Question 1 of 10

    Ataxia Telangiectasia (Ataxia-telangiectasia)

    Ataxia telangiectasia (AT) is a rare neurodegenerative disorder inherited through an autosomal recessive pattern, mainly characterized by a progressive neurologic impairment together with cerebellar ataxia.

    The disorder is related to the following process: hereditary.

    Presentation

    The severity of AT varies between the subjects. Ataxia is undoubtedly one of the most important sings, and among the first ones to appear between 3 and 5 years of age. This is soon followed by oculomotor apraxia, the difficulty in moving head and eye, together with frequent involuntary movements. These later result in more pronounced complications like difficulty in reading, writing, speaking or standing still, that soon end up including difficulty in eating and swallowing (dysphagia). As previously said, telangiectasia tends to appear later in life, between 5 and 8 years of age, especially on the sclera of the eye, making subjects appear bloodshot. This sign never results in bleeding or itching, and never changes or disappears in relation to time, weather or emotions.

    After this first stage the immune-related signs and complications begin to appear, like infections and increased cancer risk. Infections are the result of very low levels of lymphocytes (especially T-cells), and mainly tend to affect the respiratory track. Cancer, instead, tends to manifest itself in the form of lymphomas and leukemia, even though other forms of tumor might occur [17]. AT can also cause many complications in the skin, which mainly involve signs of early aging, vitiligo or chronic inflammatory skin diseases [18].

