Advanced searches left 3/3
Search only database of 8 mil and more summaries

X-linked spinal muscular atrophy type 2

Summarized by PlexPage
Last Updated: 02 July 2021

* If you want to update the article please login/register

General | Latest Info

X-linked spinal muscular atrophy type 2

Other namesSpinal muscular atrophy with arthrogryposis
SpecialtyNeurology

Spinal Muscular Atrophy is a group of inherited disorders that cause progressive muscle degeneration and weakness. Spinal Muscular Atrophy is the second leading cause of neuromuscular disease. It is usually inherited as an autosomal recessive trait. There are several types of SMA called subtypes. Each of the subtypes is based on the severity of the disorder and the age at which symptoms begin. There are three types of SMA that affect children before the age of 1 year. There are two types of SMA, type IV and Finkel type, that occur in adulthood, usually after age 30. Symptoms of adult-onset Spinal Muscular Atrophy are usually mild to moderate and include muscle weakness, tremor and twitching. The prognosis for individuals with SMA varies depending on the type of SMA and degree of respiratory function. A patient's condition tends to deteriorate over time, depending on the severity of symptoms. Spinal Muscular Atrophy affects 1 in 6 000 to 1 in 10 000 people. Three types of SMA affect children before age one year. Type 0 is the most severe form of Spinal Muscular Atrophy and begins before birth. Usually, first symptom of type 0 is reduced movement of the fetus that is first seen between 30 and 36 weeks of pregnancy. After birth, these newborns have little movement and have difficulties with swallowing and breathing. Type I Spinal Muscular Atrophy is another severe form of SMA. Symptoms of type 1 may be present at birth or within the first few months of life. These infants usually have difficulty breathing and swallowing, and they are unable to sit without support. Children with type II SMA usually develop muscle weakness between the ages of 6 and 12 months. They cannot stand or walk without help. Type III SMA is a milder form of SMA than types 0, I or II. Symptoms appear between early childhood and early adulthood. Individuals with type III SMA are able to stand and walk without help. They usually lose their ability to stand and walk later in life. There are two other types of Spinal Muscular Atrophy, type IV and Finkel type that occur in adulthood, usually after age 30. Symptoms of adult-onset SMA are usually mild to moderate and include muscle weakness, tremor and twitching. To make diagnosis of SMA, symptoms need to be present. When symptoms are present, diagnosis can be made by genetic testing. Gene alterations in SMN1 and VAPB genes cause SMA. Having extra copies of SMN2 gene can modify the course of SMA. Genetic testing on blood or tissue samples is done to identify whether there is at least one copy of the SMN1 gene by looking for its special makeup. Mutations in SMN1 gene cause type 0, I, II, III, and IV. Some people who have SMA type II, III, or IV have three or more copies of the SMN2 gene. Having these extra copies can modify the course of SMA. The more copies of SMN2 gene a person has, less severe his or her symptoms. Are

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Types of SMA

Spinal Muscle Atrophy is a serious heritable disease characterized by loss of motor neurons. Motor neurons are nerve cells that control movement of voluntary muscles. As disease progresses, patients lose the ability to move, swallow, talk, and even breathe. The disease is caused by mutation in the SMN1 gene, which contains information necessary to make SMN protein that is essential for Survival of Motor neurons. The second gene called SMN2 can also produce SMN protein, but not in amounts necessary for motor Neuron health. SMA is divided into types based on age of disease onset and severity of its symptoms. Severity is thought to depend on the SMN2 gene copy number that patient has, although this is not the only determinant. There are also some rare cases of SMA that are caused by mutations in genes other than SMN1.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Main

