Managing The Symptoms of Nijmegen Breakage Syndrome - An overview

Introduction

Nijmegen breakage syndrome (NBS), is a genetic disorder that is characterized by certain features at birth, along with a deficiency in immunity and risk of cancers. It is a rare condition occurring due to chromosomal instability. Diagnosis depends on clinical features and genetic testing. Anti-microbial therapy for infections, immunoglobulin replacement therapy, cellular vaccines, and specific symptomatic treatment can be done. Symptoms, diagnosis, and treatment are explained in this article.

What Is Nijmegen Breakage Syndrome?

Nijmegen breakage syndrome is an autosomal recessive syndrome characterized by a small size of the head at birth, a decrease in immunity, and a high risk of cancer. The symptoms are similar to other diseases, such as DNA (deoxyribonucleic acid) ligase deficiency and severe combined immunodeficiency syndrome.

Differentiation between NBS (Nijmegen breakage syndrome) and other disorders can be done by genetic testing.

What Are the Symptoms of Nijmegen Breakage Syndrome?

• Growth Deficiency: Infants are born with below-normal weight along with a head circumference less than normal. The ratio of the head to the whole body may be varied as the growth is retarded. Growth deficiency can occur up to two years of life and after which the linear growth velocity becomes normal.

• Infections of the Respiratory Tract: Bronchitis (inflammation of the lung lining) and recurring pneumonia (recurring infection in the lungs) can result in pulmonary failure and even death.

• Malignancy: Malignancy can be developed even before 20 years of age. Lymphoma, mostly B cell-related rather than T cell, can also occur. The second malignancy can develop, or the primary malignancy can relapse depending on the individual clinical condition.

• Decrease in Intellectual Abilities: The intelligence quotient is normal during the first phase, and the intellectual abilities keep declining from mild to moderate as the child grows.

• Fertility: Hypogonadism (failure of functioning of gonads) can be present in most of the affected females rather than males. Ovarian failure can be seen in females.

• Urinary tract infections can also occur.

• The frequency of infections in immune-compromised patients is higher than compared to normal individuals. Community-acquired pathogens usually cause most of the infections; only 5 % are due to opportunistic infections.

• Microcephaly (smaller than usual circumference of the head).

How Is Nijmegen Breakage Syndrome Diagnosed?

Diagnosis of the syndrome Nijmegen breakage syndrome is made based on the following criteria:

• Clinical symptoms.

• Chromosomal instability.

• Immunodeficiency.

• Increased cellular sensitivity.

Diagnosis is made early to avoid the following:

• Recurrent infections can be avoided by following appropriate prophylaxis.

• To avoid unnecessary exposure to radiation.

• To avoid radiotherapy adverse reactions in treating malignant tumors.

Clinical Symptoms:

• Frequent respiratory tract infections.

• Malignancies.

• Prominent midface.

• Ovarian insufficiency.

• Lack of neurological symptoms.

Genetic Analysis: It helps confirm the diagnosis acquired through clinical symptoms. The final diagnosis is acquired by cytogenic and molecular genetics.

What Are the Circumstances to Be Avoided?

As the cells of the individual suffering from this syndrome are radio-sensitive, radiation doses in radiotherapy must be reduced. Magnetic resonance imaging and ultrasound are considered in places of ionizing radiation, such as plain radiography and CT (computed tomography) scans in imaging studies. Live vaccines should not be given.

What Is the Management for Nijmegen Breakage Syndrome?

The following are the treatment manifestations:

• Anti-microbial therapies.

• Immunoglobulin replacement therapy.

• Acellular vaccines.

• There is no specific therapy present. As immunodeficiency is present in patients suffering from Nijmegen breakage syndrome, a multi-disciplinary approach to management is necessary, along with long-term follow-up. Female patients are under the care of a gynecologist during the pubertal age.

• Treatment of Immunodeficiency:

1. Maintaining the immune system is highly essential throughout the life of an individual, especially in the case of patients suffering from the syndrome. Just evaluate the peripheral blood immune biomarkers at the time of diagnosis as well as in the follow-ups.

2. This assessment is performed once a year in patients with good clinical condition and patients with immunity deterioration time. The follow-up is done every three to four months.

3. The patient should not be vaccinated with live viral or bacterial vaccines.

• Treatment of Malignancy:

1. Staging of the malignancy is done to design a proper treatment protocol for the patients suffering from malignancy. This syndrome is associated with treatment-related toxicity. Sepsis (release of chsmicals into blood stream) can occur in patients suffering from this syndrome, and death due to cardiomyopathy (difficulty in the heart to supply blood) can also occur.

2. Modifications in the treatment through chemotherapy can be done by limiting the dose of the medication and even avoiding certain agents.

3. Treatment outcome was feasible and manageable complications occurred when chemotherapy of a dose greater than 80 percent was administered.

• Speech Therapy:

1. Delayed development of speech was observed in most of the children, and correction of articulation problems required speech therapy.

2. A psychological assessment is done periodically every year to check for development in a child's intelligence quotient.

• Surveillance:

1. Regular periodic follow up for maintaining the physical growth progress and development of infection frequency should be done along with monitoring of immune markers for life. When hormone replacement therapy is administered, a monthly breast examination is advised regularly.

What Is Genetic Counseling?

The direct child's parents serve as obligate carriers of mutations in the syndrome. There is a 25 % chance in every pregnancy that the fetus has. Heterozygous carriers are asymptomatic. However, cancer risk is increased in the carriers.

What Is the Prognosis of Nijmegen Breakage Syndrome?

The prognosis is poor in patients suffering from Nijmegen breakage syndrome. Patients with b cell lymphoma have better cures and prognoses as compared to T-cell lymphoma. Monitoring of gammopathy is necessary as it is useful in the diagnosis of serious complications. As immune system correction can help in preventing the development of other malignancies, hematopoietic stem cell transplantation can also be considered.

Conclusion

Deficiencies in DNA (deoxyribonucleic acid) repair occurs in certain human disorders that help establish a network in cellular responses. The causes of the disease were identified, which paved the way for determining the proper treatment plan to reduce the negative consequences of the treatment. For instance, radiation of both therapeutic and diagnostic types is avoided. Examining defects in patients suffering from this syndrome leads to developing strategies. Identification of the genes in such a syndrome can help in improving the prognosis.