    Skin
    Cutaneous Manifestation
    • Kieslich M, Schubert R, Zielen S, Voss S Orphanet J Rare Dis 2015 Dec 9;10:155 PMID 26645295 Non-homologous end joining: emerging themes and unanswered questions Radhakrishnan SK, Jette N, Lees-Miller SP DNA Repair (Amst) 2014 May;17:2-8 PMID 24582502 Cutaneous[atlasgeneticsoncology.org]
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  • Eyes
    Strabismus
    • Strabismus and nystagmus may also be present.[aao.org]
    • Eye misalignments ( strabismus ) are common, but may be treatable.[en.wikipedia.org]
    • Impairment of the extrapyramidal movement system is common in A-T, as are oculomotor abnormalities such as apraxia, strabismus and nystagmus.[atlasgeneticsoncology.org]
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  • respiratoric
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  • neurologic
    Ataxia
    • Friedreich ataxia (FA) is the most common genetic cause of ataxia in children.[en.wikipedia.org]
    • Learn About Ataxia Posted on October 30, 2017 2017 Research Drive It’s time for the Annual Ataxia Research Drive![ataxia.org]
    • Friedreich's ataxia Friedreich's ataxia is the most common type of hereditary ataxia (caused by genes you've inherited).[nhs.uk]
    Cerebellar Ataxia
    • ataxia G11.2 Late-onset cerebellar ataxia G11.3 Cerebellar ataxia with defective DNA repair G11.4 Hereditary spastic paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia, unspecified G12 Spinal muscular atrophy and related syndromes G12.0[icd10data.com]
    • Home / Education / Ataxia Telangiectasia Definitive Male or female patient with either increased radiation induced chromosomal breakage in cultured cells, or progressive cerebellar ataxia, who has disabling mutations on both alleles of ATM.[esid.org]
    • Absence of mutations in ATM, the gene responsible for ataxia telangiectasia in patients with cerebellar ataxia.[appliedradiology.com]
    • Ataxia Telangiectasia [ATM]: Autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy.[jewishgeneticdiseases.org]
    • Name ataxia-telangiectasia FlyBase ID FBhh0000167 Disease Ontology Term Parent Disease OMIM Parent Disease Ontology Term This report describes ataxia-telangiectasia (AT), which is a subtype of autosomal recessive cerebellar ataxia.[flybase.org]
    Slurred Speech
    • Ataxia Telangiectasia (AT), which is another autosomal recessive cerebellar ataxia incidence of 1:40,000–1:100,000 worldwide characterized by the onset of truncal ataxia at the time of walking ataxic syndrome is progressive and involves slurred speech[gpnotebook.co.uk]
    • The first signs are usually lack of balance, slurred speech, and lack of muscles control.[pediatriconcall.com]
    • Symptoms: Progressive difficulty controlling body movements (ataxia) particularly while walking, slurred speech, inability to follow an object with one’s eyes, dilated blood vessels and spiderlike veins around the corners of the eyes and on the ears and[jewishgeneticdiseases.org]
    • Their motor skills will develop slower than normal and they will have poor balance and slurred speech.[counsyl.com]
    • Clinical Features Ataxia Telangiectasia (A-T) is characterized by early onset (1-4 years) progressive cerebellar ataxia, telangiectasias of the conjunctivae, oculomotor apraxia, choreoathetosis, immunodeficiency, slurred speech, frequent infections, and[preventiongenetics.com]
    Dysarthria
    • Signs and symptoms of Friedreich's ataxia can include: problems with balance and co-ordination, often causing wobbliness, clumsiness and frequent falls increasingly slurred, slow and unclear speech (dysarthria) increasing weakness in the legs – many people[nhs.uk]
    • Symptoms are characterized by progressive cerebellar ataxia, dysarthria, oculomotor apraxia, chorea/dystonia, oculocutaneous telangiectasias, endocrine dysfunction, immunodeficiency, premature aging, radiosensitivity, and predisposition to cancer.[scielo.br]
    • These features include ataxia of the trunk and limbs, progressive supranuclear ophthalmoplegia, dysarthria, swallowing incoordination, facial hypomimia and delayed peripheral neuropathy.[erydel.com]
    • Truncal ataxia is usually noted during the second year of life, with subsequent development of dysarthria, dystonia, and choreoathetosis.[aao.org]
    • Ataxia is often accompanied by difficulty speaking ( dysarthria ), drooling; and an impaired ability to coordinate certain eye movements (oculomotor apraxia ), including the occurrence of involuntary, rapid, rhythmic motions (oscillations) of the eyes[webmd.com]
    Nystagmus
    • […] of skin areas exposed to sunlight Discoloration of skin (coffee-with-milk-colored spots) Enlarged blood vessels in skin of nose, ears, and inside of the elbow and knee Enlarged blood vessels in the whites of the eyes Jerky or abnormal eye movements ( nystagmus[medlineplus.gov]
    • Strabismus and nystagmus may also be present.[aao.org]
    • During an episode, someone with episodic ataxia may experience: problems with balance and co-ordination slurred, slow and unclear speech (dysarthria) muscle spasms involuntary eye movements (nystagmus) vertigo , migraines and tinnitus Episodic ataxia[nhs.uk]
    Poor Coordination
    • These two key features compose the general significance or meaning of what this condition is Children with Ataxia-Telangiectasia have poor coordination of movements, problems in maintaining posture, speech difficulties, and spider-like veins on the skin[dovemed.com]
    • coordination and balance (cerebellar ataxia ), red eyes due to widening of small blood vessels in the conjunctiva ( ocular telangiectasia), and recurrent sinus and lung infections.[medicinenet.com]
    • The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements.[flybase.org]
    • The most important symptoms are as follows: Neurologic abnormalities resulting in poor coordination and an unsteady gait (ataxia).[healthofchildren.com]
    • The most common symptoms of A-T include: poor coordination (ataxia) and stiff or jerky movements difficulty in coordinating eye and head movements (oculomotor apraxia) small dilated blood vessels (telangiectasia) on the whites of the eyes frequent coughs[attest-trial.com]
    Neurologic Manifestation
    • This is the first large-scale clinical trial of any drug to treat the neurologic manifestations of AT.[innogest.it]
    • Treatment Treatment Options: No treatment is known for the neurologic manifestations.[disorders.eyes.arizona.edu]
    • Abnormal neurogenesis is another contributor to the neurological manifestation of the disease.[dovepress.com]
    • Ataxia-telangiectasia was not described as a distinct clinical entity for another 16 years until Boder and Sedgwick [ 5 ] in 1957 and Biemond [6] in 1957, with the aid of autopsies, reported organ developmental abnormalities; neurologic manifestations[emedicine.medscape.com]
