Who Else Wants To Know About Marfan Syndrome?

Who Else Wants To Know About Marfan Syndrome?

Marfan syndrome (MFS) is in particular, a connective tissue genetic disorder. In this case, Individuals with Marfan syndrome tend to be tall and slim, with long arms, legs, fingers and toes. Moreover, usually, they have flexible joints and scoliosis, too. Likewise, the most serious complications involve the heart and aorta, with an increased risk of mitral valve prolapse and aortic aneurysm. Additionally, other commonly affected areas include the lungs, eyes, bones and the covering of the spinal cord.it is an autosomal dominant disorder. The disorder is inherited from a parent about 75% of the time, although it is a new mutation of 25% of the time. So, it includes a mutation to the gene that creates fibrillin, leading to irregular connective tissue.

SIGNS & SYMPTOMS OF MARFAN SYNDROME

SKELETAL SYSTEM

With this in mind, much of the easily recognizable symptoms apply to the skeletal system. So, many individuals with Marfan’s syndrome grow to above-average height, and some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes. 

EYES

Ectopia lentis, Lens dislocation, other signs and symptoms affecting the eye include increased length along an axis of the globe, myopia, corneal flatness, strabismus, exotropia, and esotropia.

CARDIOVASCULAR SYSTEM

Undoubtedly, the most serious signs and symptoms associated with Marfan’s syndrome involve the cardiovascular system: undue fatigue, shortness of breath, heart palpitations, racing heartbeats, or chest pain radiating to the back, shoulder, or arm. Because of inadequate circulation, the cold arms, hands, and feet are connected to MFS. Further examination can suggest a heart murmur, irregular reading on an ECG, or angina symptoms. Because underlying connective tissue abnormalities cause MFS, the incidence of dehiscence of the prosthetic mitral valve is increased.

LUNGS

Pulmonary symptoms are not a major feature of MFS. Spontaneous pneumothorax is common. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis, and, if not treated, death. Other possible pulmonary manifestations of MFS include sleep apnea and idiopathic obstructive lung disease. Cystic changes, emphysema, pneumonia, bronchiectasis, bullae, apical fibrosis and congenital malformations such as hypoplasia of the middle lobe have been identified as pathological changes in the lungs.

NERVOUS SYSTEM

Dural ectasia, a weakening of the dural sac’s connective tissue enclosing the spinal cord, can lead to a loss of quality of life. It can be present for a long time, with no visible symptoms. Symptoms that can arise include lower back pain, pain in the hands, stomach pain, other lower extremity neurological symptoms, or headaches-symptoms that generally worsen while lying flat. Other spinal issues associated with MFS include degenerative disc disease, spinal cysts, and dysfunction of the autonomic nervous system.

CONCLUSION

So, Marfan’s syndrome (MFS) is a genetic disorder of the connective tissue. In particular, individuals with Marfan syndrome tend to be tall and slim, with long arms, legs, fingers and toes. In particular, usually, they have flexible joints and scoliosis, too. The most serious complications involve the heart and aorta, with an increased risk of mitral valve prolapse and aortic aneurysm. Lungs, eyes, bones and the covering of the spinal cord. It is an autosomal dominant disorder. The condition is inherited from a parent 75% of the time, it is a new mutation 25% of the time. So, it involves a mutation to the gene that makes fibrillin, which results in abnormal connective tissue.

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Five major Clinical Manifestations of Marfan’s Syndrome

Marfan’s Syndrome (MFS) is a connective tissue genetic disorder. Individuals with Marfan syndrome tend to be tall and thin, with long arms, legs, fingers and toes. Usually, they may have unstable joints and scoliosis. The most severe risks include the heart and aorta, with an elevated risk of prolapse of the mitral valve and aortic aneurysm. Other frequently affected areas include the lungs, skin, bones and spinal cord. its presence is an autosomal dominant condition. Approximately 75% of the time, the disorder is inherited from a parent, while 25% of the time it is a new mutation. It includes a gene mutation that produces fibrillin, resulting in irregular connective tissue.

Signs and Symptoms

Skeletal System

Much of the readily recognizable symptoms apply to the skeletal system. Many people with Marfan’s syndrome grow to a higher than average height, and some have unusually long, slender limbs with thin, frail wrists and long fingers and toes.

Eyes

Ectopia lentis, Lens dislocation, other signs and symptoms affecting the eye include increased length along an axis of the globe, myopia, corneal flatness, strabismus, exotropia, and esotropia.

Cardiovascular system

The cardiovascular system involves the most serious signs and symptoms associated with Marfan’s syndrome: undue fatigue, shortness of breath, heart palpitations, heartbeats racing, or back, shoulder, or arm chest pain. Because of inadequate circulation, the cold arms, hands, and feet can also be connected to MFS. Further examination can suggest a heart murmur,
irregular reading on an ECG, or angina symptoms. Since underlying connective tissue malfunctions cause MFS, the occurrence of prosthetic mitral valve dehiscence is increased.

