Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further

medical test A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic ...

s to determine whether the

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...

is accompanied by particular disorders. Those with benign or familial macrocephaly are considered to have megalencephaly.

Causes

Many people with abnormally large heads or large skulls are healthy, but macrocephaly may be pathological. Pathologic macrocephaly may be due to megalencephaly (enlarged brain),

hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary i ...

(abnormally increased

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

), cranial hyperostosis (bone overgrowth), and other conditions. Pathologic macrocephaly is called "syndromic", when it is associated with any other noteworthy condition, and "nonsyndromic" otherwise. Pathologic macrocephaly may be caused by

congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

anatomic abnormalities, genetic conditions, or by environmental events. Many genetic conditions are associated with macrocephaly, including familial macrocephaly related to the holgate gene,

autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

, ''PTEN'' mutations such as Cowden disease,

neurofibromatosis Neurofibromatosis (NF) is a group of three conditions in which tumors grow in the nervous system. The three types are neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis. In NF1 symptoms include light brown ...

type 1, and

tuberous sclerosis Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination ...

; overgrowth syndromes such as Sotos syndrome (cerebral gigantism), Weaver syndrome,

Simpson–Golabi–Behmel syndrome Simpson–Golabi–Behmel syndrome (SGBS), is a rare inherited congenital disorder that can cause craniofacial, skeletal, cardiac, and renal abnormalities. The syndrome is inherited in an X-linked recessive fashion, where males express the phenoty ...

(bulldog syndrome), and macrocephaly-capillary malformation ( M-CMTC) syndrome; neurocardiofacial-cutaneous syndromes such as Noonan syndrome, Costello syndrome,

Gorlin syndrome Gorlin may refer to: People * Dan Gorlin, computer game programmer, designer and founder of Dan Gorlin Productions * Eitan Gorlin, filmmaker, author and actor * Mikhail Gorlin, Russian emigre poet * Richard Gorlin, American cardiologist, co-devel ...

, (also known as Basal Cell Nevus Syndrome) and cardiofaciocutaneous syndrome;

Fragile X syndrome Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features ma ...

; leukodystrophies (brain

white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribu ...

degeneration) such as

Alexander disease Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins durin ...

Canavan disease Canavan disease, or Canavan-Van Bogaert-Bertrand disease, is a rare and fatal autosomal recessive degenerative disease that causes progressive damage to nerve cells and loss of white matter in the brain. It is one of the most common degenerative ...

, and megalencephalic leukoencephalopathy with subcortical cysts; and glutaric aciduria type 1 and

D-2-hydroxyglutaric aciduria 2-hydroxyglutaric aciduria is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in one's urine. It is either autosomal recessive or autosomal dominant. Presentation The signs/symptoms of this ...

. At one end of the genetic spectrum, duplications of chromosomes have been found to be related to

and macrocephaly; at the other end, deletions of chromosomes have been found to be related to

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

and

microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

. Environmental events associated with macrocephaly include infection, neonatal intraventricular hemorrhage (bleeding within the infant brain), subdural hematoma (bleeding beneath the outer lining of the brain), subdural effusion (collection of fluid beneath the outer lining of the brain), and

arachnoid cyst Arachnoid cysts are cerebrospinal fluid covered by arachnoidal cells and collagen that may develop between the surface of the brain and the cranial base or on the arachnoid membrane, one of the three meningeal layers that cover the brain and the ...

s (cysts on the brain surface). In research, cranial height or brain imaging may be used to determine intracranial volume more accurately. Below is a list of causes of macrocephaly from ''Swaiman's Pediatric Neurology: Principles and Practice'' noted in ''The Little Black Book of Neurology:''

Hydrocephalus

Noncommunicating

Arnold–Chiari malformation Chiari malformation (CM) is a structural defect in the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum (the opening at the base of the skull). CMs can cause headaches, difficulty ...