    • Optimal management of these other changes – many of which are amenable to treatment – may help minimize the neurologic manifestations.[ojrd.biomedcentral.com]
    Cerebellar Disease
    • disease Hereditary cerebellar syndrome with defective DNA repair G11.3 telangiectasia G11.3 (Louis-Bar) Ataxia-telangiectasia G11.3 (Louis-Bar) Boder-Sedgwick syndrome G11.3 (ataxia-telangiectasia) Louis-Bar syndrome G11.3 (ataxia-telangiectasia) Syndrome[icd10data.com]
    Delayed Development of Motor Skills
    • The first signs of the disease, which include delayed development of motor skills, poor balance, and slurred speech, usually occur during the first decade of life.[cancer.gov]
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  • Face, Head & Neck
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  • Entire body system
    Recurrent Respiratory Infections
    • This, in association with swallowing problems, makes them susceptible to recurrent respiratory infections.[kennedykrieger.org]
    • Many patients have recurrent respiratory infections.[esid.org]
    • For most (about 70 percent) of children with A-T there is another clinical hallmark: immunodeficiency that usually brings recurrent respiratory infections.[atcp.org]
    • Ataxia- telangiectasia is a rare inherited multisystem disorder that is characterised by: Ataxia (lack of co-ordination) Telangiectases on the skin and eyes Severe combined immunodeficiency resulting in recurrent respiratory infections A predisposition[dermnetnz.org]
    • Many individuals with A-T have a weakened immune system, making them susceptible to recurrent respiratory infections.[brainfacts.org]
    Falling
    • They have an increased susceptibility to infection and often fall sick with respiratory system related illnesses.[news-medical.net]
    • Signs and symptoms of Friedreich's ataxia can include: problems with balance and co-ordination, often causing wobbliness, clumsiness and frequent falls increasingly slurred, slow and unclear speech (dysarthria) increasing weakness in the legs – many people[nhs.uk]
    • All household members should receive an influenza vaccination every fall.[primaryimmune.org]
    • Truncal ataxia (oscillations of the trunk) may be evident at the 5th-6th months of life, while gait ataxia appears when the affected child starts to walk, with frequent falls.[clinicaladvisor.com]
    Cerebral Palsy
    • Persons with AT are often initially misdiagnosed as having cerebral palsy.[kennedykrieger.org]
    • A-T is a rare, neurodegenerative disease that affects children, giving them the combined symptoms of cystic fibrosis, muscular dystrophy, cerebral palsy and cancer.[globalgenes.org]
    • As toddlers, most children with A-T are thought to have a neurologic disorder such as cerebral palsy or an unspecified movement disorder.[primaryimmune.org]
    • D49 ) symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified ( R00 - R94 ) Diseases of the nervous system G11 ICD-10-CM Diagnosis Code G11 Hereditary ataxia 2016 2017 2018 Non-Billable/Non-Specific Code Type 2 Excludes cerebral[icd10data.com]
    Difficulty Walking
    • Most patients begin to have difficulty walking at the end of the first year of life and are wheelchair bound by the teenage years.[esid.org]
    • Signs and symptoms of AT can include: difficulty walking – most children need to use a wheelchair by 10 years of age increasingly slurred, slow and unclear speech (dysarthria) difficulty swallowing (dysphagia) small spider-like clusters of red blood vessels[nhs.uk]
    • Ataxia-telangiectasia (A-T) is a hereditary condition characterized by progressive neurologic problems that lead to difficulty walking and an increased risk of developing various types of cancer.[cancer.net]
    • Affected children typically develop difficulty walking, problems with balance and hand coordination, involuntary jerking movements (chorea), muscle twitches (myoclonus), and disturbances in nerve function (neuropathy).[ghr.nlm.nih.gov]
    Recurrent Infection
    • Recurrent infections, particularly sinus and respiratory - due to decreased immunoglobulin A (IgA).[patient.info]
    • Even within families, in which the specific genetic defect should be the same, some children have mostly neurologic problems while others have recurrent infections, and still others have neither neurologic problems nor recurrent infections.[healthofchildren.com]
    • In the United States, where recurrent infections typical of the disorder are usually controlled by antibiotics , patients are at high risk of developing and dying of cancer, particularly leukemias and lymphomas.[cancer.gov]
    • Mucociliary clearance is impaired following recurrent infections and aspiration, both commonly seen in A-T.[err.ersjournals.com]
    • Routine follow-up by a physician regarding immune status if an individual experiences recurrent infections.[chop.edu]
    Short Stature
    • Cockayne's syndrome ( ICD-10-CM Diagnosis Code Q87.1 Congenital malformation syndromes predominantly associated with short stature 2016 2017 2018 Billable/Specific Code POA Exempt Applicable To Aarskog syndrome Cockayne syndrome De Lange syndrome Dubowitz[icd10data.com]
    • stature and delayed puberty Mild learning problems or mild intellectual disability Smaller-than-normal cerebellum (a part of the brain), which can be seen on an MRI exam after the age of about 7 or 8 years Shortened life span (most patients live into[stjude.org]
    • stature and delayed puberty) Increased risk to develop leukemia and lymphoma and rarely other cancers The physical features associated with AT can vary in severity among individuals depending upon whether the ATM protein is completely absent or not.[chop.edu]
    • Nutritional effects on lung disease and immune function Several small cross-sectional studies have shown that patients with A-T exhibit high rates of malnutrition, short stature and reduced lean body mass [ 56 – 59 ] (E.[err.ersjournals.com]
    • Children with NBS have significant microcephaly, a distinct facial appearance, short stature, and moderate cognitive impairment, but do not experience any neurologic deterioration over time.[en.wikipedia.org]
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  • Jaw & Teeth
    Drooling
    • Loss of muscle control often leads to drooling.[counsyl.com]
    • Further features that may affect some children are insulin-resistant diabetes, premature greying of the hair, difficulty swallowing, drooling and slowed growth.[actionforat.org]
    • Supportive therapy is available to reduce the symptoms of drooling, twitching, and ataxia, but individual responses to specific medications vary.[encyclopedia.com]
    • Other features of ataxia-telangiectasia that may affect some children are:diabetes mellitus, premature graying of the hair, difficulty swallowing causing choking and/or drooling and slowed growth.[atcp.org]
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  • Workup