Lungs

Pulmonary symptoms are not a significant feature of MFS but it is normal to have a spontaneous pneumothorax. Air escapes from a lung in spontaneous unilateral pneumothorax and occupies the pleural space between the chest wall and a lung. Partially the lung is squeezed or collapsed. That can lead to pain, shortness of breath, cyanosis, and death if not treated.
Other possible pulmonary manifestations of MFS include idiopathic obstructive lung disease and sleep apnea. Pathological changes in the lungs, such as cystic changes, emphysema, pneumonia, bronchiectasis, bullae, apical fibrosis and congenital malformations such as hypoplasia of the middle lobe were identified.

Nervous system

Dural ectasia, a deterioration of the dural sac’s connective tissue enclosing the spinal cord may lead to a loss of quality of life. It can be present for a long time, with no noticeable symptoms. Symptoms that may occur are lower back pain, pain in the legs, abdominal pain, other lower extremity neurological symptoms, or headaches-symptoms that usually diminish when lying flat. Many spinal disorders related to MFS include degenerative disc disease, spinal cysts and autonomic nervous system dysfunction.

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The clinical manifestations of Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is an indolent, progressive development of lung-wide smooth muscle cells, pulmonary blood vessels, lymph, and pleurae. It is uncommon and only occurs in young people.

CAUSES

The condition typically develops naturally but LAM bears many parallels to tuberous sclerosis (TS) pulmonary findings. Mutations in the complex-2 gene (TSC-2) of tuberous sclerosis have been identified in LAM cells and angiomyolipomas that occur in up to 50% of LAM patients. Those observations indicate 1 out of 2 options:

  • Somatic mosaicism for TSC-2 mutations within the lungs and kidneys results in foci of disease superimposed against a background of normal cells within these tissues.
  • LAM represents a low-grade, destructive, metastasizing neoplasm, perhaps of uterine origin, that spreads through the lymphatic system.

PATHOPHYSIOLOGY

The proliferation of cells with lymphangioleiomyomatosis (LAM) can obstruct bronchioles, leading to obstruction of the airflow, air trapping, bullae formation, and pneumothoraces. The lymphatic blockage may lead to lymphangioleiomyomas, chylothorax, and chylous ascites. Excessive proteolytic activity involving an imbalance of the elastase / alpha1-antitrypsin system or metalloprotease (MMPs) system and its inhibitors may be important in the degradation and development of cysts in the lung.

CLINICAL MANIFESTATIONS

  • Dyspnea
  • Cough
  • Chest Pain
  • Hemoptysis
  • Pneumothorax

DIAGNOSIS

  • Chest X-Ray
  • VEGF – D Testing
  • Lung Biopsy

TREATMENT

NON-PHARMACOLOGICAL TREATMENT

  • Oxygen therapy
  • Pulmonary Rehabilitation
  • Removal of air or fluid around the lungs or abdomen to help you breathe better
  • Surveillance and treatment of osteoporosis
  • Standard vaccinations to prevent respiratory infections
  • Bronchodilators to help open airways and improve breathing

PHARMACOLOGICAL TREATMENT

  • Sirolimus (rapamycin). The only medication that may be helpful in treating LAM is sirolimus. This medication may help to improve lung function, reduce symptoms, and shrink kidney tumours.
  • Hormones. Because LAM occurs only in younger women and tends to get worse during pregnancy, some physicians recommend treatment to reduce the effects of estrogens.

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Holt-Oram Syndrome: A rare genetic condition

Holt-Oram syndrome, also called a right-hand syndrome, is a genetic condition characterized by upper limb and heart defects. This is also known as an atrio-digital syndrome, atriodigital dysplasia, heart-limbing syndrome, ventriculo-radial syndrome. It is an autosomal dominant condition, which affects the arms and hands of the bones and also causes heart attacks.

CAUSES

Holt-Oram syndrome is an autosomal dominant genetic disorder that can be inherited. The TBX5 gene currently contains more than 70 known mutations that cause Holt-Oram syndrome. Potential triggers for the majority of the individuals affected include inadequate reading and translation of the TBX5 gene during protein development.

PATHOPHYSIOLOGY

UPPER LIMB INVOLVEMENT

Abnormalities may be asymmetric or unilateral and may include longitudinal, carpal, and thenar bones. Such bones are affected by aplasia, hypoplasia, fusion, or anomalous development with a variety with phenotypes, including triphalangeal or missing thumbs. Malformations or carpal bone fusions are the most prevalent findings in individuals with Holt-Oram syndrome. The only findings found in all affected individuals are carpal bone anomalies.

CARDIAC INVOLVEMENT

Around 75% of patients have any heart abnormality. The abnormality in most patients is either an atrial septal defect (ASD), or a ventricular septal defect (VSD), varying in number, scale, and location. Cardiac abnormalities can also include defects in cardiac conduction such as progressive atrioventricular blockage and atrial fibrillation.