* Aqueductal stenosis * X-linked

with stenosis of the aqueduct of Sylvius (HSAS) syndrome (

L1CAM L1, also known as L1CAM, is a transmembrane protein member of the L1 protein family, encoded by the L1CAM gene. This protein, of 200-220 kDa, is a neuronal cell adhesion molecule with a strong implication in cell migration, adhesion, neurite outg ...

) * Dandy–Walker malformation * Galenic

vein Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated ...

aneurysm An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus ( ...

malformation A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities ca ...

Neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s, supratentorial, and infratentorial *

Arachnoid cyst Arachnoid cysts are cerebrospinal fluid covered by arachnoidal cells and collagen that may develop between the surface of the brain and the cranial base or on the arachnoid membrane, one of the three meningeal layers that cover the brain and the ...

, infratentorial *

Holoprosencephaly Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres, typically occurring between the 18th and 28th day of gestation. Normally, the forebrain is formed ...

with dorsal interhemispheric sac

Communicating

* External or extraventricular obstructive hydrocephalus ( dilated subarachnoid space)

Arachnoid cyst, supratentorial

Meningeal fibrosis/obstruction

* Postinflammatory * Posthemorrhagic * Neoplastic infiltration Pankreaslipom 67jm - CT axial und coronar - 001

Vascular

Arteriovenous malformation Arteriovenous malformation is an abnormal connection between arteries and veins, bypassing the capillary system. This vascular anomaly is widely known because of its occurrence in the central nervous system (usually cerebral AVM), but can app ...

Intracranial hemorrhage Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds (intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural blee ...

Dural sinus thrombosis Dural is a suburb of Sydney, in the state of New South Wales, Australia 36 kilometres north-west of the Sydney central business district in the local government areas of Hornsby Shire and The Hills Shire. Dural is part of the Hills District ...

Choroid plexus papilloma

Neurocutaneous syndromes

* Incontinentia pigmenti

Destructive lesions

* Hydranencephaly * Porencephaly

Familial, autosomal-dominant, autosomal-recessive, X-linked

Subdural fluid

Hematoma A hematoma, also spelled haematoma, or blood suffusion is a localized bleeding outside of blood vessels, due to either disease or trauma including injury or surgery and may involve blood continuing to seep from broken capillaries. A hematoma is ...

* Hygroma * Empyema

Brain edema (toxic-metabolic)

* Intoxication *

Lead Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cut, ...

Vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...

Tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects in ...

Endocrine The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neur ...

( hypoparathyroidism, hypoadrenocorticism) * Galactosemia *

Idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...

( pseudotumorcerebri)

Thick skull or scalp (hyperostosis)

* Familial variation *

Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

Osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone a ...

, severe precocious autosomal-recessive osteoporosis ( CLCN7,

TCIRG1 The TCIRG1 (T cell immune regulator 1) gene encodes for the V-type proton ATPase (V-ATPase) 116 kDa subunit a isoform 3 enzyme. Gene TCIRG1 (T cell immune regulator 1) is a gene that encodes the V-type proton ATPase (V-ATPase) 116 kDa subu ...

) * Pycnodysostosis ( CTSK) *

Craniometaphyseal dysplasia Craniometaphyseal dysplasia is a rare skeletal disorder that results from a mutation in the ANKH or GJA1 genes. The condition is characterized abnormal facial features, impairment of cranial nerves, and malformation of the long bones in the limbs ...

( ANKH) *

Craniodiaphyseal dysplasia Craniodiaphyseal dysplasia (CDD), also known as lionitis, is an extremely rare autosomal recessive bone disorder that causes calcium to build up in the skull, disfiguring the facial features and reducing life expectancy. These calcium deposits dec ...

* Pyle dysplasia * Sclerosteosis (

SOST Sost or SOST may refer to: Places * Sost, Afghanistan, a village in Badakhshan Province *Sost, Pakistan Sost or Sust ( ur, ) is a village in Gojal, Upper Hunza, Gilgit–Baltistan, Pakistan. It is the last town inside Pakistan on the Karak ...