    The diagnosis of AT can be made firstly through physical examination, which should evaluate the presence of neurologic features, telangiectasia and infections. These should be confirmed by laboratory tests, through the detection of key abnormalities which include:

    • Elevated alpha-proteins levels, a protein playing a pivotal role in the virilization of female fetuses found in great quantities in the plasma of human fetus and in the plasma of people affected by AT.
    • Immunodeficiency associated with low levels of immunoglobulins and lymphocytes.
    • Increased sensitivity to X-ray exposure due to increased chromosomal breakage and fragility.
    • Cerebellar atrophy, which can be clearly detected by performing an MRI scan.
    • Absence or deficiency of ATM protein in cultured blood cells [19] [20].

    It would also be useful to perform a kinase assay, to detect the absence or deficiency of ATM function, and a genetic test, to detect mutations in both copies of ATM gene, even though these are not essential.

    Laboratory

    Serum
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  • Test Results

    Skin Test
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  • Treatment

    These is not a specific way to treat AT, and its treatment still remains palliative. One of the primary concerns for the patients if the presence of infections, which can be largely reduced by using antibodies. On the contrary, neurological manifestations are very hard to treat, and results remain mostly disappointing, apart from the use of beta-adrenergic blockers that might in some cases improve motor coordination.

    Physical therapy is highly recommended to maintain good muscular strength and avoid ruinous falls, which can be integrated with speech therapy in the attempt of improving the general conditions of the patients. In any case, these activities can only postpone confinement to wheelchair, which surely comes sooner or later.

    Prognosis

    AT is a progressive disease which inexorably degenerates the patient’s conditions. Patients generally find themselves wheelchair-dependent by the age of 15, even though there might be milder forms implying better clinical conditions. Signs tend to appear very early in life which later in life are followed by symptoms of spinocerebellar degeneration, like posterior cord complications or spinal muscular atrophy.

    Although classical treatment of AT might sometime give disappointing results, the new approach of the gene therapy holds great promises for patients in the future [16].

