Cohen's syndrome: what is it, causes, symptoms, treatment, prognosis

What is Cohen's Syndrome?

Cohen's syndrome is a fairly variable genetic disorder characterized by decreased muscle tone (hypotension), disorders of the brain, face, hands and feet, visual impairment and non-progressive mental backwardness. Patients usually have microcephaly, a condition indicating that the head circumference is smaller than would be expected for the age and sex of the child.

Many elderly patients have obesity, especially around the torso, while the arms and legs are thin. Some people have low levels of certain white blood cells known as neutrophils (neutropenia) from birth.

Cohen's syndrome is an autosomal recessive genetic disorder caused by mutations in a gene VPS13B / COH1.

Signs and symptoms

The signs and symptoms of Cohen's syndrome can vary from one person to another. Although researchers have been able to establish a clear syndrome with characteristic or “core” features, much about the disorder is not fully understood. Several factors, including the small number of case reports and the lack of large clinical trials, prevent clinicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms described below. Parents should speak with their children's doctor and medical team about their specific case, associated symptoms, and overall prognosis.

Newborns with Cohen's syndrome usually have decreased muscle tone (hypotension). Due to hypotension, feeding and breathing problems may be present in the early days of life. Some newborns may have a faint or high-pitched cry. Some children may have an inability to gain weight and grow, as would be expected depending on gender and age (inability to develop). A child's joints can be “loose”, which means they have an unusually large range of motion (joint hypermobility). Microcephaly of mild to moderate severity often develops during the first year of life and continues into adulthood.

As infants get older, they may show delays in achieving normal developmental skills such as sitting or rolling over. The extent of such delays varies greatly, even among members of the same family. Walking is often delayed for up to 2-5 years. Delays in speech are also common; the child's first words or the child's ability to speak or pronounce in sentences are often delayed.

Mild to moderate intellectual disability does not progress, and affected people demonstrate the ability to learn new concepts. Most children are described as outgoing with a cheerful disposition. In some cases, children may show behavioral problems related to autism spectrum. Although epilepsy was rare, in some people it is present.

During childhood, often around the age of 5, distinctive facial features may appear. Such features include:

• big ears;
• noticeable root of the nose (the part of the nose between the eyes);
• low hairline;
• Highly bulging or wavy eyelids
• long, thick eyelashes;
• thick eyebrows;
• high, narrow roof of the mouth (palate);
• an abnormally short groove in the middle of the upper lip (groove);
• prominent upper central incisors.

Some people may develop recurrent small, round mouth ulcers (aphthous ulcers) and develop inflammation or infection of the gums (gingivitis). In the medical literature, the range of distinctive facial features (see. (see photo above) is highly variable, and specific traits appear to be more common in individuals of a particular ethnic background.

Affected people often develop various disorders affecting the eyes and may experience vision problems in early childhood. Such violations include:

• decreased visual acuity;
• myopia;
• strabismus.

Myopia usually gets worse throughout childhood.

Those affected may also have chorioretinal dystrophy, a condition characterized by abnormalities affecting the choroid and retina, including retinal degeneration. The choroid is the middle layer of the eye, made up of blood vessels that supply blood to the retina. The retina is a membrane layer of light-sensitive cells at the back of the eye, converting light into specific nerve signals, which are then transmitted to the brain to form images.

Chorioretinal dystrophy is progressive and can lead to poor vision in low light and eventually night blindness (nyctalopia) and decreased visual field with decreased ability to see left or right when looking straight ahead (narrowing of the peripheral field vision; sometimes referred to as tunnel vision). Loss of peripheral vision can cause people to stumble or fall easily.

Less commonly, additional eye abnormalities associated with Cohen's syndrome include:

• abnormal curvature of the cornea (astigmatism);
• reduction in the size of the cornea (microcornea);
• abnormally small eyeballs (microphthalmia);
• clouding (opacity) of the lenses;
• degeneration of the iris (iris atrophy);
• degeneration of the optic nerve that carries impulses from the eyes to the brain (optic atrophy);
• cleft of missing tissue (coloboma) in the retina or eyelids.

Some develop obesity of the trunk that occurs in mid-childhood. The arms and legs may remain thin. People can be below average height for their age and gender. Some patients may have small, thin arms and legs. Delayed puberty has also been reported and some men have undescended testes (cryptorchidism).

Abnormal curvature of the spine is common. Affected people may develop abnormal curvature of the spine in the front and back (kyphosis) or a combination of kyphosis with pathological curvature of the spine to the side (scoliosis).

People with Cohen's syndrome may have a condition called neutropenia, in which there are abnormally low levels of certain white blood cells called neutrophils. Neutrophils are needed by the body to fight off infections by surrounding and destroying bacteria that enter the body from outside. Episodes of neutropenia are usually mild to moderate. Some people may experience recurrent infections, such as respiratory infections or minor skin infections. Children with Cohen's syndrome may be prone to developing middle ear infections (otitis media). Chronic development of aphthous ulcers and gingivitis may be due in part to neutropenia.

Individuals with Cohen's syndrome are at increased risk of developing autoimmune diseases, diabetes mellitus, as well as thyroid diseases and celiac disease. Autoimmune disorders occur when the body's immune system mistakenly attacks its own healthy tissue.