X-link infantile spinal muscular atrophy is a rare congenital disorder characterized by multiple joint contractures. Hall et al. 2 distinguish three different types of X-link spinal muscular atrophy: 1 severe lethal Type, characterized by severe contractures, scoliosis, chest deformities, hypotonia, and death due to respiratory insufficiency within three months of birth; 2 moderately severe Type, characterized by severe contractures, ptosis, microphallus, cryptorchidism, inguinal hernias, and normal intelligence; and 3 resolving Type, characterize by mild to moderate contractures at birth that improve with time. Progressive loss of anterior horn cells was cited as the cause of severe lethal form of X-link spinal muscular atrophy. Greenberg et al. 3 describe under label X-link infantile spinal muscular atrophy similar disorder to X-link spinal muscular atrophy Type I 2 that appears to be X-link recessive and was associated with hypotonia, areflexia, chest deformities, facial dysmorphic features, and congenital joint contractures arthrogryposis. Findings of electromyography and muscle biopsy were consistent with autosomal recessive infantile spinal muscular atrophy werdnig-Hoffmann, MIM 253300. We have previously described meiotic breakpoint mapping concordance analysis, and whole chromosome multipoint linkage analysis to X-link spinal muscular atrophy family report by Greenberg et al. 3 We show localization of disease gene to pericentromeric interval from Xpll. 3-qll. 2 z max = 2. 63; between MAOB and marker DXS991 1. In this report, we extend our previous clinical and molecular investigations to eight new unrelated families with disease presentation and inheritance similar to that described by Greenberg et al.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Signs & Symptoms

Following resources from Cure SMA provide description of symptoms, as well as videos to assist with early diagnosis: SMA type 0 is the most severe form of disease and is characterized by decreased fetal movement, joint abnormalities, difficulty swallowing and respiratory failure. SMA type 1 is the most common type of SMA and is also a severe form of the disease. Infants with SMA type 1 experience severe weakness before 6 months of age and never sit independently. Muscle weakness, lack of motor development and poor muscle tone are major clinical manifestations of SMA type I. Infants with gravest prognosis have problems sucking or swallowing. Some show abdominal breathing in the first few months of life. Muscle weakness occurs on both sides of the body and ocular muscles are not affect. Twitching of tongue is often see. Intelligence is normal. Most affected children die before two years of age but survival may be dependent on degree of respiratory function. For more information about SMA type 1, choose Werdnig Hoffman Disease as your search term in Rare Disease Database. The onset of weakness in SMA type 2 patients is usually between 6 and 12 months. Affected children are able to sit independently early in development but are unable to walk even 10 feet independently. Trembling of fingers is almost always seen in SMA type 2. Approximately 70 % of those affected do not have deep tendon reflexes. Those affected with SMA type 2 are usually not able to sit independently by mid-teens or later. Patients with SMA type 3 learn to walk but fall frequently and have trouble walking up and down stairs at 2-3 years of age. Legs are more severely affected than arms. Long-term prognosis depends on the degree of motor function attained as child. For more information about SMA3 choose Kugelberg Welander syndrome as your search term in Rare Disease Database. The Onset of muscle weakness for those with SMA type 4 is after age 10 years; these patients usually are ambulatory until age 60 years. Complications of SMA include scoliosis, joint contractures, pneumonia and metabolic abnormalities such as severe metabolic acidosis and dicarboxylic aciduria.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Causes