    Complications

    Cerebellar Ataxia
    • ataxia G11.2 Late-onset cerebellar ataxia G11.3 Cerebellar ataxia with defective DNA repair G11.4 Hereditary spastic paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia, unspecified G12 Spinal muscular atrophy and related syndromes G12.0[icd10data.com]
    • Home / Education / Ataxia Telangiectasia Definitive Male or female patient with either increased radiation induced chromosomal breakage in cultured cells, or progressive cerebellar ataxia, who has disabling mutations on both alleles of ATM.[esid.org]
    • Absence of mutations in ATM, the gene responsible for ataxia telangiectasia in patients with cerebellar ataxia.[appliedradiology.com]
    • Ataxia Telangiectasia [ATM]: Autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy.[jewishgeneticdiseases.org]
    • Name ataxia-telangiectasia FlyBase ID FBhh0000167 Disease Ontology Term Parent Disease OMIM Parent Disease Ontology Term This report describes ataxia-telangiectasia (AT), which is a subtype of autosomal recessive cerebellar ataxia.[flybase.org]
    Scoliosis
    • Disease Scoliosis Scoliosis is an abnormal curving of the spine.[scripps.org]
    • Scoliosis varies from mild to severe.[err.ersjournals.com]
    • Early and continued physical therapy has been proven to slow muscle degeneration and minimize contractures and scoliosis (Gatti, R., GeneReviews. 2010; ncbi.nlm.nih.gov/books/NBK26468).[preventiongenetics.com]
    • […] increasingly slurred, slow and unclear speech (dysarthria) increasing weakness in the legs – many people find walking difficult and need to use a wheelchair after around 10 to 20 years difficulty swallowing (dysphagia) abnormal curvature of the spine (scoliosis[nhs.uk]
    • Possible Complications Complications may include: Cancer, such as lymphoma Diabetes Kyphosis Progressive movement disorder that leads to wheelchair use Scoliosis Severe, recurrent lung infections When to Contact a Medical Professional Call your provider[uihc.org]
    Mental Retardation
    • Retardation and Digital Anomalies , pancreatic carcinoma , Pancreatic Neoplasms , Plummer-Vinson Syndrome , Seckel Syndrome 2 Rif1 Genetic Diseases, Inborn , Muscle Weakness , Muscular Dystrophies , Myopathies, Nemaline , Nemaline Myopathy 2 , Peripheral[rgd.mcw.edu]
    • Children with A-T usually have normal or above normal intelligence , but some cases of mental retardation have been reported.[healthofchildren.com]
    • A 25years old male patient, who were diagnosed with AT and mental retardation, was admitted to the emergency department due to fatigue, nausea and headache.[cancerindex.org]
    • Susceptibility to pulmonary infection, presence and degree of mental retardation and predisposition to leukaemia is variable in A-T and represents a tentative means of sub-classifying A-T.[doi.org]
    • Diagnosis of AT is questionable when accompanied by severe mental retardation, seizures, non-progressive ataxia, or microcephaly.[raredisorders.imedpub.com]
    Sinusitis
    • An increased risk of infections caused by bacteria and viruses is also seen in people with A-T, most commonly affecting the lungs and sinuses.[immunedisease.com]
    • […] and on their cheeks (telangiectasias) very slow eye movements, which may mean the person has to move their head a lot to compensate for this a weakened immune system – children with AT are more vulnerable to infections, particularly infections of the sinuses[nhs.uk]
    • Infections most commonly affect the lungs and/or sinuses and can be caused by bacteria and viruses.[primaryimmune.org]
    • Other findings on CT or MRI of the head include dilatation of the fourth ventricle, enlargement of the cisterna magna, and sinusitis.[appliedradiology.com]
    Hyperglycemia
    • […] absent deep tendon reflexes multiple skin changes including eczema and "coffee-with-milk"x colored spots incomplete development of tonsils, lymph nodes, and spleen (hypoplasia) seizures (any type) abnormal ovaries small testes high blood sugar levels (hyperglycemia[healthofchildren.com]
    Diabetes Mellitus
    • Other features of the disease may include mild diabetes mellitus, premature aging and graying of the hair and slowed growth.[kennedykrieger.org]
    • Other features can include premature aging (e.g. grey hair) and insulin-resistant diabetes mellitus.[preventiongenetics.com]
    • Other features of the disease may include mild diabetes mellitus, premature graying of the hair, difficulty swallowing, and delayed physical and sexual development.[brainfacts.org]
    • Some patients may develop mild case of diabetes mellitus, and so glucose levels need to be closely monitored to check for insulin levels.[news-medical.net]
    • Individuals with Ataxia Telangiectasia are also at an increased risk of developing diabetes mellitus, premature graying of the hair and delayed physical and sexual development.[disability-benefits-help.org]
    Telangiectasis
    • Ataxia-telangiectasia G11.3 (Louis-Bar) Boder-Sedgwick syndrome G11.3 (ataxia-telangiectasia) Louis-Bar syndrome G11.3 (ataxia-telangiectasia) Syndrome - see also Disease ataxia-telangiectasia G11.3 Boder-Sedgewick G11.3 Louis-Barré G11.3 Telangiectasia, telangiectasis[icd10data.com]
    • Sur syndrome progressif comprenant des telangiectasies capillaires cutanees et conjonctivales symetriques, a disposition naevoide et de troubles cerebelleux.[emedicine.medscape.com]
    • Telangiectasis is not exclusively ocular and may also appear in the butterfly regions of the face and on the ears.[doi.org]
    • Louis-Bar, D. (1941) Sur un syndrome progressif cormprenant des telangiectasies capillaires cutanees et conjonctivales symetriques, a disposition naevoide et des troubles cerebelleux, Confin.[link.springer.com]
    Bronchiectasis
    • The prevalence of bronchiectasis varied from 10% [ 17 ] to 47% [ 23 ] in these series.[err.ersjournals.com]
