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Clinics in Perinatology Sep 2022Macrocephaly is a common diagnosis in the pediatric population, particularly in the infantile time period. There is a wide range of causes of macrocephaly, from benign... (Review)
Review
Macrocephaly is a common diagnosis in the pediatric population, particularly in the infantile time period. There is a wide range of causes of macrocephaly, from benign to malignant, for which imaging plays a key role in the diagnosis and clinical guidance. Our aim is to review the distinct and prevalent neuroimaging findings in the evaluation of the macrocephalic infant.
Topics: Child; Humans; Infant; Megalencephaly; Neuroimaging
PubMed: 36113931
DOI: 10.1016/j.clp.2022.05.006 -
Pediatric Radiology May 2021Enlarged subarachnoid spaces are a common finding in infants and young children imaged for macrocephaly or an enlarging head circumference, and benign enlargement of the... (Review)
Review
Enlarged subarachnoid spaces are a common finding in infants and young children imaged for macrocephaly or an enlarging head circumference, and benign enlargement of the subarachnoid spaces is often diagnosed. Infrequently, presumed "spontaneous" subdural hemorrhages or subdural collections might complicate these enlarged subarachnoid spaces. Children with large bilateral subdural collections might also present for imaging with macrocephaly. Each scenario potentially raises concerns for prior injury because subdural hemorrhage is a frequent finding in children with abusive head trauma.
Topics: Child; Child Abuse; Child, Preschool; Craniocerebral Trauma; Hematoma, Subdural; Humans; Infant; Megalencephaly; Subarachnoid Space
PubMed: 33999235
DOI: 10.1007/s00247-020-04848-1 -
Pediatric Clinics of North America Aug 2021Macrocephaly is commonly encountered in the primary care provider's office. It is defined as an occipitofrontal circumference that is greater than 2 standard deviations... (Review)
Review
Macrocephaly is commonly encountered in the primary care provider's office. It is defined as an occipitofrontal circumference that is greater than 2 standard deviations above the mean for the child's given age. Macrocephaly is a nonspecific clinical finding that may be benign or require further evaluation. An algorithmic approach is useful for aiding in the clinical decision-making process to determine if further evaluation with neuroimaging is warranted. Abnormal findings may signify a harmful underlying cause, requiring referral to a genetic specialist or neurosurgeon.
Topics: Child; Child Development; Child Welfare; Humans; Megalencephaly; Nervous System Diseases; Primary Health Care
PubMed: 34247707
DOI: 10.1016/j.pcl.2021.04.004 -
Topics in Magnetic Resonance Imaging :... Aug 2018Macrocephaly is a relatively common clinical condition affecting up to 5% of the pediatric population. It is defined as an abnormally large head with an occipitofrontal... (Review)
Review
Macrocephaly is a relatively common clinical condition affecting up to 5% of the pediatric population. It is defined as an abnormally large head with an occipitofrontal circumference greater than 2 standard deviations above the mean for a given age and sex. Megalencephaly refers exclusively to brain overgrowth exceeding twice the standard deviation. Macrocephaly can be isolated and benign or may be the first indication of an underlying congenital, genetic, or acquired disorder, whereas megalencephaly is more often syndromic. Megalencephaly can be divided into 2 subtypes: metabolic and developmental, caused by genetic defects in cellular metabolism and alterations in signaling pathways, respectively. Neuroimaging plays an important role in the evaluation of macrocephaly, especially in the metabolic subtype which may not be overtly apparent clinically. This article outlines the diverse etiologies of macrocephaly, delineates their clinical and radiographic features, and suggests a clinicoradiological algorithm for evaluation.
Topics: Brain; Female; Humans; Magnetic Resonance Imaging; Male; Megalencephaly
PubMed: 30086108
DOI: 10.1097/RMR.0000000000000170 -
Prenatal Diagnosis Dec 2023Macrocephaly means a large head and is defined as a head circumference (HC) above the 98th percentile or greater than +2SD above the mean for gestational age.... (Review)
Review
Macrocephaly means a large head and is defined as a head circumference (HC) above the 98th percentile or greater than +2SD above the mean for gestational age. Macrocephaly can be primary and due to increased brain tissue (megalocephaly), which in most cases is familial and benign or secondary. The latter may be due to various causes, including but not limited to communicating or non-communicating hydrocephalus, cerebral edema, focal and pericerebral increased fluid collections, thickened calvarium and brain tumors. Megalocephaly can be syndromic or non-syndromic. In the former, gyral and structural CNS anomalies are common. It is important to exercise caution when considering a diagnosis of megalocephaly due to limitations in the accuracy of HC measurement, lack of nomograms for specific populations, inconsistencies between prenatal and postnatal HC growth curves and progression over time. The degree of macrocephaly is important, with mild macrocephaly ≤2.5SD carrying a good prognosis, especially when one of the parents has macrocephaly and normal development. Cases in which the patient history and/or physical exam are positive or when parental HC are normal are more worrisome and warrant a neurosonogram, fetal MRI and genetic testing to better delineate the underlying etiology and provide appropriate counseling.
Topics: Pregnancy; Female; Humans; Prenatal Diagnosis; Megalencephaly; Genetic Testing; Gestational Age; Magnetic Resonance Imaging
PubMed: 38009873
DOI: 10.1002/pd.6473 -
Pediatric Emergency Medicine Practice Aug 2023Although the cause of macrocephaly is found to be benign in many cases, the large differential diagnosis includes conditions that can be life-threatening. Prompt... (Review)
Review
Although the cause of macrocephaly is found to be benign in many cases, the large differential diagnosis includes conditions that can be life-threatening. Prompt recognition and timely diagnosis can lead to a better prognosis in many cases. This issue summarizes the available literature on macrocephaly and provides recommendations for the evaluation, diagnosis, and appropriate disposition of children with macrocephaly in the acute setting. Developmental milestones, "red flags," and neurologic examination by age are reviewed to help narrow the differential diagnosis and identify underlying etiologies. Guidance is provided for which imaging studies are indicated, and recommendations are given for which children need transfer or admission.
