Macrocephaly

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 tests to determine whether the syndrome 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 (abnormally increased cerebrospinal fluid), 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 anatomic abnormalities, genetic conditions, or by environmental events.
Many genetic conditions are associated with macrocephaly, including familial macrocephaly related to the holgate gene, autism, PTEN mutations such as Cowden disease, neurofibromatosis type 1, and tuberous sclerosis; overgrowth syndromes such as Sotos syndrome (cerebral gigantism), Weaver syndrome, Simpson–Golabi–Behmel syndrome (bulldog syndrome), and macrocephaly-capillary malformation (M-CMTC) syndrome; neurocardiofacial-cutaneous syndromes such as Noonan syndrome, Costello syndrome, Gorlin syndrome, (also known as Basal Cell Nevus Syndrome) and cardiofaciocutaneous syndrome; Fragile X syndrome; leukodystrophies (brain white matter degeneration) such as Alexander disease, Canavan disease, and megalencephalic leukoencephalopathy with subcortical cysts; and glutaric aciduria type 1 and D-2-hydroxyglutaric aciduria.
At one end of the genetic spectrum, duplications of chromosomes have been found to be related to autism and macrocephaly; at the other end, deletions of chromosomes have been found to be related to schizophrenia and microcephaly.
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 cysts (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 conditions featuring macrocephaly from NCBI's MedGen:
Achondroplasia
Acrocallosal syndrome
Adams-Oliver syndrome
Adenosine kinase deficiency
Antley-Bixler syndrome
Autosomal dominant Kenny-Caffey syndrome
Autosomal recessive osteopetrosis
Axenfeld-Rieger anomaly
B4GALT1-congenital disorder of glycosylation
Bardet-Biedl syndrome
Brittle cornea syndrome
Camptomelic dysplasia
Cardio-facio-cutaneous syndrome
Cobblestone lissencephaly without muscular or ocular involvement
Coffin-Siris syndrome
Cohen-Gibson syndrome
Cole-Carpenter syndrome
Congenital disorder of glycosylation, type Iw, autosomal dominant
Corpus callosum, agenesis of
Costello syndrome
Cowden syndrome
Craniodiaphyseal dysplasia, autosomal dominant
Cranioectodermal dysplasia
Craniometaphyseal dysplasia
Craniosynostosis
D-2-hydroxyglutaric aciduria
Deficiency of alpha-mannosidase
Desmosterolosis
Donnai-Barrow syndrome
Early-onset parkinsonism-intellectual disability syndrome
Ehlers-Danlos syndrome, spondylodysplastic type
Epidermolysis bullosa simplex
Fragile X syndrome
Giant axonal neuropathy
Glutaric aciduria, type 1
Gorlin syndrome
Greenberg dysplasia
Greig cephalopolysyndactyly syndrome
Hamartoma of hypothalamus
Holoprosencephaly
Hurler syndrome
Hydrocephalus, nonsyndromic, autosomal recessive
Hypochondroplasia
Hypophosphatemic rickets and hyperparathyroidism
Hypothyroidism, congenital, nongoitrous
Ito hypomelanosis
Joubert syndrome
Keipert syndrome
Legius syndrome
LEOPARD syndrome
Lethal congenital contracture syndrome
MASA syndrome
Megalencephaly, autosomal dominant
Megalocornea-intellectual disability syndrome
MGAT2-congenital disorder of glycosylation
MOMO syndrome
Mucopolysaccharidosis type 6
Mucopolysaccharidosis type 7
Mucopolysaccharidosis, MPS-II
Mucopolysaccharidosis, MPS-III-D
Muenke syndrome
Multiple acyl-CoA dehydrogenase deficiency
Multiple congenital anomalies-hypotonia-seizures syndrome
Multiple epiphyseal dysplasia, Al-Gazali type
Myhre syndrome
Neurofibromatosis, type 1
Neurofibromatosis-Noonan syndrome
Niemann-Pick disease, type A
Noonan syndrome
Opsismodysplasia
Optic atrophy
Osteopathia striata with cranial sclerosis
Pallister-Killian syndrome
Parietal foramina
Parietal foramina with cleidocranial dysplasia
Pelger-Huët anomaly
Peroxisome biogenesis disorder 1A (Zellweger)
Peroxisome biogenesis disorder 4B
Phelan-McDermid syndrome
Plasminogen deficiency, type I
Primrose syndrome
Proteus syndrome
Ritscher-Schinzel syndrome
Robinow syndrome
Sandhoff disease
Schneckenbecken dysplasia
Sclerosteosis
Severe X-linked myotubular myopathy
Sialuria
Simpson-Golabi-Behmel syndrome
Snijders Blok-Campeau syndrome
Sotos syndrome
Sturge-Weber syndrome
Sulfite oxidase deficiency due to molybdenum cofactor deficiency
Symphalangism with multiple anomalies of hands and feet
Syndromic X-linked intellectual disability
Thanatophoric dysplasia type 1
Vanishing white matter disease
Weaver syndrome
X-linked dominant chondrodysplasia, Chassaing-Lacombe type
X-linked hydrocephalus syndrome
X-linked intellectual disability with marfanoid habitus
Zimmermann-Laband syndrome
ZTTK syndrome
Diagnosis
Macrocephaly is customarily diagnosed if head circumference is greater than two standard deviations (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 infants. 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 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. 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 disorders. 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, epilepsy, 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 cerebrospinal fluid 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 syndromes associated with macrocephaly that are noted in Signs and Symptoms of Genetic Conditions: A Handbook.
Include multiple major and or minor anomalies
Acrocallosal syndrome
Apert syndrome
Bannayan–Riley–Ruvalcaba syndrome
Cardiofaciocutaneous syndrome
Chromosome 14 - maternal disomy
Chromosome 22qter deletion
Cleidocranial dysostosis
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
Noonan syndrome
Ocular-ectodermal syndrome
Osteopathia striata - cranial sclerosis
Perlman syndrome
Robinow syndrome
Simpson–Golabi–Behmel syndrome
Sotos syndrome
Sturge–Weber syndrome
Weaver syndrome
Wiedemann–Rautenstrauch syndrome
3C syndrome
Secondary to a metabolic disorder
Glutaric aciduria type II
GM1 gangliosidosis
Hunter syndrome
Hurler syndrome
MPS VII
Sanfilippo syndrome
Zellweger syndrome
Associated with a skeletal dysplasia
Achondroplasia
Campomelic dysplasia
Craniodiaphyseal dysplasia
Craniometaphyseal dysplasia
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)
Spondyloepiphyseal dysplasia congenita
Thanatophoric dysplasia
With no obvious physical findings
Alexander disease
Canavan disease
Cobalamin deficiency (combined methylmalonic aciduria and homocystinuria)
Dandy–Walker malformation
Glutaric aciduria type 1
L-2-hydroxyglutaric aciduria
Megalencephalic leukoencephalopathy with subcortical cysts
Osteogenesis imperfecta IV
Osteopathia striata-cranial sclerosis
Periventricular heterotopia
Sandhoff disease
Tay–Sachs disease
See also
Microcephaly
Megalencephaly
Hydrocephalus
References
External links
GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)
GeneReviews/NCBI/NIH/UW entry on 9q22.3 Microdeletion
Congenital disorders of musculoskeletal system