Borjeson-Forssman-Lehmann Syndrome - Symptoms, Diagnosis, and Treatment

Introduction:

Syndrome denotes a group of several signs and symptoms. They are mostly genetic in origin. A change in a specific part or complete gene may result in genetic disorders. Moreover, the affected parent may pass the defective genes to their young ones. One such genetic disorder is Borjeson-Forssman-Lehmann syndrome. This article describes in detail its signs, symptoms, diagnosis, and treatment.

What Is Borjeson-Forssman-Lehmann Syndrome?

Borjeson-Forssman-Lehmann syndrome is an inherited disorder that causes obesity, intellectual disabilities, facial abnormalities, and developmental delays. The affected individual does not possess the same symptoms and signs as others, which means that the symptoms may vary. In addition, males are more severely affected than females.

How Does a Person Get Borjeson-Forssman-Lehmann Syndrome?

Each cell in our body carries genetic material called DNA, and genes are a part of it, which is greatly essential in giving proper instructions for protein production. All the organs in our body require these proteins to maintain their structure and function. Therefore, any change (mutation) in the genes may result in organ abnormality both structurally and functionally.

Likewise, the Borjeson-Forssman-Lehmann syndrome is caused by a change in a specific gene called PHF6 (plant homeodomain finger 6). The PHF6 gene is responsible for producing a protein that maintains the proper functioning of neurons in the brain and prevents cancer, as it is found in some immune cells (T-lymphocytes). Therefore the mutated gene may also be found in individuals with certain types of cancer (T-cell leukemia).

Moreover, the Borjeson-Forssman-Lehmann syndrome is considered an X-linked inherited disorder, which means that the affected gene is located on the X-chromosome. The offspring acquire the disease from their affected mother; the one copy of the defective gene passed to the babies is responsible for causing the disease. However, females remain carriers of the disease (one normal and one defective X-chromosome), and males are affected with one defective X chromosome.

What Are the Signs and Symptoms?

The signs and symptoms of Borjeson-Forssman-Lehmann syndrome may vary from mild to severe.

It includes:

• Intellectual disability.

• Poor muscle tone (hypotonia).

• Truncal obesity - Excess fat accumulates in the trunk (center portion) of the body than in the extremities.

• Seizures - Abnormal brain activity that disturbs normal muscle movement, behavior, and awareness.

• Microcephaly or small head compared to other normal babies.

• Delay in attaining developmental milestones.

• Feeding difficulties.

• Impaired hearing.

Facial Abnormalities Include -

• Large earlobes.

• Prominent ridges above the eyes.

• Deep-set eyes.

• The face appears coarse due to thickened connective tissue.

• Droopy upper eyelids.

• Nystagmus (involuntary eye movements).

• Optic nerve (sends visual signals to the brain) abnormalities.

• The affected individual may suffer from hyperopia (farsightedness), a condition characterized by clouding of the eye’s lens called cataracts before 30 years of age.

Skeletal Abnormalities -

• Abnormal curvature of the spine either in the side-to-side (scoliosis) direction or in the front-to-back (kyphosis).

• The bones of toes and fingers may be underdeveloped, resulting in tapered fingers and short toes.

• Broad foot: It appears wider compared to the foot length.

• Camptodactyly of toe: The toe remains bent, and it progresses over age.

• Hip bone abnormality.

• The spinal canal may appear narrower at the cervical (neck) region.

Hormonal Abnormalities -

• In males, the testes (male sex organs) function poorly, leading to decreased production of testosterone. It results in small testicle size, enlarged breasts (gynecomastia), an underdeveloped penis, and cryptorchidism (an inability of the testes to descend into the scrotum).

• In females, there is decreased production of female sex hormones by the ovaries.

• Growth Retardation - Due to decreased hormone production of hormones, normal growth is affected, leading to short stature.

How Is Borjeson-Forssman-Lehmann Syndrome Diagnosed?

The doctor may enquire about family history and the characteristic features (facial abnormalities, truncal obesity, etc.) during the physical examination.

They may also order the following test to diagnose Borjeson-Forssman-Lehmann Syndrome:

• Radiographic Investigations - The various skeletal abnormalities and their severity are identified through plain radiographs.

• Molecular Genetic Testing - The changes or defects in particular genes can be determined using molecular genetic testing. It is a confirmatory test that detects the change in the PHF6 gene.

What Are the Related Disorders?

The following disorders have similar features to Borjeson-Forssman-Lehmann syndrome:

• Coffin-Siris Syndrome - A congenital disorder characterized by facial abnormalities like arched eyebrows, broad nasal tip, etc., and other features include developmental disability, skin hyperpigmentation, and intellectual disability. Genetic testing identifies the mutation in a specific gene that caused the disease.

• Bardet-Biedl Syndrome - Multiple body systems (kidneys, eyes, genitals, etc.) are affected by a rare genetic disorder called Bardet-Biedl syndrome. Its typical features include renal abnormalities, truncal obesity, intellectual disability, muscular abnormalities, and vision defects. Mutations in several genes are responsible for causing Bardet-Biedl syndrome. The doctor may provide treatment to relieve the patient from such symptoms.

• Prader-Willi Syndrome - The dysfunction of a specific gene in chromosome 15 is responsible for causing Prader-Willi syndrome. The classic features include feeding difficulties, poor muscle tone, and delayed development. About one in 10,000 to one in 30,000 individuals are affected by it. It may also cause facial abnormalities, sleep, and behavioral problems.

Is Borjeson-Forssman-Lehmann Syndrome Curable?

No such medications or procedures can treat Borjeson-Forssman-Lehmann Syndrome, but the healthcare specialist may suggest the following treatments to improve the patient’s symptoms:

• Anti-epileptic drugs such as Carbamazepine, Lamotrigine, etc., control seizures.

• Testosterone Replacement Therapy - The symptoms of decreased testosterone level may be improved by replacing it with testosterone available in pellet or gel form and injections.

• Nutritious Diet - A healthy diet may aid the child in coping with the situation.

• Hearing devices may aid in improving diminished hearing in a few individuals.

• The interprofessional team consists of orthopedic specialists, neurologists, pediatricians, and ophthalmologists who may plan the required treatment according to the symptoms present.

Conclusion:

Borjeson-Forssman-Lehmann syndrome is a rare acquired disorder, but it is not life-threatening. However, its features like intellectual disability, retarded growth, and skeletal abnormalities make life difficult. The affected individual may face challenges in leading a normal life. Therefore, it is the responsibility of the caretaker and healthcare specialist to improve the affected individual's physical and mental status.