About mulibrey nanism syndrome (perheentupa sy...)

What is mulibrey nanism syndrome (perheentupa sy...)?

Mulibrey nanism is an extremely rare autosomal recessive genetic disorder characterized by profound growth delays and distinctive abnormalities of the muscles, liver, brain, and eyes. The acronym MULIBREY stands for (MU)scle, (LI)ver, (BR)ain, and (EY)e. Nanism is another word for dwarfism. A characteristic feature not included in the original acronym is the overgrowth of the fibrous sac that surrounds the heart restricting normal filling of the heart (constrictive pericarditis). Characteristic symptoms may include low birth weight, short stature, and severe progressive growth delays. Muscles are usually underdeveloped and lack normal tone (hypotonia). Some infants with this disorder may have an abnormally large liver (hepatomegaly). Infants typically have yellow discoloration in their eyes.

What are the symptoms for mulibrey nanism syndrome (perheentupa sy...)?

Including a triangularly shaped face symptom was found in the mulibrey nanism syndrome (perheentupa sy...) condition

Mulibrey nanism is characterized by progressive Growth failure that begins before birth. Infants often have characteristic abnormalities of the head and face including a triangularly shaped face. Yellow discoloration deep within the eyes and other ocular abnormalities may be present but vision is usually normal. Most patients have an enlarged skull (macrocephaly) and a J-shaped sella turcica, which is a Depression in the sphenoid bone at the base of the skull. Because this is where the pituitary gland is located, individuals with MN often have underdevelopment of various endocrine glands that leads to hormone deficiencies. The voice of patients with MN is characteristically high pitched.

Patients may also have symptoms related to overgrowth of the fibrous sac surrounding the heart (non-inflammatory constrictive pericarditis). When constrictive pericarditis presents early (affecting a minority of patients), infants may have a mildly bluish discoloration of the skin (cyanosis). Congestive heart failure of the right heart can also cause abnormal fluid accumulation in the abdomen (ascites) and swelling of the arms and/or legs (peripheral edema). Circulatory problems can progress and lead to failure-to-thrive. Prominent veins in the neck indicate an elevated pressure in the systemic veins that is commonly related to a lack of space in the sac surrounding the heart (pericardial constriction) limiting the filling phase of the heart cycle, and thus leading to fluid accumulation (congestion) in the body. Fibrous tissue in the walls of the lungs (pulmonary fibrosis) decreases the total volume capacity of the lungs.

Enlargement of the liver (hepatomegaly) is another common symptom. In addition, patients often struggle to regulate the breakdown (metabolism) of sugars and fats, potentially resulting in type 2 diabetes, fatty liver and high blood pressure (hypertension). Structural abnormalities of the kidney and urinary tract such as non-cancerous pockets of membranous tissue (cysts) are also observed. However, most patients have normal kidney function. Another persistent kidney complication is a mildly decreased ability to filter the blood (glomerular filtration). Wilms’ tumor, the most common type of cancer originating in the kidney in children, is relatively common (about 8%) and screening is mandatory.

Delayed puberty sometimes occurs accompanied by infrequent or very light menstrual periods. Females have an increased risk for premature ovarian failure and tumors. Both male and female patients show failure of sexual maturation and inability of the sex organs to function properly (hypogonadism) leading to infertility.

Some individuals with MN may have additional physical abnormalities such as an unusually thin shinbone (fibrous tibia dysplasia).

Some children suffer from airway obstruction related to infections or exercise but asthma in adulthood is rare. Large cerebral ventricles in the brain and delayed motor development are uncommon findings. Most affected individuals have normal intelligence.

What are the causes for mulibrey nanism syndrome (perheentupa sy...)?

Mulibrey nanism is caused by harmful changes (pathogenic variants) in the TRIM37 gene located on chromosome 17 (17q22-q23). This gene codes for a protein present in the peroxisome, the part of cell responsible for metabolism. Loss of function of the TRIM37 protein results in a defect in the proper separation of genetic material during cell division. Normal loss of TRIM37 protein activity leads to cell death to prevent mutations in the DNA from multiplying. However, if cell death does not occur, cells with these mutations have a higher likelihood of becoming cancerous. In addition, pathogenetic variants in the TRIM37 gene can impact the number and function of immune cells, leading to an increased risk of severe infections.

