About Pontocerebellar Hypoplasia

Summary of Pontocerebellar Hypoplasia

Pontocerebellar Hypoplasia is a group of related conditions that affect the development of the brain. People with these conditions have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. A region of the brain called the Pons also fails to develop properly. The Pons is located at the base of the brain in an area called the brainstem, where it transmits signals from the cerebellum to the rest of the brain.

Although the clinical features vary widely, Pontocerebellar Hypoplasia is usually associated with profound intellectual disability and delayed or absent psychomotor milestones. In most cases, the disease is uniformly fatal early in life. Life span has ranged from death in the perinatal period to about 20-25 years of age. Only a few individuals have survived to the second and third decades of life. Six forms of Pontocerebellar Hypoplasia have been identified. These forms have somewhat different signals and symptoms and different genetic causes.

Pontocerebellar Hypoplasia Type 2

In Pontocerebellar Hypoplasia Type 2 there is progressive microcephaly from birth combined with extrapyramidal dyskinesia. There is no motor or mental development. Severe chorea occurs, and epilepsy is frequent.

Characteristically, pregnancy is normal. However, at birth, the newborn may show breathing problems or respiratory failure that may require mechanical ventilatory support. Some may have sucking or feeding problems. Most people with type 2 are born with a normal size head. Some already have microcephaly at birth. All affected children have worsening or progression of the microcephaly during infancy. Other features of dysmorphisms are absent. They have impaired mental and motor development. They have abnormal movements termed extrapyramidal movement disorder. All affected children develop marked extrapyramidal dyskinetic movement disorder with predominance of dystonia. Jerky movements and almost continuous dystonic choreoathetotic movements may be seen. These movement abnormalities are usually noticed during the neonatal period of these children.

(For medical terms and definitions, refer to table below)

How will people with type 2 be affected?

People with this condition have severe to profound mental retardation. No patient with the classical type 2 ever achieved the milestones of sitting, crawling, standing, walking, talking or developed meaningful social contact skills. Visual fixation is persistently poor and only about one third of these patients are able to fixate and follow. Seizure disorder is frequent. Approximately half of these children may have seizures. A minority may also have hypotonia or hypertonia even as early as the newborn period. Minority may show spasticity.

They are severely handicapped with no voluntary motor function. The children have severe cognitive and language impairment, and with no verbal or non verbal communication.

What is the cause of type 2?

All of the recognized forms of Pontocerebellar Hypoplasia are inherited in an autosomal recessive pattern, which means both copies of the associated gene in each cell have mutations. Research has shown that mutations in three related genes, TSEN2, TSEN34, and TSEN54, can result in Pontocerebellar Hypoplasia type 2. The parents of an individual with type 2 each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Is there any treatment for type 2?

No specific therapy is available. Treatment is symptomatic and includes nutritional support by gastrostomy, treatment of seizures, and use of physiotherapy. Epilepsy is amendable to standard treatment.

Prevention of secondary complications: In type 2 monitoring and hydration during prolonged periods of high fever to avoid malignant hyperthermia.

Surveillance: In type 2 monitoring to detect sleep apnea.

How common is Pontocerebellar Hypoplasia?

The prevalence of Pontocerebellar Hypoplasia is unknown, although most forms of the disorder appear to be very rare.

Medical terms and definitions

Microcephaly	Is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person’s 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. In general, life expectancy for individuals with microcephaly is reduced and the prognosis for normal brain function is poor.
Extrapyramidal system	The extrapyramidal system is a neural network located in the brain that is part of the motor system involved in the coordination of movement. The system is called “extrapyramidal” to distinguish it from the tracts of the motor cortex that reach their targets by travelling through the “pyramids” of the medulla. The pyramidal pathways may directly innervate motor neurons of the spinal cord or brainstem, whereas the extrapyramidal system centers around the modulation and regulation (indirect control) of anterior (ventral) horn cells. Extrapyramidal tracts are found in the reticular formation of the pons and medulla, and target neurons in the spinal cord involved in reflexes, locomotion, complex movements and postural control. These tracts are in turn modulated by various parts of the central nervous system, including the nigrostriatal pathway, the basal ganglia, the cerebellum, the vestibular nuclei, and different sensory areas of the cerebral cortex. All of these regulatory components can be considered part of the extrapyramidal system, in that they modulate motor activity without directly innervating motor neurons.
Extrapyramidal dyskinesia	Any of the various movement disorders caused by disease of the extrapyramidal motor system of the brain and generally characterized by insuppressible, automatic movements that cease only during sleep.
Extrapyramidal disorder	Defects in basal ganglia function; characterized by changes in muscle tone, poverty of voluntary movements (akinesia), or abnormal involuntary movements (dyskinesia).
Chorea	Is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. Chorea is an irregular, rapid, uncontrolled, involuntary, excessive movement that seems to move randomly from one part of the body to another.
Dysmorphisms	The Dysmorphic feature is a medical term referring to a difference of body structure that is suggestive of a congenital disorder, genetic syndrome or birth defect. A dysmorphic feature can be a minor and isolated birth defect; alternatively it can be one of a combination of features signaling a serious multi system syndrome.
Dystonia	Is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth related or other physical trauma, infection, poisoning or reaction to pharmaceutical drugs, particularly neuroleptics. Treatment is difficult and ahs been limited to minimizing the symptoms of the disorder, since there is no cure available.
Choreoathetotic	Is the occurrence of involuntary movements in combination of chorea (irregular migrating contractions) and athetosis (twisting and writhing).
Malignant Hyperthermia	Malignant Hyperthermia is a rare life threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia; specifically, the volatile anesthetic agents and the neuromuscular blocking agent, succinvlcholine. In susceptible individuals, these drugs can induce a drastic and uncontrolled increase in skeletal muscle oxidative metabolism, which overwhelms the body’s capacity to supply oxygen, remove carbon dioxide, and regulate body temperature, eventually leading to circulatory collapse and death if not treated quickly.
Sleep Apnea	Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. There are three forms of sleep apnea.