    • The main features are progressive cerebellar ataxia with onset in infancy; progressive telangiectasia of the bulbar conjunctivae, simulating conjunctivitis, and of the butterfly area of the face; frequent sinopulmonary infection, including bronchiectasis[pediatrics.aappublications.org]
    • These recurrent or chronic infections often lead to progressive bronchiectasis and emphysematous changes in the lungs. 10 Patients with AT have very little lymphoid tissue; hence, the presence of adenopathy is highly worrisome for malignancy.[appliedradiology.com]
    • […] individuals with classical AT have a range of respiratory complications, caused by a combination of neurological problems (in particular poor swallow and respiratory muscle weakness), immune defects (leading to respiratory tract infections and risk of bronchiectasis[acnr.co.uk]
    Leukemia
    • Heterozygous ATM mutations have also been found in some patients with T-cell prolymphocytic leukemia (T-PLL) 1 , B-cell chronic lymphocytic leukemia (B-CLL) 2, 3 and mantle cell lymphoma 4 .[cityofhope.org]
    • The primary cancer risk in AT is the development of leukemia and lymphoma.[chop.edu]
    • Of the acute leukemias, T-cell lymphoblastic leukemia (T-ALL) is by far the most common.[cancerindex.org]
    • Atm Leukemia, Biphenotypic, Acute Rnf20 Leukemia, Lymphocytic, Chronic, B-Cell Atm Leukemia, Prolymphocytic, T-Cell Atm Lipoyltransferase 1 Deficiency Nbn Lissencephaly Nbn Liver Cirrhosis Rad50 Liver Diseases, Alcoholic Psmd14 Liver Failure, Acute Atm[rgd.mcw.edu]
    • A-T also affects the immune system and increases the risk of leukemia and lymphoma in affected individuals.[medical-dictionary.thefreedictionary.com]
    Acute Leukemia
    • Treatment of acute leukemia in children with ataxia telangiectasia (A-T).[cancerindex.org]
    • Missense mutation and defective function of ATM in a childhood acute leukemia patient with MLL gene rearrangement.[ncbi.nlm.nih.gov]
    Strabismus
    • Strabismus and nystagmus may also be present.[aao.org]
    • Eye misalignments ( strabismus ) are common, but may be treatable.[en.wikipedia.org]
    • Impairment of the extrapyramidal movement system is common in A-T, as are oculomotor abnormalities such as apraxia, strabismus and nystagmus.[atlasgeneticsoncology.org]
    Cerebral Palsy
    • Persons with AT are often initially misdiagnosed as having cerebral palsy.[kennedykrieger.org]
    • A-T is a rare, neurodegenerative disease that affects children, giving them the combined symptoms of cystic fibrosis, muscular dystrophy, cerebral palsy and cancer.[globalgenes.org]
    • As toddlers, most children with A-T are thought to have a neurologic disorder such as cerebral palsy or an unspecified movement disorder.[primaryimmune.org]
    • D49 ) symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified ( R00 - R94 ) Diseases of the nervous system G11 ICD-10-CM Diagnosis Code G11 Hereditary ataxia 2016 2017 2018 Non-Billable/Non-Specific Code Type 2 Excludes cerebral[icd10data.com]
    Endocrine Dysfunction
    • Symptoms are characterized by progressive cerebellar ataxia, dysarthria, oculomotor apraxia, chorea/dystonia, oculocutaneous telangiectasias, endocrine dysfunction, immunodeficiency, premature aging, radiosensitivity, and predisposition to cancer.[scielo.br]
    • Other features include telangiectasia, immune and endocrine dysfunctions, genomic instability, premature aging, radiosensitivity, and predisposition to cancer.[dovepress.com]
    Malignant Neoplasm
    • Malignant neoplasms in the families of patients with ataxia-telangiectasia.[oncofertility.northwestern.edu]
    • Pay special attention to the susceptibility of adult members of families with ataxia-telangiectasia to malignant neoplasms and to the importance of regular examinations for early cancer detection.[emedicine.medscape.com]
    Ophthalmoplegia
    • These features include ataxia of the trunk and limbs, progressive supranuclear ophthalmoplegia, dysarthria, swallowing incoordination, facial hypomimia and delayed peripheral neuropathy.[erydel.com]
    • […] with onset in infancy; progressive telangiectasia of the bulbar conjunctivae, simulating conjunctivitis, and of the butterfly area of the face; frequent sinopulmonary infection, including bronchiectasis; and peculiarity of eye movements, simulating ophthalmoplegia[pediatrics.aappublications.org]
    Friedreich Ataxia
    • Friedreich's ataxia Friedreich's ataxia is the most common type of hereditary ataxia (caused by genes you've inherited).[nhs.uk]
    • I was diagnosed with Friedreich’s Ataxia when I was 11 years old.[ataxia.org]
    • However, Friedreich ataxia usually has a later onset.[encyclopedia.com]
    • Differential diagnosis of ataxia- telangiectasia Other inherited disorders to consider include: Friedreich ataxia Ataxia-oculomotor apraxia Familial spinocerebellar atrophy GM1 and GM2 gangliosidoses Metachromatic leukodystrophy Krabbe disease Maple syrup[dermnetnz.org]
    • Pulmonary infections Sinus infections Bulbar dysfunction Recurrent aspiration Gonadal atrophy Dystonia Chorea Sensory neuropathy Growth restriction Differential diagnosis There is a need to differentiate from other autosomal recessive ataxias: [ 13 ] Friedreich's[patient.info]
    Recurrent Pneumonia
    • Immune dysregulation in A-T can lead to recurrent pneumonia, bronchiectasis and ILD.[ojrd.biomedcentral.com]
    • pneumonia, which may progress to bronchiectasis and pulmonary fibrosis, severe enough to cause clubbing of fingers and toes, and, eventually, to respiratory insufficiency and death. 30 A-T patients are susceptible to common bacterial pathogens and viruses[doi.org]
    • In addition, diagnostic bronchoscopy may be necessary in people who have recurrent pneumonias, especially those who do not respond or respond incompletely to a course of antibiotics.[en.wikipedia.org]