) * Juvenile Paget disease *

hyperphosphatasia * Familial osteoectasia *

Osteogenesis imperfecta Osteogenesis imperfecta (; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that break easily. The range of symptoms—on the skeleton as well as on the body's other organs—may be ...

Rickets Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications ma ...

Cleidocranial dysostosis Cleidocranial dysostosis (CCD), also called cleidocranial dysplasia, is a birth defect that mostly affects the bones and teeth. The collarbones are typically either poorly developed or absent, which allows the shoulders to be brought close togeth ...

* Hyperostosis corticalis generalisata ( van Buchem disease) * Proteus syndrome

Megalencephaly and hemimegalencephaly

* Megalencephaly * Hemimegalencephaly

Diagnosis

Macrocephaly is customarily diagnosed if head circumference is greater than two

standard deviation In statistics, the standard deviation is a measure of the amount of variation or dispersion of a set of values. A low standard deviation indicates that the values tend to be close to the mean (also called the expected value) of the set, whil ...

s (SDs) above the mean. Relative macrocephaly occurs if the measure is less than two SDs above the mean, but is disproportionately above that when ethnicity and stature are considered. Diagnosis can be determined in utero or can be determined within 18–24 months after birth in some cases where head circumference tends to stabilize in

infant An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used t ...

s. Diagnosis in infants includes measuring the circumference of the child's head and comparing how significant it falls above the 97.5 percentile of children similar to their demographic. If falling above the 97.5th percentile then the patient will be checked to determine whether there is any

intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury ( mmHg) and at rest, is normally 7–15 mmHg for a supine adul ...

present and whether or not immediate surgery is needed. If immediate surgery is not needed then further testing will be done to determine whether the patient has either macrocephaly or benign macrocephaly. Diagnosis for macrocephaly involves the comparison of the infant's head circumference to that of other infants of the same age and

ethnicity An ethnic group or an ethnicity is a grouping of people who identify with each other on the basis of shared attributes that distinguish them from other groups. Those attributes can include common sets of traditions, ancestry, language, history, ...

. If a patient is suspected of having macrocephaly molecular testing will be used to confirm diagnosis. Symptoms vary on the cause of macrocephaly on the child and if the child has any other accompanying syndromes which will be determined through molecular testing.

Benign or familial macrocephaly

Benign macrocephaly can occur without reason or be inherited by one or both parents (in which it is considered benign familial macrocephaly and is considered megalencephaly form of macrocephaly). Diagnoses for familial macrocephaly is determined by measuring the head circumference of both parents and comparing it to the child's. Benign and familial macrocephaly is not associated with

neurological disorder A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakn ...

s. While benign and familial macrocephaly does not result in neurological disorders, neurodevelopment will still be assessed. Although neurological disorders do not occur, temporary symptoms of benign and familial macrocephaly include:

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech ...

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

, and mild hypotonia. Neurodevelopment is assessed for all cases and suspected cases of macrocephaly to determine whether and what treatments may be needed, and whether any other syndrome/s may be present or likely to develop.

Treatment

Treatment varies depending on whether or not it occurs with other medical conditions in the child and where

is present. If benign and found between the brain and skull then no surgery is needed. If excess fluid is found between the ventricle spaces in the brain then surgery will be needed.

Associated syndromes

Below is a list of

s associated with macrocephaly that are noted in ''Signs and Symptoms of Genetic Conditions: A Handbook''. Lujan

Include multiple major and or minor anomalies

Acrocallosal syndrome Acrocallosal syndrome (also known as ACLS) is an extremely rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and intellectual disabilities, and other symptoms. The syndrom ...

* Apert syndrome *

Bannayan–Riley–Ruvalcaba syndrome Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare overgrowth syndrome and hamartomatous disorder with occurrence of multiple subcutaneous lipomas, macrocephaly and hemangiomas. The disease is inherited in an autosomal dominant manner. The dis ...

