Microcephaly

Abstract

Microcephaly is defined as a head circumference more than two standard deviations below the mean for gender and age. Congenital microcephaly is present at birth, whereas postnatal microcephaly occurs later in life. Genetic abnormalities, syndromes, metabolic disorders, teratogens, infections, prenatal, perinatal, and postnatal injuries can cause both congenital and postnatal microcephaly. Evaluation of patients with microcephaly begins with a thorough history and physical examination. In cases of worsening microcephaly or neurological signs or symptoms, neuroimaging, metabolic, or genetic testing should be strongly considered. Any further studies and workup should be directed by the presence of signs or symptoms pointing to an underlying diagnosis and are usually used as confirmatory testing for certain conditions. Neuroimaging with magnetic resonance imaging (MRI) is often the first diagnostic test in evaluating children with microcephaly. Genetic testing is becoming more common and is often the next step following neuroimaging when there is no specific evidence in the history or physical examination suggesting a diagnosis. Microcephaly is a lifelong condition with no known cure. The prognosis is usually worse for children who experienced an intrauterine infection or have a chromosomal or metabolic abnormality. Zika virus has rapidly spread since 2015, and maternal infection with this virus is associated with microcephaly and other serious brain abnormalities. Microcephaly has become much more prevalent in the news and scientific community with the recent emergence of Zika virus as a cause of congenital microcephaly.

Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly

“…Primary microcephaly is a neurodevelopmental disorder in which brain volume is markedly reduced, directly reflecting a smaller cerebral cortex 23 , with occipito-frontal head circumference (OFC) >2-3 standard deviations (SD) below the mean [24][25][26] . The causes of microcephaly are numerous, including prenatal exposure to toxins such as alcohol, in utero infections such as Zika virus, and metabolic/genetic factors 23,24,27,28 .…”

“…Primary microcephaly is a neurodevelopmental disorder in which brain volume is markedly reduced, directly reflecting a smaller cerebral cortex 23 , with occipito-frontal head circumference (OFC) >2-3 standard deviations (SD) below the mean [24][25][26] . The causes of microcephaly are numerous, including prenatal exposure to toxins such as alcohol, in utero infections such as Zika virus, and metabolic/genetic factors 23,24,27,28 . Mutations in genes involved in centriolar biogenesis/assembly (MCPH), microtubule regulation (TUB genes), DNA damage (PNKP), signaling pathways (ALFY/ASPM), transcription and metabolism are linked to microcephaly [29][30][31][32][33][34][35] .…”

Molecular Genetics of Microcephaly Primary Hereditary: An Overview

“…Microcephaly, from the Greek word μικροκεφαλία (mikrokephalia), meaning small head, is a term used to describe a cranium with reduction of the occipitofrontal head circumference equal, or more that teo standard deviations below the mean for age, gender, and ethnicity [ 1 , 2 , 3 , 4 , 5 , 6 ]. Microcephaly usually reflects a small brain volume; it is presented either as an isolated finding (non-syndromic) or with additional features, such as dysostoses and short stature (for example Seckel syndrome, Meier-Gorlin syndrome), radiosensitivity, and chromosome breakage (for example, Bloom syndrome), or diabetes (for example, Wolcott Rallison syndrome) [ 1 , 3 , 4 ]. The underlying etiology of microcephaly varies; it can be environmental, resulting, for instance, from exposure to toxic substances, or genetic [ 2 , 4 ].…”

“…MCPH is a rare disease (1:10,000 to 1:250,000 live births) most frequently diagnosed in populations with consanguineous marriages [ 5 , 7 , 8 , 9 , 10 ]. The brain of MCPH patients is small, its architecture is largely normal, yet with simplified neocortical gyration [ 1 , 3 , 4 , 5 , 6 , 7 ]. Additionally, in some cases radiological studies reveal further abnormalities, for instance corpus callosum agenesis or hypoplasia, enlarged lateral ventricles, and cerebellar or brain stem hypoplasia [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Head CT: Toward Making Full Use of the Information the X-Rays Give

“…This is the reasoning by which the diagnosis is made for microcephaly (head circumference . 2 SD below the mean for sex and age) 34 or macrocephaly (head circumference of . 2 SD above the mean for age and sex).…”