Wolf-Hirschhorn syndrome: causes, symptoms, treatment, prognosis

What is Wolf-Hirschhorn Syndrome?

Wolff-Hirschhorn syndrome (abbr. Temporary storage warehouse or also called partial monosomy 4p-) is an extremely rare chromosomal disorder caused by the absence of a fragment (partial removal or monosome) of the short arm of chromosome 4. The main symptoms may include extremely wide-set eyes (ocular hypertelorism), wide or beak-like nose, small head (microcephaly), low-set ears, small stature, weight, heart defects, mental backwardness and epilepsy. Symptoms of the disease vary from person to person, depending on the size and location of the missing fragment of chromosome 4.

Signs and symptoms

The manifestations of the Wolf-Hirschhorn syndrome in each patient can vary greatly. The most distinctive feature of the temporary storage warehouse is the typical facial appearance. People with the condition usually have a widening and bulging area in the upper part of the nose between the eyebrows (glabella). It is characterized by prominent, wide-set eyes, arched eyebrows, and a small lower face, including a short upper lip, small mouth, and jaw.

Signs that are present in almost all people with SVH include:

• pronounced growth problems (both short and low weight), beginning before birth and resistant to intervention;
• intellectual retardation (variable, but often quite pronounced);
• a state of decreased muscle tone (muscle hypotonia);
• epilepsy.

Other common symptoms of the disease include:

• small head (microcephaly);
• eye abnormalities (drooping eyelids, eye malformations);
• ear abnormalities (small, low-set ears);
• cleft lip and cleft palate (heiloschisis);
• abnormalities of the penis, testicles, or vagina;
• kidney abnormalities;
• bone problems;
• dental problems.

Congenital heart defects are common in patients with SVH, but they are usually quite mild, such as a hole between two upper chambers of the heart (atrial septal defect or ASD), and can be resolved with surgical interference.

Many sufferers are at increased risk of infection. Some are immunocompromised, most often a reduced ability to make antibodies.

Feeding problems are extremely common and can be quite serious. Most sick children need artificial feeding, and many need this throughout their lives. Some people have serious bowel problems, including malrotation (a birth defect in the bowel that increases the risk of bowel twisting and interruption of blood supply), intestinal obstruction or poor bowel ability to absorb nutrients.

Intellectual disability and developmental problems are variable, but quite pronounced for most patients with the disease. Patients experience problems in all areas, including:

• communication;
• gross motor skills;
• fine motor skills;
• quantitative reasoning.

Bowel and bladder control is usually delayed until late childhood and sometimes not achieved. Most people need to facilitate communication through speaking devices or sign language.

Initially, Pitt-Rogers-Danks Syndrome (PITS) was described as a separate disorder of Wolff-Hirschhorn Syndrome (SVS). However, patients with SPDD ultimately also showed deletions (loss of a portion) of the short arm of the 4th chromosomes in the same region associated with SVH, so this condition is now believed to be milder forms of temporary storage warehouse.

Causes and risk factors

Wolff-Hirschhorn syndrome results from the deletion of genetic material at the end of the short (p) arm of chromosome 4.

Chromosomes are found in the nucleus of all cells in the body. They carry the genetic characteristics of every person. Pairs of human chromosomes are numbered from 1 to 22, the 23rd pair consists of chromosomes X and Y, XX is associated with the female sex, and XY with the male. Each chromosome has a short arm (shoulder), denoted by the letter "p" and a long arm, denoted by the letter "q". Chromosomes are further subdivided into numbered bands. For example, “chromosome 4p16.3” refers to band 16.3 on a short stretch of chromosome 4. The numbered stripes are used to locate the genes found on each chromosome.

The absence of part of the short arm of chromosome 4 (4p) causes this disorder. It is believed that part of the 16.3 band on chromosome 4p (4p16.3) is the "critical region" for this disorder; removal of this area leads to the full manifestation of the Wolf-Hirschhorn syndrome.

In most patients, the loss of the chromosome region that causes the disease occurs at an extremely early stage of development. a person (possibly in an egg or sperm before fertilization) and is not inherited from parents (i.e. there is spontaneously). Much less often, the disease is inherited from a parent who has a balanced translocation.

