1p36 deletion syndrome

Overview

1p36 deletion syndrom is a typical severely mentally retarded disorder caused by a deletion of the 1p36 region at the end of the short arm of chromosome 1.

Epidemiology

1p36 deletion syndrome is estimated to occur in 1 in 5 000 to 10 000 newborns. However, this may be an underestimate, as it is thought that some affected individuals may never be diagnosed.

Cause

The 1p36 deletion syndrome is caused by the deletion of genetic material from a specific region of the short arm (p) of chromosome 1. Signs and symptoms of the 1p36 deletion syndrome are probably related to the loss of several genes in this region. The size of the deletion depends on the affected individual.

Most cases of 1p36 deletion syndrome are not inherited. It is caused by a random chromosomal deletion that occurs during the formation of germ cells (oocytes or sperm) or early in foetal development. Usually, affected individuals have no family history of the disease.

About 20% of people with 1p36 deletion syndrome inherit the chromosome with the deleted part from an unaffected parent. In these cases, the parent has a chromosomal rearrangement called an equilibrium translocation, which means that there is no increase or decrease in genetic material. Equilibrium translocations do not usually cause health problems, but they can become imbalanced when passed on to the next generation. Children who inherit an imbalanced translocation may develop chromosomal rearrangements containing extra or missing genetic material; people who inherit an imbalanced translocation in 1p36 deletion syndrome have missing genetic material from the short arm of chromosome 1, resulting in birth defects and other health problems characteristic of this disorder. The result is the birth defects and other health problems characteristic of this disorder.

Symptoms

Most patients do not speak or speak only a few words. They may also throw tantrums, bite and exhibit other behavioural problems. There is also a structural brain abnormality, which causes seizures in more than half of them. They also usually have weak muscle tone (hypotonia) and difficulty swallowing.

Patients with 1p36 deletion syndrome are characterised by a small head, abnormally short and wide for its size (microcephaly). Facial features also include deep eyes, straight eyebrows and a hollow middle face (midfacial hypoplasia), a wide, flat nose with a long space between the nose and mouth (palatoplasty), a pointed chin, low, backwardly rotated ears and an abnormal shape.

People with 1p36 deletion syndrome may have problems with vision and hearing. Others may have abnormalities of the skeleton, heart, digestive system, kidneys or reproductive organs.

Diagnosis

Cytogenetic analysis: detection of deletion of 1p36 on the short arm of chromosome 1

In addition to characteristic facial features (straight eyebrows, deep eyebrows, receding midface, wide and low nasal ridge, long median, pointed chin), microcephaly, short head, luxated internal eye angle, large (larger than 3 cm at birth) macrosomia, delayed macrosomia closure, and low, posteriorly inclined and morphologically abnormal auricles are also present.

Treatment

There is no fundamental cure. However, early diagnosis and individualised rehabilitation therapy focusing on motor development, cognition, communication and social skills may help alleviate symptoms.

Congenital heart disease may resolve spontaneously or require drug therapy or surgery. Epileptic seizures are treated with standard anti-epileptic drugs.

Treatment with anticonvulsants may be effective for childhood seizures.

Feeding difficulties are common and feeding and growth should be monitored.