    Etiology

    AT is caused by the mutations occurring in the gene of ataxia telangiectasia mutated (ATM) [3], a serine/threonine protein kinase on the chromosome 11. In particular, ATM phosphorylates several key proteins involved in the repair of double-strand DNA breaks, such as p53, CHK2 and H2AX, all examples of tumor suppressors. In other words, ATM plays a pivotal role in regulating cell response to external stressful stimuli, by recognizing the damaged DNA and activating DNA repair machinery and cell cycle checkpoints, to make sure the cell does not replicate the mutated nucleic acid sequences [4].

    Causes

    Acute Leukemia
    • Treatment of acute leukemia in children with ataxia telangiectasia (A-T).[cancerindex.org]
    • Missense mutation and defective function of ATM in a childhood acute leukemia patient with MLL gene rearrangement.[ncbi.nlm.nih.gov]

    Epidemiology

    AT can be seen in all regions of the world, with a probable incidence of 1 case in 100,000 births [5] and a frequency of around 1.4 to 2% in the general population [5] [6]. Death frequently comes from bronchopulmonary infections or malignancy, at the average age of 20 years [6]. AT has been associated with a risk of cancer ranging from 10% to 38% [7] [8] [9], a rate which is about 100 times higher than that of the general population [10].

    No difference has been found in the incidence and prevalence of AT between females and males. Furthermore, AT can been found in all races, even though the mortality ratio varies according to the ethnic group considered, perhaps due to the frequently marked difference in terms of social and economical conditions. In addition, while ataxia usually appears very soon in the first years of life, telangiectasia tends to appear later between 3 and 6 years of age.

    Sex distribution
    Age distribution

    Pathophysiology

    Although the breakpoints on the DNA are randomly distributed, chromosome rearrangements tend to affect chromosomes 7 and 14, especially around the loci of T-cell receptors and heavy-chain immunoglobulin, whose expression therefore is severely affected. This might be the reason for the high frequency of infections and neoplasias among AT subjects, which can easily occur for a marked immunodeficiency. Furthermore ATM targets include well-known tumor suppressors like p53, TP53 or BRCA 1, all plying a pivotal role in the predisposition to cancer. This might explain the consistently reported increased risk of breast cancer among women [11], which however is not associated with a consequent increased frequency for this tumor [12].

    AT has an important role in neurodevelopment, due to its proapoptotic function performed together with BAX [13], another key proapoptotic factor, which is essential during cell differentiation. AT has even been liked to accelerated telomere loss [14] [15], a mechanism believed by experts to be responsible for the other key signs of AT like neurologic disease, thymus aplasia, telangiectasias, and growth retardation. These elements taken together suggest the possible important role of AT in eliminating neurons with severe DNA damages during CNS development.

    Prevention

    Being a genetic condition, no preventive measure can be given for AT. However, families at risk are strongly recommended to have a prenatal test done.

    Summary

    Ataxia refers to the neurological sign consisting of a severe impairment of muscle movement coordination usually coupled with a gait abnormality. This condition occurs as non-specific clinical manifestation indicating serious dysfunctions of the parts of the nervous system that control movements like the cerebellum. Telangiectasia, instead, refers to small dilated blood vessels, 0.5 to 1.0 mm in diameter [1] appearing on the surface of skin, usually on the face, nose, cheeks, and chin. In other words, the subjects affected by ataxia telangiectasia (AT) show motor incoordination together with signs of telangiectasia, especially over the sclera of the eye, both of them seen as hallmarks of this particular disorder [2].

    The signs of AT generally appear during childhood, when children begin to show mobility problems and difficulties in standing still or sitting. They are soon followed by difficulties in speech and in other functions and systems, such as swallowing problems and infections of the respiratory tract, which underline the progressive pattern of this disorder.

    Patient Information

    Ataxia telangiectasia (AT) is a rare inherited neurodegenerative disorder mainly characterized by a progressive neurologic impairment together with motor incoordination. The signs of AT generally appear during childhood, when children begin to show mobility problems and difficulties in standing still or sitting. They are soon followed by difficulties in speech and in other functions and systems, such as swallowing problems and infections to the respiratory track, which underline the progressive pattern of this disorder.

    AT is caused by the mutations occurring in the gene of ataxia telangiectasia mutated (ATM), a molecule which participates in the regulation of several key proteins involved in DNA repair. In other words, ATM plays a pivotal role in regulating cell response to external stressful stimuli, by recognizing the damaged DNA and activating DNA repair machinery, to make sure the cell does not replicate mutated nucleic acid sequences.

