Megalencephaly

Megalencephaly is a condition in which an infant or child develops an unusually heavy and large brain for their age and gender. The condition is often present at birth but may develop over time. The condition can occur alone without any symptoms or in conjunction with a wide range of other birth defects or neurological problems.

Definition & Facts

The Office of Rare Disorders division of the National Institutes of Health classifies megalencephaly as a rare disease. This means that the condition affects less than 200,000 people in the United States. The average adult brain weighs between 2.87 and 3.09 pounds. The brain of an individual with megalencephaly typically weighs more than 3.53 pounds and can even reach twice the normal size. Megalencephaly is classified according to three broad categories:

• Primary megalencephaly, also known as benign familial megalencephaly.
• Secondary megalencephaly, which is the direct result of another disorder.
• Hemimegalencephaly, also known as unilateral megalencephaly, in which only half of the brain is enlarged. This form of megalencephaly is associated with the most severe symptoms and disability.

Megalencephaly is sometimes confused with macrocephaly, in which the head is enlarged but not necessarily abnormal. Macrocephaly refers to an enlarged head resulting from any cause, including a skeletal anomaly or excess fluid (hydrocephalus). Megalencephaly, on the other hand, involves an enlarged head as well as a “heavy” brain suggesting abnormal brain structure and function.

The National Institute of Neurological Disorders and Stroke and other divisions of the National Institutes of Health are currently conducting research into megalencephaly. Additional research efforts are also underway at various institutions around the country in the hopes of better understanding the complex processes of brain development. The information gleaned from these studies may one day lead to the development of ways to prevent cephalic disorders, including megalencephaly.

Symptoms & Complaints

In some cases, megalencephaly can cause the facial features to have an abnormal shape or size. Severe cases of megalencephaly are often associated with cognitive impairment, seizures, and other neurological symptoms. This is especially common in cases of hemimegalencephaly. Neurological symptoms of megalencephaly include:

• Lack of gross motor skills, which can make it difficult for the individual to hold their head upright, stand, sit, or otherwise change positions.
• Lack of muscle tone.
• Delayed speech development.
• Dysfunction of the spinal cord, which can lead to paralysis and an inability to control movements.
• Body asymmetry.
• Vision problems.

The exact prevalence of megalencephaly is unknown since asymptomatic cases may go unreported; however, it is believed that the condition is three to four times more likely to affect males than females. The condition may also affect up to 30 percent of individuals with macrocephaly.

Causes

Megalencephaly is believed to be linked to a defect in the way in which the brain controls nerve cell production, also called neuron proliferation. During normal development, the process in which cells divide to form new cells is well regulated so that the appropriate number of cells is produced in the right place at the right time. In individuals with megalencephaly, these cells over-produce during the development process or as a result of another disorder.

Genetic disorders that can contribute to megalencephaly include Alexander disease, Klinefelter syndrome, Sotos syndrome, Beckwith-Wiedemann syndrome, tuberous sclerosis, and neurofibromatosis.

A buildup of metabolic byproducts and disorders affecting the cerebrospinal fluid may also cause megalencephaly. In some cases, the condition is idiopathic and cannot be linked to a specific causative factor.

Diagnosis & Tests

The diagnosis of megalencephaly typically starts with a physical examination that includes measuring the circumference of the head. A detailed family history and head measurements of immediate family members can be beneficial in identifying cases of benign familial megalencephaly.

Magnetic resonance imaging (MRI) scans and computed tomography (CT) scans may be used to get detailed pictures of the brain so that the doctor can get a better idea of the size and appearance of the various brain structures. Medical ultrasounds and MRIs allow for a growing number of megalencephaly cases to be diagnosed prenatally.

Developmental and neurological examinations may be required if there is evidence of cognitive or physical developmental delays or neurological problems. Laboratory tests may be used to help identify the underlying cause of the condition, including genetic and chromosomal disorders.

Treatment & Therapy

There is currently no treatment or cure for megalencephaly. Treatments are largely aimed at controlling or minimizing associated symptoms and vary depending on the underlying cause of the condition. For example, anti-epileptic medications may be prescribed to minimize and control seizures.

Unfortunately, these medications are often ineffective in patients with hemimegalencephaly. These patients often require surgery to bring their seizures under control. This involves either an anatomical or functional hemispherectomy. In an anatomical hemispherectomy, the affected side of the brain is surgically removed. In a functional hemispherectomy, the affected portion of the brain is disconnected from the other brain structures. In most cases, the remaining part of the brain will gradually assume the functions normally performed by affected side.

Speech therapy, occupational therapy, and physical therapy may be useful in managing the physical and neurological effects of the condition. Children with cognitive deficits related to megalencephaly may require special education classes.

Prevention & Prophylaxis

The long-term prognosis and overall quality of life for someone with megalencephaly depend on the severity of the symptoms. In some instances, the symptoms are so mild that they have little impact on daily life. For other patients, especially those with hemimegalencephaly, the cognitive impairment, seizures, and paralysis are so severe that they dramatically limit daily functioning.