
[11]
Microcephaly in infants and children: Etiology and evaluation
Oct 10, 2024 · The etiology and evaluation of microcephaly in infants and children will be reviewed here.
[12]
[PDF] EvALuAtIoN of thE ChILd wIth mICroCEPhALy (AN EvIdENCE ...
Recommendations are presented for neuroimaging, genetic testing, and screening for coexistent conditions. Please refer to the full guideline at www.aan.com for ...
[13]
Microcephaly Differential Diagnoses - Medscape Reference
Jan 21, 2025 · The main differential consideration is to first determine if the patient has craniosynostosis, a problem with brain growth, or no issues beyond head size.Missing: metabolic | Show results with:metabolic
[14]
[PDF] pediatric newborn medicine clinical practice guidelines
Oct 26, 2021 · Diagnosis of microcephaly is given if head circumference is less than the 3rd percentile. • Consultation with specialists like a pediatric ...
[15]
World variation in head circumference for children from birth to 5 ...
Except for Indians and some Asian neonates, adopting the WHO head circumference standards would overdiagnose macrocephaly and underdiagnose microcephaly.
[16]
insights and difficulties in prenatal diagnosis of fetal microcephaly
Mar 12, 2024 · The prenatal investigation of suspected microcephaly should begin whenever the HC measurement is 2 SD or more below the mean for gestational age ...
[17]
WDR62 Primary Microcephaly - GeneReviews® - NCBI Bookshelf
Feb 17, 2022 · To date, pathogenic variants in more than 100 genes are known to cause primary microcephaly (for review, see Jayaraman et al [2018]).
[18]
Autosomal recessive primary microcephaly (MCPH): clinical ...
Jun 13, 2011 · The ASPM gene at MCPH5 locus and WDR62 at MCPH2 locus have been found mutated in more than 55-60% of the MCPH families jointly, while CDK5RAP2 ...
[19]
Comprehensive review on the molecular genetics of autosomal ...
Aug 8, 2018 · The most common causes of MCPH are biallelic mutations in ASPM (68.6%), followed by those in the WDR62 gene (14.1%) and MCPH1 gene (8%).1. Introduction · (i) Mcph1 (microcephalin) · (ii) Mcph2 (wdr62)<|control11|><|separator|>
[20]
Microcephaly - Breda Genetics
Dec 25, 2018 · The genes of which mutations cause Seckel syndrome are: ATR, RBBP8, CENPJ, CEP152, CEP63, NIN, DNA2, TRAIP, and NSMCE2. Genetic testing strategy.
[21]
Rubinstein-Taybi Syndrome - GeneReviews® - NCBI Bookshelf
Aug 30, 2002 · This condition is caused by missense variants in the last part of exon 30 or the beginning part of exon 31 of CREBBP or the homologous regions ...Missing: Seckel | Show results with:Seckel
[22]
Rubinstein-Taybi syndrome - Genetics - MedlinePlus
Mutations in the EP300 gene cause a small percentage of cases of Rubinstein-Taybi syndrome. Like the CREBBP gene, this gene provides instructions for making a ...Missing: microcephaly Seckel
[23]
De novo POGZ mutations are associated with neurodevelopmental ...
Seven patients with similar phenotypes of developmental delay and microcephaly were found by whole-exome sequencing to have de novo loss-of-function mutations ...
[24]
De novo frameshift mutation in ASXL3 in a patient with global ...
Sep 17, 2013 · We provide additional evidence that, truncating and frameshifting mutations in the ASXL3 gene are the cause of a newly recognized disorder ...
[25]
Molecular analysis of 23 Pakistani families with autosomal recessive ...
Oct 27, 2016 · Primary microcephaly is genetically heterogeneous, with most cases showing autosomal recessive inheritance. We designed a panel containing ...
[26]
Mutations in WDR62 gene in Pakistani families with autosomal ...
Mutations in WD repeat protein 62 are associated with autosomal recessive primary microcephaly with cortical malformations.
[27]
Microcephaly, an etiopathogenic vision - ScienceDirect.com
In 2014, a study reported a genetic or presumed genetic cause in 28.5%, perinatal neurological damage in 27%, craniosynostosis in 2%, postnatal neurological ...
[28]
Primer on Microcephaly | NeoReviews - AAP Publications
Jan 1, 2017 · The top 2 reported etiologies for microcephaly in cases with a known underlying diagnosis are genetic disorders and perinatal brain damage ...
[29]
the molecular mechanisms of primary microcephaly
Many primary microcephaly mutations occur in genes that encode centrosome proteins, highlighting an important role for centrosomes in cortical development.