SIGNS AND SYMPTOMS

UPPER LIMB DEFORMITY INCLUDES THE FOLLOWING FEATURES:

  • Always present but may be unilateral or bilateral
  • Left-sided abnormalities often more severe than a right arm or hand abnormalities
  • Unequal arm lengths due to aplasia, hypoplasia, fusion, or anomalous development of the radial, carpal, and thenar bones
  • Abnormal forearm pronation and supination
  • Triphalangeal or absent thumbs
  • Possible abnormal opposition of the thumb
  • Possible sloping shoulders and restriction of shoulder joint movement
  • Phocomelia

CARDIAC INVOLVEMENT INCLUDES THE FOLLOWING SIGNS:

  • Bradycardia
  • Irregular pulse (ectopy)
  • Irregular pulse that occurs irregularly (atrial fibrillation)
  • Wide, fixed splitting of the second heart sound
  • Pulmonary systolic flow murmur
  • Holosystolic murmur

TREATMENT

No drugs are effective in treating patients with Holt-Oram syndrome with anatomical deficiencies. It can be used to prophylaxis antibiotics. Patients with pulmonary hypertension should be found to be anticoagulant. Patients with atrial fibrillation should suggest cardioversion, antiarrhythmic drug treatment, or anticoagulation.

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Understanding The Background Of Pemphigus Erythematosus

Pemphigus erythematosus, also known as Senear-Usher syndrome, is a condition with association with lupus erythematosus (LE) and pemphigus foliaceus characteristics. Pemphigus is shown in interkeratinocyte material by the deposits of acantholysis and immunoglobulin. It is proposed that high doses of UV light are the source of the desmoglein-1 ectodomain cleavage. As in the case of pemphigus foliaceus the circulating anti-desmoglein-1 antibodies precipitate this cleaved off ectodomain along with the membrane zone of the basement, resulting in a lupus band-like look. The lupus portion of pemphigus erythematosus is shown by circulating antinuclear antibodies (ANA) and often by immunoglobulin and by complementing deposits at the dermo-epidermal junction

CAUSES

Patients suffering from pemphigus develop an allergic reaction to desmosomes. The main antigen is desmoglein 1 in patients with pemphigus foliaceus and its variant, pemphigus erythematosus Desmogleins are essential desmosomal proteins for adhesion to keratinocytes. The binding of autoantibodies is postulated to lead to a cascade of intracellular biochemical events that result in the loss of desmosome function.

PATHOPHYSIOLOGY

Patients with pemphigus erythematosus have vesiculobullous or superficially eroded lesions that may ooze and crust, particularly in areas exposed to the sun, such as the face, upper chest and back.

SIGNS AND SYMPTOMS

  • Blisters
  • Rash
  • Itching sensation

COMPLICATIONS

  • Infection of your skin
  • Sepsis
  • Malnutrition

TREATMENT

  • Tetracycline
  • Niacinamide
  • Cyclophosphamide
  • Methotrexate
  • Parenteral gold
  • Hydroxychloroquine
  • Plasmapheresis
  • Mycophenolate mofetil
  • Extracorporeal photochemotherapy
  • Rituximab
  • Dexamethasone-cyclophosphamide combination

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Krabbe Disease: Causes, Pathophysiology, Symptoms and Complications

Krabbe disease is a rare nervous-system genetic disorder. It is a form of brain disease which is known as leukodystrophy. It is also known as leukodystrophy of globoid cells, or lipidosis of galactosylceramides.

CAUSES

Krabbe disease is caused by a mutation in the gene GALC. People with this gene deficiency will not make enough of the substance called beta-galactosidase (galactosylceramidase) galactocerebroside. The enzyme is required by the body to create myelin. Myelin surrounds and protects nerve fibres. Without this enzyme, myelin breaks down, brain cells die, and nerves inside the brain and other parts of the body do not function properly. Krabbe disease is inherited and is a recessive autosomal disorder. Krabbe disease can grow at different ages: In the first months of life, the early-onset disease appears. The majority of children with this type of illness die before they reach 2 years of age. Late-onset Krabbe disease starts in late infancy or early teenage years.

PATHOPHYSIOLOGY

Galactosylceramide is biosynthesized by ceramide galactosylation. It is highly concentrated in the sheath of myelin, where it is synthesized in oligodendroglia and cells like Schwann. The addition of a group of sulfates will convert galactosylceramide to sulfatide.

The composition of myelin in Krabbe disease isn’t qualitatively abnormal. The accumulation causes globoid cells to grow. Psychosine also accumulates and is thought to be a highly cytotoxic substance responsible for the widespread destruction of oligodendroglia which produces myelin. The rapid degradation of oligodendroglia leads to a breakdown of myelin, and further reduction of myelin production, causing the following symptoms.

SIGNS AND SYMPTOMS

  • Changing muscle tone from floppy to rigid
  • Hearing loss that leads to deafness
  • Failure to thrive
  • Feeding difficulties
  • Irritability and sensitivity to loud sounds
  • Severe seizures
  • Unexplained fevers
  • Vision loss that leads to blindness
  • Vomiting

COMPLICATIONS

  • Blindness
  • Deafness
  • Severe problems with muscle tone

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