Topics: Child; Humans; Diagnosis, Differential; Diagnostic Imaging; Emergency Service, Hospital; Megalencephaly; Neurologic Examination
PubMed: 37486089
DOI: No ID Found -
American Journal of Human Genetics Nov 2018Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by...
Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α-subunit of the voltage-gated Ca2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
Topics: Adolescent; Adult; Calcium Channels, R-Type; Cation Transport Proteins; Child; Child, Preschool; Contracture; Dyskinesias; Epilepsy; Female; Genetic Variation; Humans; Infant; Male; Megalencephaly; Neurodevelopmental Disorders; Spasms, Infantile
PubMed: 30343943
DOI: 10.1016/j.ajhg.2018.09.006 -
American Journal of Medical Genetics.... Dec 2019The nucleosome remodeling and deacetylase (NuRD) complex is a major regulator of gene expression involved in pluripotency, lineage commitment, and corticogenesis. This... (Review)
Review
The nucleosome remodeling and deacetylase (NuRD) complex is a major regulator of gene expression involved in pluripotency, lineage commitment, and corticogenesis. This important complex is composed of seven different proteins, with mutations in CHD3, CHD4, and GATAD2B being associated with neurodevelopmental disorders presenting with macrocephaly and intellectual disability similar to other overgrowth and intellectual disability (OGID) syndromes. Pathogenic variants in CHD3 and CHD4 primarily involve disruption of enzymatic function. GATAD2B variants include loss-of-function mutations that alter protein dosage and missense variants that involve either of two conserved domains (CR1 and CR2) known to interact with other NuRD proteins. In addition to macrocephaly and intellectual disability, CHD3 variants are associated with inguinal hernias and apraxia of speech; whereas CHD4 variants are associated with skeletal anomalies, deafness, and cardiac defects. GATAD2B-associated neurodevelopmental disorder (GAND) has phenotypic overlap with both of these disorders. Of note, structural models of NuRD indicate that CHD3 and CHD4 require direct contact with the GATAD2B-CR2 domain to interact with the rest of the complex. Therefore, the phenotypic overlaps of CHD3- and CHD4-related disorders with GAND are consistent with a loss in the ability of GATAD2B to recruit CHD3 or CHD4 to the complex. The shared features of these neurodevelopmental disorders may represent a new class of OGID syndrome: the NuRDopathies.
Topics: DNA-Binding Proteins; Humans; Megalencephaly; Mi-2 Nucleosome Remodeling and Deacetylase Complex; Neurodevelopmental Disorders; Syndrome
PubMed: 31737996
DOI: 10.1002/ajmg.c.31752 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2022Reduction cranioplasty for extreme hydrocephalic macrocephaly is performed for acquiring motor skills (head holding, sitting, moving), aesthetic correction and social... (Review)
Review
Reduction cranioplasty for extreme hydrocephalic macrocephaly is performed for acquiring motor skills (head holding, sitting, moving), aesthetic correction and social adaptation of children. The authors analyze literature data and describe 2 patients with congenital hydrocephalic macrocephaly who underwent shunting surgery followed by reduction cranioplasty in early age using resorbable mini-plates. Reduction cranioplasty decreased skull volume, improved social adaptation of children and ensured favorable aesthetic outcome.
Topics: Child; Humans; Hydrocephalus; Megalencephaly; Plastic Surgery Procedures; Skull
PubMed: 35170281
DOI: 10.17116/neiro20228601191 -
Pediatric Radiology May 2021Macrocephaly is a common finding in infants and is often idiopathic or familial. In the absence of clinical signs and symptoms, it can be difficult to determine when...
BACKGROUND
Macrocephaly is a common finding in infants and is often idiopathic or familial. In the absence of clinical signs and symptoms, it can be difficult to determine when concern for underlying pathology is justified.
OBJECTIVES
The objectives of this study were to determine the utility of screening head ultrasound (US) in asymptomatic infants with macrocephaly and to identify clinical factors associated with significant US findings.
MATERIALS AND METHODS
A 20-year retrospective review was performed of infants undergoing head US for macrocephaly or rapidly increasing head circumference. Data collected included age, gender, head circumference at birth and at the time of US, specialty of the ordering physician, US findings, computed tomography (CT) or magnetic resonance imaging (MRI) findings, and clinical course including interventions.
RESULTS
Four hundred and forty infants met inclusion criteria. Two hundred and eighty studies (64%) were found to be normal, 137 (31%) had incidental findings, 17 (3.8%) had indeterminate but potentially significant findings, and 6 (1.4%) had significant findings. Twenty of the 23 infants with indeterminate or significant findings had subsequent CT or MRI. This confirmed significant findings in eight infants (1.8%): three subdural hematomas, two intracranial tumors, two aqueductal stenoses, and one middle fossa cyst. Five of the eight infants required surgical procedures. The only statistically significant association found with having a significant finding on head US was head circumference at birth.
CONCLUSION
Ultrasound is a useful initial study to evaluate infantile macrocephaly, identifying several treatable causes in our study and, when negative, effectively excluding significant pathology.
Topics: Humans; Hydrocephalus; Infant; Infant, Newborn; Magnetic Resonance Imaging; Megalencephaly; Retrospective Studies; Ultrasonography
PubMed: 33399982
DOI: 10.1007/s00247-020-04907-7