[30]
Same but different: pleiotropy in centrosome-related microcephaly
Mar 23, 2018 · WDR62 mutants have defective attachment of centrosomes to mitotic spindles, disorganized PCM, abnormal microtubule nucleation, and improper ...Introduction · Fewer Neurons, Smaller Brain · Cpap: Poster Boy For...
[31]
Autosomal recessive primary microcephaly (MCPH) - PubMed Central
It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation ...Do Mcph1, Wdr62 And Aspm... · Genes In Mcph · 1- Microcephalin (mcph1)
[32]
Relationships between Head Circumference, Brain Volume and ...
Feb 29, 2016 · These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure.
[33]
Maternal Smoking During Pregnancy and Offspring Head Growth in ...
Oct 12, 2021 · Maternal smoking during pregnancy is associated with reduced weight, length and head circumference of the newborn. Postnatally, these ...
[34]
Antenatal antecedents of a small head circumference at age 24 ...
Nov 2, 2010 · Tobacco exposure during pregnancy has been associated with an increased risk of congenital microcephaly [33], but we know of no studies ...
[35]
Radiation Effects on the Fetus - StatPearls - NCBI Bookshelf
Microcephaly is the most frequently seen manifestation of radiation injury in utero. Diagnostic radiology imaging is essential. It is noted that the risks to ...
[36]
Prenatal Effects of Antiepileptic Drugs - PMC - NIH
Exposure to subteratogenic doses of valproic acid can cause microcephaly and behavioral changes (i.e., deficits in spatial learning tasks and altered ...
[37]
Maternal iodine insufficiency and adverse pregnancy outcomes - PMC
In China, Cao et al. (1994) reported reduction in the rate of microcephaly from 27% to 11% with iodine repletion of pregnant women with severe iodine ...
[38]
Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention ...
Jul 28, 2022 · Intrauterine folate deficiency during pregnancy has been associated with neural tube defects ... microcephaly, epilepsy, and cerebral ...
[39]
Chikungunya virus antepartum transmission and abnormal infant ...
We found potential statistical associations between maternal CHIKV infection during pregnancy and macerated stillbirth (P = 0.006), microcephaly (P <0.001), ...<|separator|>
[40]
Early prediction of the development of microcephaly after hypoxic ...
The development of microcephaly after significant hypoxic-ischemic cerebral injury in the full-term newborn has major prognostic significance.Missing: perinatal asphyxia
[41]
Factors associated with small head circumference at birth among ...
Maternal smoking, whether before or during pregnancy, was not associated with microcephaly (Table 2). Similarly, self-reported vaginal bleeding, antepartum ...
[42]
Developmental Neuropathology of Environmental Agents - PMC
Such effects may be the result of a direct toxicity of ethanol, of inhibition of neurotrophic properties of glutamate, or of activation of GABA receptors (176).Methylmercury · Lead · Antiepileptic Drugs<|separator|>
[43]
Thyroid Hypoplasia as a Cause of Congenital Hypothyroidism ... - NIH
Thyroid Hypoplasia as a Cause of Congenital Hypothyroidism in Monozygotic Twins ... The twins had an unusual dysmorphic facialappearance with microcephaly ...
[44]
Socioeconomic risk markers of congenital Zika syndrome
Sep 29, 2022 · The odds of CZS were up to 30% higher comparing live births of women with less than 12 years of education to those with more than 12 years of education.
[45]
https://pmc.ncbi.nlm.nih.gov/articles/PMC3625636/
[46]
Time is of the essence: the molecular mechanisms of primary ...
Many primary microcephaly mutations occur in genes that encode centrosome proteins, highlighting an important role for centrosomes in cortical development.
[47]
Zika virus NS5 localizes at centrosomes during cell division - PMC
Zika virus (ZIKV) nonstructural protein 5 (NS5) plays a critical role in viral RNA replication and mediates key virus-host cell interactions.
[48]
The neurological and non-neurological roles of the ... - Frontiers
Aspm knockout ferrets showed robust microcephaly, with a reduction in brain weight of around 25–40%.
[49]
Modeling microcephaly with cerebral organoids reveals a WDR62 ...
Jun 13, 2019 · Mouse genetic studies suggested that Wdr62 deletion reduces NPCs and leads to a smaller brain size. Wdr62 mutant mice exhibit a mild ...
[50]
Malformations of Cortical Development - PMC - PubMed Central - NIH
Disorders of MT formation/function result in multiple brain abnormalities including microcephaly (impaired mitosis); lissencephaly, pachygyria, band ...
[51]
Congenital Microcephaly with a Simplified Gyral Pattern: Associated ...