Spinal muscular atrophy is a genetic disorder characterized by weakness and wasting in muscles used for movement. It is caused by loss of specialized nerve cells, called motor neurons that control muscle movement. Weakness tends to be more severe in muscles that are close to the center of the body compared to muscles away from the body's center. Muscle weakness usually worsens with age. There are many types of spinal muscular atrophy that are caused by changes in same genes. Types differ in age of onset and severity of muscle weakness; however, there is overlap between types. Other forms of spinal muscular atrophy and related motor neuron diseases, such as spinal muscular atrophy with progressive myoclonic epilepsy, spinal muscular atrophy with lower extremity predominance, X-link infantile spinal muscular atrophy, and spinal muscular atrophy with respiratory distress type 1 are caused by mutations in other genes. Spinal muscular atrophy type 0 is evident before birth and is the rarest and most severe form of the condition. Affected infants move less in the womb, and as a result, they are often born with joint deformities. They have extremely weak muscle tone at birth. Their respiratory muscles are very weak and they often do not survive past infancy due to respiratory failure. Some infants with spinal muscular atrophy type 0 also have heart defects that are present from birth. Spinal muscular atrophy type I is the most common form of the condition. It is a severe form of disorder with muscle weakness evident at birth or within the first few months of life. Most affected children cannot control their head movements or sit unassisted. Children with this type may have swallowing problems that can lead to difficulty feeding and poor growth. They can also have breathing problems due to weakness of respiratory muscles and an abnormally bell-shape chest that prevents lungs from fully expanding. Most children with spinal muscular atrophy type I do not survive past early childhood due to respiratory failure. Spinal muscular atrophy type II is characterized by muscle weakness that develops in children between the ages of 6 and 12 months. Children with this type can sit without support, although they may need help getting to seat position. However, as muscle weakness worsens later in childhood, affected individuals may need support to sit. Individuals with spinal muscular atrophy type II cannot stand or walk unaided. They often have involuntary trembling in their fingers, spine that curve side-to-side, and respiratory muscle weakness that can be life-threatening. The life span of individuals with spinal muscular atrophy type II varies, but many people with this condition live into their twenties or thirties. Spinal muscular atrophy type III typically causes muscle weakness after early childhood. Individuals with this condition can stand and walk unaided, but over time, walking and climbing stairs may become increasingly difficult. Many affected individuals require wheelchair assistance later in life. People with spinal muscular atrophy type III typically have normal life expectancy.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Related Disorders

SMA is a Genetic Disease, meaning that it runs in families, and it is passed from parents to their children through their genes. In our body we have millions of cells, each of them containing a nucleus. It is in the cell nucleus that chromosomes are locate. These are made of proteins and DNA molecules, which contain biological instructions that make each species and each person unique. Molecule structure keep DNA tightly pack. DNA is a very long molecule and is packaged as chromosomes. Each of US has 46 chromosomes arranged into 23 pairs, one inherited from the mother and the other from the father. Twenty-two chromosomal pairs are know as autosomes because they are found in both genders. 23 pair is sex chromosome and determines your gender. The main function of chromosomes is to ensure that DNA is accurately copied and distributed during cell division. However, mistakes occur on rare occasions. In autosomal disorder such as SMA, mutation occurs in one of 22 non-sex chromosomes. As a result, disease may affect both males and females. SMA is also a recessive condition, meaning that people who carry one mutate gene and one healthy gene will not have the condition, but will be carriers who may pass disease onto their children. When two people carrying mutation in their SMN1 gene have a child together, their child has a risk of carrying two faulty copies of the gene. The child will then have Spinal Muscular Atrophy. The risk stays the same for each pregnancy. Here are some examples of inheriting SMA: 25 percent chance of having child without SMA 25 percent chance of having child with SMA 50 percent chance of having carrier child without SMA 50 percent chance of having child without SMA 50 percent chance of having carrier child without SMA one parent has SMA, other doesnt and isnt carrier: 100 percent of having carrier child without SMA one parent has SMA and other is carrier: 50 percent chance of having child with SMA 50 percent chance of having carrier child without SMA 100 percent chance of having child with SMA

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Diagnosis

The outlook for patients with SMA type 2 depends on age of diagnosis, and early care and support they receive, especially with respiration. While some people with SMA type 2 succumb to disease at an early age, many survive into adulthood. SMA News Today is strictly news and information website about disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek advice of your physician or other qualified health provider with any questions you may have regarding medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Standard Therapies