* Cardiofaciocutaneous syndrome * Chromosome 14 - maternal disomy * Chromosome 22qter deletion *

* Costello syndrome * Encephalocraniocutaneous lipomatosis * FG syndrome * Hallermann–Streiff syndrome * Hydrolethalus syndrome * Hypomelanosis syndrome * Hypomelanosis of Ito * Kelvin Peter anomaly plus syndrome * Lujan–Fryns syndrome * Macrocephaly-CM (MCAP) * Marshall–Smith syndrome * Neuhauser megalocornea/MR syndrome * Neurofibromatosis type I *

Nevoid basal-cell carcinoma syndrome Nevoid basal-cell carcinoma syndrome (NBCCS) is an inherited medical condition involving defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones. People with this syndrome are particularly prone to ...

* Noonan syndrome * Ocular-ectodermal syndrome * Osteopathia striata - cranial sclerosis *

Perlman syndrome Perlman syndrome (PS) (also called renal hamartomas, nephroblastomatosis and fetal gigantism) is a rare overgrowth disorder present at birth. It is characterized by polyhydramnios and fetal overgrowth, including macrocephaly, neonatal macrosomia, ...

* Robinow syndrome *

* Sotos syndrome * Sturge–Weber syndrome * Weaver syndrome * Wiedemann–Rautenstrauch syndrome * 3C syndrome Boomerang splenial infarct

Secondary to a metabolic disorder

* Glutaric aciduria type II *

GM1 gangliosidosis The GM1 gangliosidoses, usually shortened to GM1, are gangliosidoses caused by mutation in the GLB1 gene resulting in a deficiency of beta-galactosidase. The deficiency causes abnormal storage of acidic lipid materials in cells of the central and ...

* Hunter syndrome * Hurler syndrome *

MPS VII Sly syndrome, also called mucopolysaccharidosis type VII (MPS-VII), is an autosomal recessive lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase. This enzyme is responsible for breaking down large sugar molecules calle ...

Sanfilippo syndrome Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and spinal cord. It is caused by a buildup of large sugar molecules called gly ...

* Zellweger syndrome Alexander autopsy

Associated with a skeletal dysplasia

Achondroplasia Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected ha ...

Campomelic dysplasia Campomelic dysplasia (CMD) is a genetic disorder characterized by bowing of the long bones and many other skeletal and extraskeletal features. It can be lethal in the neonatal period due to respiratory insufficiency, but the severity of the diseas ...

* Hypochondrogenesis * Hypochondroplasia * Kenny-Caffey syndrome * Kniest dysplasia * Lenz–Majewski syndrome * Osteogenesis imperfecta III * Osteopetrosis, autosomal recessive form * Schneckenbecken dysplasia * Sclerosteosis * Short rib syndrome, beemer-langer type *

Short rib-polydactyly 2 (majewski type) Short may refer to: Places * Short (crater), a lunar impact crater on the near side of the Moon * Short, Mississippi, an unincorporated community * Short, Oklahoma, a census-designated place People * Short (surname) * List of people known as ...

* Spondyloepiphyseal dysplasia congenita *

Thanatophoric dysplasia Thanatophoric dysplasia is a severe skeletal disorder characterized by a disproportionately small ribcage, extremely short limbs and folds of extra skin on the arms and legs. Symptoms and signs Infants with this condition have disproportionately ...

With no obvious physical findings

* Cobalamin deficiency (combined methylmalonic aciduria and

homocystinuria Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to i ...

) * Dandy–Walker malformation * Glutaric aciduria type 1 *

L-2-hydroxyglutaric aciduria 2-hydroxyglutaric aciduria is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in one's urine. It is either autosomal recessive or autosomal dominant. Presentation The signs/symptoms of thi ...

* Megalencephalic leukoencephalopathy with subcortical cysts *

Osteogenesis imperfecta IV Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts funct ...

* Osteopathia striata-cranial sclerosis * Periventricular heterotopia *

Sandhoff disease Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, ...

Tay–Sachs disease Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around three to six months of age, with the baby ...

References

External links

GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)

GeneReviews/NCBI/NIH/UW entry on 9q22.3 Microdeletion
{{Authority control Congenital disorders of musculoskeletal system