The term “lissencephaly” is used to describe a cortical malformation caused by disturbed neuronal migration. The affected cortex is agyric, and as a result of ...
[52]
Malformations of cortical development: clinical features and genetic ...
The malformations of cortical development shown include severe congenital microcephaly with a PMG-like cortical malformation (A), right-sided dysplastic ...
[53]
Definitions and classification of malformations of cortical development
Aug 10, 2020 · Microcephaly may have normal or abnormal cortex and may be further classified based on the presence of associated cortical anomalies, such as ...
[54]
CASK Disorders - GeneReviews® - NCBI Bookshelf
Nov 26, 2013 · MICPCH is typically seen in females with moderate-to-severe intellectual disability, progressive microcephaly with or without ophthalmologic ...
[55]
Spectrum of pontocerebellar hypoplasia in 13 girls and boys with ...
Mar 27, 2012 · Pontocerebellar hypoplasia (PCH) is a heterogeneous group of diseases characterized by lack of development and/or early neurodegeneration of ...Cask Molecular Analysis · Table 2 · Mri FeaturesMissing: deficits | Show results with:deficits
[56]
Characteristics of Dysphagia in Infants with Microcephaly Caused by ...
Feeding problems in persons with neurologic diseases are mainly explained by brain damage leading to lack of swallowing coordination; abnormalities of posture; ...
[57]
Congenital Zika Syndrome and Disabilities of Feeding and ...
Feb 22, 2023 · Affected infants develop microcephaly and other congenital malformations referred to as congenital Zika syndrome. The neurological ...
[58]
The “microcephalic hydrocephalus” paradox as a paradigm of ...
Nov 21, 2023 · Case study of cCMV infection presenting with microcephaly, mild ventriculomegaly, white matter hyperintensities, and sensorineural abnormalities ...
[59]
Early cranial ultrasound lesions predict head circumference at age 2 ...
Feb 4, 2016 · We hypothesize that a common final pathway to microcephaly in our ELGAN Study subjects is reduced brain volume due to widespread white matter ...Results · Cranial Sonograms With No... · VentriculomegalyMissing: changes | Show results with:changes
[60]
Microcephaly in Neurometabolic Diseases - PMC - PubMed Central
Jan 11, 2022 · Symptoms are caused by the progressive deterioration of mental, motor, and perceptual functions. The authors review the diseases with ...Microcephaly In... · 2.5. Microcephaly, Amish... · 4. Congenital And Acquired...
[61]
Association of epilepsy with different groups of microcephaly - PubMed
Overall prevalence of epilepsy was 40.9%. Furthermore, there was a significantly higher prevalence of epilepsy in males. Main seizure type was generalized ...
[62]
Evaluation of the child with microcephaly (an evidence-based review)
Sep 15, 2009 · Severe microcephaly would be expected in 0.1% of children if normal distribution is assumed, which agrees with the published estimate of 0.14% ...
[63]
ASPM Primary Microcephaly - GeneReviews® - NCBI Bookshelf
Apr 2, 2020 · Syndromic PM, a heterogeneous group in which PM is associated with extracerebral anomalies and growth impairment (e.g., Rubinstein-Taybi ...
[64]
Intracranial calcifications on CT: an updated review - PMC
Congenital CMV infection is usually associated with chorioretinitis, microcephaly and IC (6). IC are the most common findings and are seen in 34–70% of ...
[65]
Microcephaly associated with abnormal gyral pattern - PubMed
Primary microcephaly is a heterogeneous group of cerebral malformations either with a relatively well-preserved or an abnormal gyral pattern.
[66]
Predictors of Neurodevelopment in Microcephaly Associated with ...
Nov 21, 2023 · The long-term outcomes of symptomatic congenital CMV infection show microcephaly in 70%, mental retardation in 61%, hearing loss in 30%, ...
[67]
Decreased Axon Caliber Underlies Loss of Fiber Tract Integrity ...
Here, we sought to elucidate the anatomical underpinnings of microcephaly in AS, reasoning that better understanding the causes of impaired brain growth in the ...
[68]
The neurological and non-neurological roles of the primary ...
Longitudinal diffusion tensor imaging revealed nerve Fiber alterations in Aspm mutated microcephaly model mice. Neuroscience 371, 325–336. doi: 10.1016/j ...
[69]
A DTI‐based tractography study of effects on brain structure ...
We used DTI‐based probabilistic tractography to identify localized regions of WM fiber bundles within three major WM classes: transcallosal tracts (CC, ...
[70]
Microcephaly | Pediatric Care Online - AAP Publications
Apr 15, 2021 · Treatment Approach. Treatment is largely supportive, with targeted therapies to address functional disabilities. Refer for early intervention ...