There is currently no cure for SMA. However, treatments can help to manage symptoms of disease. Parents of children with SMA type 2 will need to meet with a Multidisciplinary Health Care team to ensure that their child is receiving needed care. This will include a physiotherapis t or an occupational therapist who can help parents support their child in learning to move and speak. PhysiotherapistA can design individualized exercise Program, while occupational therapists can prescribe aids and adaptations such as braces or wheelchairs to maximize mobility. Spinal Muscular Atrophy is a rare Genetic condition that causes progressive weakness and wasting of muscles. It is a spectrum of conditions most commonly caused by a gene defect on chromosome 5q called survival Motor neuron Gene 1, referred to as SMN1. With this gene being faulty, individual is unable to produce enough of important protein, called SMN, to have healthy nerves. This results in a reduction in signalling from the brain to muscles, leading to lack of movement which over time leads to wasting. It can affect muscles involved in movement, breathing, speaking and swallowing. Due to the existence of many types of SMA, each individual is affected differently, and will require different management and support. SMA does not affect intelligence or personality and is not learning difficulty. Movement difficulties eg difficulty walking, sitting-up, carrying objects Problems with breathing Problems with swallowing common signs include: Muscle weakness Muscle wasting low Muscle tone Muscle twitches, loss of Muscle reflexes. The main types of SMA are called types 1, 2, 3 and 4. These are all associated with defective SMN1 Gene. There are a number of other SMAs that are not associated with this Gene. Below table outline four main types of Spinal Muscular Atrophy: there are some, even rarer, types of SMA that do not involve SMN1 Gene. A few examples of these are: x-link Spinal Muscular Atrophy. This is characterise by severe muscle weakness and breathing difficulty, and affect Children often have misshapen bones. Spinal Muscular Atrophy with respiratory distress. SMARD is usually diagnosed in the first year of life and causes severe respiratory problems. Spinobulbar Muscular Atrophy or Kennedys disease. SBMA predominantly affects men. It usually starts in middle age and does not affect life expectancy. Distal Spinal Muscular Atrophy. DSMA is a type of SMA that mainly affects lower parts of arms and legs, such as hands and feet. More information on rarer types of SMA can be found on the SMA UK website. The most direct way to test for SMA is with a Genetic blood test to confirm faulty gene. As well as blood tests, there is sometimes a need for further investigations of nerve and muscle function. This can include: specific blood tests for other Neuromuscular conditions, Muscle biopsy. This is where a needle is used to take small samples of muscle tissue is removed for analysis.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Inheritance

SMA is characterized by loss of motor neurons, nerve cells in the Spinal cord. It is classified as motor neuron Disease. The most common form of SMA is caused by a defect in the SMN1 gene on chromosome 5. In 94 % of all SMA cases, this mutation involves deletion in a segment known as exon 7. This area is located in the long arm of chromosome 5, in 5q13. 2 region. Mutations in the SMN1 gene lead to deficiency of motor neuron protein called SMN, which stands for survival of motor neuron. As its name implies, this protein is responsible for gene expression necessary for normal motor neuron function. More rarely, mutation in the X-chromosome gene called UBE1 causes X-link SMA. The UBE1 gene carries instructions for ubiquitin-activating enzyme 1, which normally helps attach molecular tag to proteins to mark them for destruction. Flaws in cytoplasmic dynein 1 heavy chain 1 gene on chromosome 14 have been found to lead to another rare form of SMA called SMA-lead. Normally, SMN1 genes produce full-length and fully functional SMN protein. But when SMN1 gene has mutations, as in the chromosome 5-related form of SMA, insufficient levels of SMN protein are produce. A neighboring gene on chromosome 5, called SMN2, also produces SMN protein. Most of the protein made from instructions carried by SMN2 genes is not functional, but a small percentage, around 10 to 15 % is functional. People can have multiple copies of the SMN2 gene. Normally, number varies between zero and eight copies. In the chromosome 5-related form of SMA, more SMN2 gene copies a person has, more functional SMN protein is available. As a result, milder disease course is likely to be. Having three or more copies of SMN2 gene is associated with less severe disease manifestation. Genetic testing can tell how many SMN2 genes a person has and roughly predict the course of SMA that is likely to result. SMA severity also may depend on disease modifiers, which don't cause disease but can affect onset and severity by influencing various biological pathways. Levels of both plastin 3 protein and ZPR1 protein have been identified as modifiers of SMN-relate SMA and could become therapeutic targets. In addition, testing for these protein levels could help predict disease severity, and insight into the activities of these proteins could shed new light on disease processes. Genetic information moves from its storage form as DNA to a set of instructions know as RNA, from which protein molecules are make. Most of RNA instructions from SMN1 gene tell cell to make full-length SMN protein. Most of the instructions from SMN2 gene tell cells to make short SMN protein. Chromosome 5-relate SMA follows an inheritance pattern know as autosomal recessive. Diseases that are recessive require two gene flaws, usually one from each parent, but occasionally one from one parent and one that occurs as the fetus is being form.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Prognosis

