Microcephaly

"Microcephalus" redirects here. For the genus of beetle, see Microcephalus (genus).

Microcephaly
Neural scans of a skull with microcephaly (right) and a normal skull (left)
Classification and external resources
Specialty	Medical genetics
ICD-10	Q02
ICD-9-CM	742.1
OMIM	251200
DiseasesDB	22629
MedlinePlus	003272
Patient UK	Microcephaly
MeSH	D008831

Microcephaly is a neurodevelopmental disorder. It is an important neurologic sign, but no uniformity exists in its definition. It is usually defined as a head circumference (HC) more than two standard deviations below the mean for age and sex. Some academics advocate defining it as head circumference more than three standard deviations below the mean for the age and sex. Microcephaly may be congenital or it may develop in the first few years of life. The disorder may stem from a wide variety of conditions that cause abnormal growth of the brain, or from syndromes associated with chromosomal abnormalities. A homozygous mutation in one of the microcephalin genes causes primary microcephaly.

In general, life expectancy for individuals with microcephaly is reduced and the prognosis for normal brain function is poor. The prognosis varies depending on the presence of associated abnormalities.

Signs and symptoms

Affected newborns generally have striking neurological defects and seizures. Severely impaired intellectual development is common, but disturbances in motor functions may not appear until later in life.

Infants with microcephaly are born with either a normal or reduced head size. Subsequently, the head fails to grow, while the face continues to develop at a normal rate, producing a child with a small head and a receding forehead, and a loose, often wrinkled scalp. As the child grows older, the smallness of the skull becomes more obvious, although the entire body also is often underweight and dwarfed. Development of motor functions and speech may be delayed. Hyperactivity and intellectual disability are common occurrences, although the degree of each varies. Convulsions may also occur. Motor ability varies, ranging from clumsiness in some to spastic quadriplegia in others.

Causes

Microcephaly is a type of cephalic disorder. It has been classified in two types based on the onset:

Congenital

Isolated

1. Familial (autosomal recessive) microcephaly
2. Autosomal dominant microcephaly
3. X-linked microcephaly
4. Chromosomal (balanced rearrangements and ring chromosome)

Syndromes

• Chromosomal

1. Poland syndrome
2. Down syndrome
3. Edward syndrome
4. Patau syndrome
5. Unbalanced rearrangements

• Contiguous gene deletion

1. 4p deletion (Wolf–Hirschhorn syndrome)
2. 5p deletion (Cri-du-chat)
3. 7q11.23 deletion (Williams syndrome)
4. 22q11 deletion (DiGeorge syndrome)

• Single gene defects

1. Smith–Lemli–Opitz syndrome
2. Seckel syndrome
3. Cornelia de Lange syndrome
4. Holoprosencephaly
5. Primary microcephaly 4

Acquired

• Disruptive injuries

1. Ischemic stroke
2. Hemorrhagic stroke
3. Death of a monozygotic twin

• Congenital infections

1. Congenital cytomegalovirus infection
2. Toxoplasmosis
3. Congenital rubella syndrome

• Drugs

1. Fetal hydantoin syndrome
2. Fetal alcohol syndrome

Other

1. Radiation exposure to mother
2. Maternal malnutrition
3. Maternal phenylketonuria
4. Poorly controlled gestational diabetes
5. Hyperthermia
6. Maternal hypothyroidism
7. Placental insufficiency

Postnatal onset

Genetic

• Inborn errors of metabolism

1. Congenital disorder of glycosylation
2. Mitochondrial disorders
3. Peroxisomal disorder
4. Glucose transporter defect
5. Menkes disease
6. Congenital disorders of amino acid metabolism
7. Organic acidemia

Syndromes

• Contiguous gene deletion

1. 17p13.3 deletion (Miller–Dieker syndrome)

• Single gene defects

1. Rett syndrome (primarily girls)
2. Nijmegen breakage syndrome
3. X-linked lissencephaly with abnormal genitalia
4. Aicardi–Goutières syndrome
5. Ataxia telangiectasia
6. Cohen syndrome
7. Cockayne syndrome

Acquired

• Disruptive injuries

1. Traumatic brain injury
2. Hypoxic-ischemic encephalopathy
3. Ischemic stroke
4. Hemorrhagic stroke

• Infections

1. Congenital HIV encephalopathy
2. Meningitis
3. Encephalitis

• Toxins

1. Lead poisoning
2. Chronic renal failure

• Deprivation

1. Hypothyroidism
2. Anemia
3. Congenital heart disease
4. Malnutrition

A genetic factor may play a role in causing some cases of microcephaly. Relationships have been found between autism, duplications of chromosomes, and macrocephaly on one side. On the other side, a relationship has been found between schizophrenia, deletions of chromosomes, and microcephaly. Moreover, an association has been established between common genetic variants within known microcephaly genes (MCPH1, CDK5RAP2) and normal variation in brain structure as measured with MRI (i.e., primarily brain cortical surface area and total brain volume).

Microencephaly

"Microcephaly" means "smallheadedness" (New Latin microcephalia, from Ancient Greek μικρός "small" and κεφαλή "head"). "Microencephaly" means "small brain". Because the size of the brain is mostly determined by the size of the head, microencephaly is implied when discussing microcephaly.

Other

After the dropping of atomic bombs on Hiroshima and Nagasaki, several women close to ground zero who had been pregnant at the time gave birth to children with microcephaly. Microcephaly prevalence was seven of a group of 11 pregnant women at 11–17 weeks of gestation who survived the blast at less than 1.2 km from ground zero. Due to their proximity to the bomb, the pregnant women's in utero children received a biologically significant radiation dose that was relatively high due to the massive neutron output of the lower explosive-yielding Little Boy. Microcephaly is the only proven malformation, or congenital abnormality, found in the children of Hiroshima and Nagasaki.

Prognosis

Generally, no specific cure is known for microcephaly. Treatment is symptomatic and supportive.

History

People with microcephaly were sometimes sold to freak shows in North America and Europe in the 19th and early 20th centuries, where they were known by the name "pinheads". Many of them were presented as different species (e.g., "monkey man") and described as being the missing link. Famous examples are Zip the Pinhead (although he may not have had microcephaly) and Schlitzie the Pinhead, who also starred in the 1932 movie Freaks. Both these individuals were cited as influences on the development of the long-running comic strip character Zippy the Pinhead, created by Bill Griffith.

Notable cases

• Triboulet was a jester of duke René of Anjou (not to be confused with the slightly later Triboulet at the French court).
• Jenny Lee Snow and Elvira Snow, commonly referred to as Pip and Flip, were sisters with microcephaly who acted in the 1932 film Freaks.
• Schlitze "Schlitzie" Surtees, possibly born Simon Metz, was a sideshow performer and actor.
• Lester "Beetlejuice" Napoleon Green known on the Howard Stern Show for being " The Greatest Wack Packer of All Time"

See also

• Hydrocephaly
• Macrocephaly
• Seckel syndrome
• Anencephaly

External links

• microcephaly at NINDS
• Microcephaly Support Group
• The Rat People of Pakistan
• NINDS Overview
• Schlitzie The Pinhead