[71]
Endocrine Dysfunction in Children with Zika-Related Microcephaly ...
Dec 22, 2020 · About 86% of the children were taking anti-epileptic drugs (AEDs) at the time of the evaluation. These drugs can have endocrine side effects.
[72]
The efficacy and side effects of levetiracetam on refractory epilepsy ...
LEV reduced seizure frequency by at least 50% in 58.3% of patients with partial seizures, in 32.0% of patients with primary generalized seizures, and in 17.6% ...
[73]
Growth Hormone Treatment in Children With Sporadic Primary ...
Four children with sporadic primary microcephaly associated with short stature, delayed bone age, and low growth velocity are described.
[74]
Microcephaly Treatment & Management - Medscape Reference
Jan 21, 2025 · Craniosynostosis warrants consultation with a neurosurgeon and/or craniofacial surgeon, to consider surgery to treat increased intracranial ...
[75]
Advantages of CRISPR-Cas9 combined organoid model in the study ...
The results demonstrate that the combination of iPSC-derived brain organoids and CRISPR-Cas9 can exhibit microcephaly pathological features and explain the ...
[76]
CETN3 deficiency induces microcephaly by disrupting neural stem ...
Sep 9, 2025 · We showed that CETN3-knockout (KO) organoids successfully recapitulated the microcephaly phenotype of reduced size compared to the control ...
[77]
Microcephaly | Pediatrics In Review - AAP Publications
Jul 1, 2025 · Complex craniosynostosis and maternal metabolic disorders have been shown to disrupt brain development, leading to fetal microcephaly that ...
[78]
Neurological outcome in WDR62 primary microcephaly
Sep 25, 2021 · Average full-scale IQ was 51.8 (SD 12.6, range 40–70; Fig. 2c). Irrespective of the subtest assessed, we observed interindividual variability ...
[79]
Developmental Outcomes Among Young Children With Congenital ...
May 5, 2020 · Almost all children (118 [97.5%]) scored at the standard score floor of 55 on the cognitive domain, with mean score of 55.3 and minimal ...
[80]
Microcephaly: Symptoms, Causes & Outlook - Cleveland Clinic
Microcephaly occurs when your baby's head is smaller than expected. Abnormal brain development can cause microcephaly.Missing: differential | Show results with:differential
[81]
Microcephaly - MedLink Neurology
Neurologic abnormalities, such as hypotonia, spasticity, seizures, ataxia, tremor, developmental delay, and intellectual disability, may accompany microcephaly.
[82]
Microcephaly (Concept Id: C4551563) - NCBI
The facial features may include microcephaly or trigonocephaly / prominent (but not fused) metopic ridge, hypotonic facies with full cheeks, synophrys ...
[83]
Early Life Epilepsies are a Comorbidity of Developmental Brain ...
Other factors often seen in general, are nonseizure-related aspiration pneumonia and sepsis, both functions of poor tone, protective reflexes, and mobility.
[84]
Congenital Zika Syndrome—Assessing the Need for a Family ...
May 19, 2020 · 78.3% reported drastic life changes, 71.0% reported anxiety, 73.4% reported excellent family support. Personal sacrifice burden score highest.
[85]
[PDF] Early stimulation for neuropsychomotor development in children with ...
Objective: To systematically review studies on the effects of early stimulation on the neuropsychomotor development of children with microcephaly.Missing: 2020-2025 | Show results with:2020-2025
[86]
gaps in long-term care for children with congenital Zika syndrome ...
Jun 9, 2025 · Sustained, individualized care not only improves child health but also alleviates caregiver burden, enhances quality of life, and may prevent ...
[87]
Postnatal-Onset Microcephaly: Pathogenesis, Patterns of Growth ...
Apr 1, 2011 · Microcephaly is a common disorder of childhood with a generally unfavorable prognosis. Most microcephaly is congenital, although some cases ...<|separator|>
[88]
The Microcephaly Epidemic Research Group Paediatric Cohort ...
Apr 1, 2021 · This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG–PC).
[89]
Study Details | NCT04816175 | Intensive Therapy for Children With ...
This trial will consist of a clinical series of up to 50 children with Global Developmental Delay and concomitant microcephaly or hyperkinetic movements.
[90]
Pediatric neurodevelopment by prenatal Zika virus exposure: a ...
Oct 10, 2020 · The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related ...
[91]
Population-Based Microcephaly Surveillance in the United States ...
Congenital microcephaly has been associated with other exposures or conditions including placental insufficiency in utero, poorly controlled maternal diabetes, ...