    The name of the disorder indicates its two most important signs. Ataxia (difficulty in movement coordination) appears very soon between 3 and 5 years of age, followed by oculomotor apraxia, the difficulty in moving head and eye, together with frequent involuntary movements. These later result in more pronounced symptoms like difficulty in reading, writing, speaking or standing still, that soon end up including difficulty in eating and swallowing. Telangiectasia, that is the appearance of small dilated blood vessels of the surface of the skin, tends to appear later in life, between 5 and 8 years of age, especially on the sclera of the eye, making subjects appear bloodshot. This sign never results in bleeding or itching, and never changes or disappears in relation to time, weather or emotions.

    After this first stage the immune-related signs and complications begin to appear, like infections and increased cancer risk. Infections are the result of very low levels of lymphocytes (especially T-cells), and mainly tend to affect the respiratory track. Cancer, instead, tends to manifest itself in the form of lymphomas and leukemia, even though other forms of tumor might occur. AT is a progressive disease and patients generally find themselves wheelchair-dependent by the age of 15, even though there might be milder forms implying better clinical conditions.

    Being a genetic condition, no preventive measure can be given for AT. However, families at risk are strongly recommended to have a prenatal test done.

    Other symptoms

    Abnormal Eye Movement
    • Patients with AT develop progressive cerebellar ataxia, abnormal eye movements, other neurologic abnormalities, oculocutaneous telangiectasias, and immune deficiency.[uptodate.com]
    • eye movements ( nystagmus ) late in the disease Premature graying of the hair Seizures Sensitivity to radiation, including x-rays Severe respiratory infections that keep coming back (recurring) The health care provider will perform a physical exam.[medlineplus.gov]
    • Diagnosis of Ataxia Telangiectasia Diagnosis of A-T is generally made based on the common clinical features (ataxia, telangiectasia, abnormal eye movement and speech).[immunedisease.com]
    • Other signs that follow are deterioration of motor skills, involuntary movements, abnormal eye movements, and difficulty with speech.[actionforat.org]
    • eye movements ( nystagmus ) late in the disease Premature graying of the hair Seizures Sensitivity to radiation, including x-rays Severe respiratory infections that keep coming back (recurring) Exams and Tests The health care provider will perform a[scripps.org]
    Hypersensitivity to Ionizing Radiation
    • Return to The Medical Biochemistry Page 1996–2017 themedicalbiochemistrypage.org, LLC info @ themedicalbiochemistrypage.org Ataxia telangiectasia (AT) is an autosomal recessive disorder that is characterized by hypersensitivity to ionizing radiation,[themedicalbiochemistrypage.org]
    • Clinical manifestations of A-T include early-onset neurological alterations (cerebellar ataxia caused by Purkinje and granule cell degeneration), late-onset oculocutaneous telangiectasias, early aging, sterility, hypersensitivity to ionizing radiation[hindawi.com]
    • […] to ionizing radiation.[raredisorders.imedpub.com]
    • Cells derived from A-T patients exhibit cytoskeletal abnormalities, 4 requirements for serum growth factors and clastogenic factors, 5 , 10 , 11 chromosomal instabilities, 12 - 14 chromatin changes, 15 hypersensitivity to ionizing radiation, 16 , 17 and[bloodjournal.org]
    • Ataxia telangiectasia is a neurodegenerative inherited disease with chromosomal instability and hypersensitivity to ionizing radiation. iPS cells lacking ATM (AT-iPS cells) exhibited hypersensitivity to X-ray irradiation, one of the characteristics of[cancerindex.org]
    Caused by Mutation in the Ataxia-Telangiectasia Mutated Gene
    • Introduction Ataxia Telangiectasia (AT) is an autosomal recessive hereditary multisystem disorder with an estimated prevalence of 1:400,000 in the UK. 1,2 The disease is caused by mutations in the ataxia telangiectasia mutated gene (ATM, 11q22.3), which[acnr.co.uk]
    • […] by mutation in the ataxia-telangiectasia mutated gene (ATM).[dovepress.com]
    • J Pediatr Adolesc Gynecol. 2013; 26(2):e43-5 [ PubMed ] Related Publications BACKGROUND: Ataxia-telangiectasia is a multisystem, life-limiting, recessively inherited genetic disorder caused by mutations in the Ataxia-telangiectasia mutated gene.[cancerindex.org]
    Episodic Ataxia
    • Episodic ataxia Episodic ataxia is a rare and unusual type of hereditary ataxia where someone experiences episodes of ataxia, but the rest of the time they have no or only mild symptoms.[nhs.uk]
    Cerebellar Cortical Degeneration
    • The main underlying pathology appears to be progressive cerebellar cortical degeneration that primarily affects Purkinje and granule neurons, but also basket cells (Vinters HV et al., 1985; Gatti RA et al., 1985).[atlasgeneticsoncology.org]

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    References

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