Causes

Cohen's syndrome is caused by changes in a gene COH1. This gene is also known as the gene VPS13B. Genes provide instructions for making proteins that play important roles in many bodily functions. When a gene change occurs, the protein product may be defective, ineffective, or missing. Depending on the functions of a particular protein, it can affect many organ systems in the body.

Changes COH1 the gene in Cohen's syndrome is inherited in an autosomal recessive manner. Most genetic diseases are determined by the status of two copies of a gene, one from the father and the other from the mother. Recessive genetic disorders occur when a person inherits two copies of an altered gene for the same trait, one from each parent. If a person inherits one normal gene and one altered gene for a disease, the person will carry the disease but will not show symptoms. The risk for two carrier parents who both pass on the altered gene and infect the baby is 25% with each pregnancy. The risk of giving birth to a carrier child, like the parents, is 50% with each pregnancy. The risk for a child to receive normal genes from both parents is 25%. The risk is the same for men and women.

Researchers have determined that the protein product of the gene COH1 participates in glycosylation, the process by which sugar trees (glycans) are created, modified and chemically bound to certain proteins or fats (lipids). When these sugar molecules are attached to proteins, they form glycoproteins; when attached to lipids, they form glycolipids. Glycoproteins and glycolipids perform many important functions in all tissues and organs. Glycosylation includes many different genes that encode many different proteins, such as enzymes. A deficiency or deficiency in one of these enzymes can lead to a variety of symptoms potentially affecting multiple organ systems, and there is almost always an important neurological component. Symptoms can vary in severity.

Affected populations

Cohen's syndrome affects men and women in approximately equal numbers. Apparently more common in people of Finnish, Amish, Greek / Mediterranean, and Irish descent. More than 150 cases have been reported in the medical literature and approximately 500-1000 people have been diagnosed with the disorder worldwide. However, cases of Cohen's syndrome often go undiagnosed or misdiagnosed, making it difficult to determine the true incidence of the disorder in the general population.

Related disorders

Symptoms of the following disorders may be similar to those of Cohen's syndrome. Comparisons can be useful for differential diagnosis:

• Prader-Willi syndrome (ADD) is a genetic multisystem disorder characterized by lethargy, decreased muscle tone (hypotension), nutritional problems, and poor weight gain in childhood. In childhood, features of this disorder include short stature, small genitals, and excessive appetite because those affected do not feel satisfied after completing a meal (satiety). Without intervention, this can lead to overeating and gradual obesity. Food compulsion requires constant monitoring. Severely obese people may be at increased risk heart failure, sleep apnea, diabetes and other serious conditions that can cause life-threatening complications. All people with ADD have some cognitive impairment that ranges from low normal intelligence with learning disabilities to mild to moderate mental retardation. Behavioral problems are common and can include outbursts of anger, obsessive / compulsive behavior. Motor skills and language development are often delayed. ADD occurs due to changes that affect certain genes in a specific region of chromosome 15. These deviations are usually the result of random (sporadic) developmental errors, but are sometimes inherited.
• Angelman syndrome - a rare genetic neurological disorder characterized by severe developmental delays and learning disabilities; lack or almost no speech; an inability to coordinate voluntary movements (ataxia) and trembling, jerky movements of the arms and legs; and distinct behaviors characterized by a happy disposition and unprovoked episodes of laughing and smiling, often at the wrong time. Although affected people may be unable to speak, many gradually learn to communicate through other means, such as gestures. In some cases, additional symptoms may occur, including epilepsy, sleep disturbances, and eating problems. Some affected children may have distinctive facial features.

Certain other genetic disorders can have signs and symptoms that are similar or identical to those seen in Cohen's syndrome. These disorders include Alstrom syndrome, Cree du Chat syndrome, Williams syndrome, Bardet-Beadl syndrome, and hypothyroidism.

Diagnostic methods

An accurate diagnosis of the disease requires characteristic clinical tests along with molecular genetic testing for mutations in the gene. VPS13B.

Standard treatments

Treatment for Cohen's syndrome focuses on the specific symptoms that each person experiences. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, pediatric neurologists, orthopedists, ophthalmologists, psychiatrists, speech therapists and other medical workers may need systematic and comprehensive planning of the victim's treatment child.

The treatment options that can be used to treat people with Cohen's syndrome are complex and varied. The specific treatment plan should be highly personalized. Decisions regarding the use of specific treatments should be made by doctors and other team members. health care in close consultation with the parents of a sick child or with an adult patient on the basis of the specifics case; careful discussion of potential benefits and risks, including possible side effects and long-term consequences; patient preferences; and other relevant factors.

Early developmental intervention is important to ensure that affected children reach their potential. Most affected children will benefit from occupational, physical and speech therapy. Various methods of rehabilitation and behavioral therapy will also be helpful. Additional medical, social and / or professional services may be required, including special remedial education. Psychosocial support for the entire family is also needed.

Specific treatments for Cohen's syndrome include wearing glasses and lenses to help with vision. In subsequent years, people with visual impairments need gymnastics for their vision. Recurrent infections can be treated with standard therapy, including antibiotics.

In some cases, neutropenia can be treated with granulocyte colony stimulating factors (G-CSF). G-CSF is an industrial version of natural hormones that stimulate the bone marrow to produce neutrophils. G-CSF increases the number of neutrophils generated by the bone marrow and increases the effectiveness of their ability to kill bacteria.

Forecast

Life expectancy does not decrease, but the quality of life is reduced due to visual impairment.