Mulibrey nanism is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

What are the treatments for mulibrey nanism syndrome (perheentupa sy...)?

Constrictive pericarditis may be treated with surgery (pericardiectomy) in symptomatic patients. Constriction-restriction assessments can be useful in determining the underlying cause of congestive heart failure and when to intervene. Diuretics may be prescribed for progressive heart failure. Difficulty breathing due to infection and/or exercise associated with abnormalities of the lungs can be treated with inhaled therapies and asthma medication. Hormone replacement therapy should be offered to children with growth hormone deficiency, delayed puberty, infrequent or very light menstrual periods, hypothyroidism, hypoadrenocorticism and abnormal ovaries or testes. Females with mulibrey nanism should be monitored closely for ovarian tumors, and all patients should be monitored for Wilms’ tumor. Patients who develop cancer can be treated with chemotherapy, surgery and multi-specialty care.

What are the risk factors for mulibrey nanism syndrome (perheentupa sy...)?

Mulibrey nanism syndrome (perheentupa syndrome) is an extremely rare genetic disorder with 110 reported cases worldwide. A characteristic feature of the disease is nanism, which means short stature. MULIBREY stands for Muscle, Liver, brain, and eye. The disease course onset is prenatal. After birth, the baby has problems feeding, breathing, and cardiac problems. The children also experience muscle weakness, hepatomegaly, widely-spaced eyes, fundi showing yellow dots and dispersed pigment, hypoplasia of the choroid, strabismus, and astigmatism.

Risk factors
1. It is caused by mutations in the gene TRIM37 on chromosome 17, which codes for a protein in the peroxisomes. The defect in the protein hampers the separation of genetic material during cell division, which leads to cell death to prevent chromosomal aberrations.
2. The mutations are recessive, which implies that the expression of the disease requires the mutant to be homozygous. Therefore, for the fetus to suffer from the disease, both parents must be either 3.
3. There is a 25% chance a baby born to carrier parents will be affected. And at conception, the second baby is 50% likely to be affected: while the first baby is born with the disease.

Symptoms
Infants often have characteristic abnormalities of the head and face, including a triangularly shaped face,Yellow discoloration deep within the eyes and other ocular abnormalities may be present but vision is usually normal
Conditions
Progressive growth failure
Drugs
Surgery (pericardiectomy),Diuretics may be prescribed for progressive heart failure,inhaled therapies and asthma medication for abnormalities of the lungs

Is there a cure/medications for mulibrey nanism syndrome (perheentupa sy...)?

Mulibrey nanism syndrome (perheentupa syndrome) is a rare genetic disorder that presents with severe progressive growth delays and abnormalities in multiple organs. While MULIBREY is an acronym for muscles, liver, brain, and eyes, nanism means short stature. Developmental delays begin in fetal life. In addition, the condition affects the circulatory and respiratory systems, liver, and muscles. It is so rare that, to date, only 110 cases have been reported worldwide. The mutations in the gene TRIM37 on chromosome 17 lead to the condition. The gene codes for a protein involved in the separation of DNA during cell division.
Treatment
Treatment involves addressing individual organ-related problems under the attention of distinct specialists.
1. Overgrowth of the heart muscle, called pericarditis, leads to constriction of circulation. In symptomatic patients with constrictions, doctors perform pericardiectomy.
2. It may also cause progressive heart failure, which can be prevented with the help of diuretics.
3. Inhaled therapies and asthma medications are used for breathing difficulties due to abnormalities in the lungs and respiratory infections.
4. Doctors may suggest hormone replacement therapy for children with a growth hormone deficiency, delayed puberty, infrequent or very light menstrual periods, hypothyroidism, hypoadrenocorticism, and abnormal ovaries or testes.
5. Female patients are likely to develop an ovarian tumor, and, regardless of gender, patients may develop a wilms' tumor. Chemotherapy, surgery, and multi-specialty care are the available options for the cases.

Symptoms
Infants often have characteristic abnormalities of the head and face, including a triangularly shaped face,Yellow discoloration deep within the eyes and other ocular abnormalities may be present but vision is usually normal
Conditions
Progressive growth failure
Drugs
Surgery (pericardiectomy),Diuretics may be prescribed for progressive heart failure,inhaled therapies and asthma medication for abnormalities of the lungs

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