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms list. This information comes from a database called Human Phenotype Ontology. HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use HPO ID to access more in-depth information about symptom. Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-center information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors / clinics. Visit groups ' websites or contact them to learn about services they offer. Inclusion on this list is not endorsement by GARD.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Spinal Muscular Atrophy

Most common types of SMA are associated with mutation in the SMN1 gene, which is located on chromosome 5. About 95 percent of people with SMA have mutations where a section of SMN1 gene is deleted in both copies of the gene. The SMN1 gene provides instructions for making Survival Motor Neuron protein that is found in all parts of the body, and exists at high levels in the spinal cord. This protein is important for maintaining the function of motor Neuron cells. As result of mutations in SMN1 gene, little or no SMN protein is make. Research findings indicate that motor neurons are particularly vulnerable to shortage of SMN protein and die prematurely. In humans, there is a second gene called SMN2. Some people have three or more copies of SMN2 gene. Like the SMN1 gene, SMN2 genes provide instructions for making SMN protein. Extra SMN2 genes can help provide some of the SMN protein. But fewer full-size SMN proteins are produced from SMN2 genes compared to SMN1 gene. In these people, SMA symptoms are much less severe. Finkel Type SMA is associated with mutations in VAPB gene located on chromosome 20. This gene contains instructions to produce VAPB protein that is associated with membrane that surround endoplasmatic reticulum, which is where newly-make proteins acquire their three-dimentional structure and are prepared to be transported within cell or to cell surface. The mutation causes amino acid proline to be replaced with amino acid serine at position 56. This causes amyothrophic lateral sclerosis in some people and SMA in others. Mutate proteins cannot activate unfolded protein response, resulting in protein aggregates that lead to cell death. Motor neurons are particularly vulnerable to cell death, caused by protein aggregates. The DYNC1H1 gene-locate on chromosome 14-provide instructions to make protein that is part of a complex group of proteins, know as dynein, which are found in cytoplasm. In neurons, dynein moves proteins and other cellular materials away from junctions between neurons to the center of the cell, facilitating passage of chemical messages from one Neuron to another. Mutations in DYNC1H1 gene cause form of SMA called SMA-lead, which primarily affect legs. As a result, movement of proteins and cellular materials is impaired, resulting in a decrease in chemical messaging between neurons that control muscle movement. Mutations in UBA1 gene cause X-link infantile SMA condition. This gene, located on the X chromosome, is responsible for making an ubiquitin-activating enzyme called E1 involved in degradation of proteins within cells. Protein degradation is essential to remove damage or unnecessary proteins and to maintain normal function of cells. At least three mutations in the UBA1 gene have been find. Two of them are thought to lead to enzyme with impaired function.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

logo

Plex.page is an Online Knowledge, where all the summaries are written by a machine. We aim to collect all the knowledge the World Wide Web has to offer.

Partners:
Nvidia inception logo

© All rights reserved
2021 made by Algoritmi Vision Inc.

If you believe that any of the summaries on our website lead to misinformation, don't hesitate to contact us. We will immediately review it and remove the summaries if necessary.

If your domain is listed as one of the sources on any summary, you can consider participating in the "Online Knowledge" program, if you want to proceed, please follow these instructions to apply.
However, if you still want us to remove all links leading to your domain from Plex.page and never use your website as a source, please follow these instructions.