A translocation is a type of chromosomal mutation in which different chromosomes exchange their fragments. If all the parts of both chromosomes involved in the exchange are present, this is called a "balanced" translocation. Because a person with a balanced translocation has all the necessary genetic material for normal development, they usually have no health problems associated with their mutated chromosome. Unfortunately, a balanced translocation can be passed on to a child in an unbalanced manner, resulting in a lack of or additional genetic material in a child and causes a chromosomal disorder such as syndrome Wolf-Hirschhorn.

Affected populations

SVH is an extremely rare disease. Research from about 25 years ago showed that the disorder occurred in about 1 in 50,000 live births with a 2: 1 female to male ratio. More recent research has shown that the incidence of the disorder can be underestimated due to misdiagnoses.

Diagnostics

Signs of Wolff-Hirschhorn syndrome can be detected by ultrasound examination (ultrasound) while the child is still is in the womb, or due to the characteristic appearance of the face, growth disorders, developmental delays and seizures after childbirth. Distinctive facial features are usually the first clue that a child has the condition. Genetic testing is needed to confirm the diagnosis.

If an illness is suspected during pregnancy, genetic testing can also be done, as well as a more sophisticated test called fluorescence in situ hybridization (or FISH).

Additional tests, such as X-ray results for the study of bone and internal malformations, renal ultrasound diagnostics for kidney examinations as well as magnetic resonance imaging (MRI) of the brain can help determine the range of symptoms that may be encountered child.

Symptomatic Disorders

Syndromes involving deletions of other chromosomes may be similar to Wolff-Hirschhorn syndrome. Comparisons can be useful for differential diagnosis.

Chromosomal Disordersthat include additional chromosomes (trisomy) have some similarities (in particular, impaired growth and a noticeable effect on development) with Wolf-Hirschhorn syndrome (SVS). These disorders include Patau syndrome (trisomy 13) and Edwards syndrome (trisomy 18).

Screaming syndrome - a congenital chromosomal disorder involving partial removal of chromosome 5. It may also overlap with SVH, including poor growth, small head, nutritional problems, and intellectual disabilities. People with the disorder have breathing and airway problems and a loud, high-pitched cry. Patients with crying syndrome have distinct facial features that are different from those seen in SVH.

Down Syndrome - a congenital chromosomal disorder involving three copies of chromosome 21. The main symptoms are distinctive facial features (different from those seen in patients with Wolff-Hirschhorn syndrome), low muscle tone, short stature, and mental retardation. Serious birth defects such as heart defects and gastrointestinal abnormalities are also common.

Angelman syndrome characterized by severe developmental delay, mental retardation, severe speech impairment, posture and motor problems, microcephaly, and seizures (epilepsy). Angelman syndrome is caused by abnormalities in the q11.2-q13 region of chromosome 15.

Williams Syndrome (elf face syndrome) is characterized by mild mental retardation, distinctive facial features, and cardiovascular disease. Due to the accumulation of calcium in different parts of the body, kidney and digestion problems can occur.

Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency) is characterized by growth retardation, small head, mental disabilities, distinctive facial features, heart defects, and an underdeveloped penis and testicles in men.

Treatment of the Wolf-Hirschhorn syndrome

Since there is no cure for treating a birth defect once it occurs, treatment for Wolff-Hirschhorn syndrome aims to address a variety of symptoms. Patients with a known or suspected diagnosis of SVH symptoms should undergo a comprehensive evaluation by an experienced geneticist. Most patients will need to be accompanied by several specialists.

Patients should undergo a neurological examination with an assessment of epileptic seizures, detailed cardiac (cardiac) monitoring, eye examinations, hearing examinations, kidney function, nutrition and development as soon as possible after staging diagnosis.

Kidney function should be monitored on an ongoing basis. All patients should be provided with comprehensive developmental and rehabilitation assistance, including: feeding, assisted communication, speech, physical therapy, occupational therapy, and school support.

Forecast

Wolf-Hirschhorn disease is associated with frequent stillbirths, perinatal mortality, and death within the first year of life. If patients survive after infancy, their neurological development progresses slowly but steadily.