[92]
Microcephaly Prevalence in Infants Born to Zika Virus-Infected Women
Aug 5, 2017 · In Europe, estimates point to 1.53 per 10,000 live births (0.02%) [26] and in the USA, 8.7 per 10,000 live births (0.09%) [27]. Therefore, Zika ...Missing: global | Show results with:global
[93]
Prevalence and diagnostic accuracy of microcephaly in a pediatric ...
Oct 18, 2020 · During this period, the prevalence of microcephaly was 4.4 per 10,000 live births (5.4 cases per 10,000 live births in Brazil). Other studies ...
[94]
The genetic epidemiology of the form of microcephaly ascribed to ...
They state that the incidence of MCPH is ~1 in 10,000 in consanguineous populations and less in non-consanguineous populations. They claim that MCPH2 ...
[95]
Prevalence and clinical profile of microcephaly in South America pre ...
Nov 21, 2017 · The association between consanguinity and neural only microcephaly was strong (odds ratio 3.1, 95% confidence interval 1.4 to 7.0) (table 4⇓). ...
[96]
Brazilian studies highlight Zika microcephaly patterns - CIDRAP
Jan 16, 2018 · They estimated that 2 to 5 babies per 1,000 live births in Paraiba state had Zika-related microcephaly. They said the high rates of microcephaly ...<|separator|>
[97]
Increase in Reported Prevalence of Microcephaly in Infants Born to ...
Mar 11, 2016 · The prevalence of microcephaly in 15 states with laboratory-confirmed Zika virus transmission (2.8 cases per 10,000 live births) significantly ...Missing: global | Show results with:global
[98]
Articles Risk factors for congenital anomaly in a multiethnic birth cohort
High levels of educational attainment were associated with reduced risk in all ethnic groups, and advanced maternal age was associated with increased risk.<|separator|>
[99]
Mapping the risk of Zika virus infections in pregnant persons and ...
Jul 9, 2025 · The results showed that areas with higher poverty had more cases of Zika in pregnant women and more babies born with microcephaly. This ...Missing: status | Show results with:status
[100]
Autosomal Recessive Primary Microcephaly (MCPH): A Review of ...
There are at least seven MCPH loci, and four of the genes have been identified: MCPH1, encoding Microcephalin; MCPH3, encoding CDK5RAP2; MCPH5, encoding ASPM; ...
[101]
Zika Virus Infection - The New England Journal of Medicine
Oct 10, 2019 · Panel A shows the number of reported cases of ZIKV infection in the Americas, Pacific Islands, Africa, and Asia, as well as the cumulative.
[102]
Underreporting of Fatal Congenital Zika Syndrome, Mexico, 2016 ...
Jul 6, 2019 · We found that an estimated 50% more infants died from microcephaly attributable to congenital Zika syndrome during 2016–2017 than were reported ...
[103]
PAHO/WHO calls on countries to strengthen surveillance of birth ...
While the guidelines focus on microcephaly, they will also help countries strengthen their broader responses in relation to congenital defects.Missing: underreporting developing
[104]
the Latin American Network of Congenital Malformations 2010–2017
Nov 23, 2021 · This study used data from ReLAMC registries to quantify the prevalence of microcephaly from 2010 to 2017 (before, during and after the Zika virus epidemic).
[105]
Global burden and incidence trends of zika virus infection among ...
The ZIKV infection incidence rates in the five SDI regions peaked in 2016 and exhibited a marked increase followed by a decline between 2011 and 2021. The high ...
[106]
Zika epidemiology update - May 2024
The map of countries with Zika transmission and list of countries with Zika and vectors has been updated to reflect data as of May 2024.Missing: microcephaly CMV screening
[107]
Identification of microcephalin, a protein implicated in determining ...
Primary microcephaly (MIM 251200) is an autosomal recessive neurodevelopmental condition in which there is a global reduction in cerebral cortex volume.Missing: discovery et al paper
[108]
The Epidemic of Zika Virus–Related Microcephaly in Brazil
By the end of 2015, 4180 cases of suspected microcephaly had been reported. Zika spread to other American countries and, in February 2016, the World Health ...
[109]
the exhibition of neurologic disorders at "The Greatest Show on Earth"
Nov 30, 2010 · More than 20 performers were exhibited as "pinheads," popularly portrayed as "missing links" or children from lost civilizations.Missing: Zip case credible
[110]
Molecular Genetics of Microcephaly Primary Hereditary: An Overview
Apr 30, 2021 · Mutations in MCPH1 are the third most frequent cause of MCPH accounting for approximately 8% of the cases [9]. Microcephalin 1 has various ...
[111]
Current Status of Zika Virus Vaccines: Successes and Challenges
The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré ...