Phenotype-Directed Testing Services for Hereditary Ataxias the More You Know, the More You Can Do
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Neurology Phenotype-Directed Testing Services Movement Disorders for Hereditary Ataxias Spinocerebellar Ataxia DRPLA Episodic Ataxia Friedreich’s Ataxia Ataxia-Telangiectasia (ATM) Ataxia with Vitamin E Deficiency Oculomotor Apraxia-Ataxia Ataxia Testing that Impacts Quality of Life. Phenotype-Directed Testing Streamlines the Path to Diagnosis Providing a conclusive diagnosis for a patient presenting Genetic Testing for Ataxia Optimizes Efficiency, with ataxia can be life-changing. Many types of acquired Economy, and Certainty or non-genetic forms of ataxia can be treated and resolved. In the cases of hereditary ataxia, establishing a molecular Only molecular genetic testing can provide a conclusive cause can provide both you and your patient with a basis for diagnosis, ending the diagnostic odyssey that is often planning support services that can extend mobility frustrating, time-consuming, and expensive. Ataxia and quality of life. It can also eliminate the need for need not be a diagnosis by exclusion. further testing. At Athena Diagnostics, we understand that you and your patients want an efficient, economical way to Need to Know obtain definitive answers. Our phenotype-directed At Athena Diagnostics®, we understand how a definitive genetic testing approach streamlines the diagnostic diagnosis can bring confidence to life-altering decisions. process for hereditary ataxia. “What’s causing my symptoms?” A Unique Approach “What treatments can help me lead a more normal life?” Guided by the clinical workup, including family history “What are the chances I will pass this on to my children?” and phenotype, ataxia genetic testing from Athena Diagnostics is organized by prevalence — starting with A Range of Possibilities the genes most likely to cause disease — progressing to the next levels of testing only as needed to achieve a Symptoms of ataxia can present almost identically yet positive result. Backed by clinical guidelines and peer- yield widely variable prognoses. Many hereditary ataxias published diagnostic algorithms, this unique approach have overlapping phenotypes that are challenging to to genetic testing allocates only the resources necessary differentiate clinically. to detect the causative mutation, avoiding over-testing and unnecessary services and expense — reducing time The differential diagnosis of hereditary ataxia can include to diagnosis and overall cost. acquired, non-genetic causes such as1 : • Alcoholism • Vitamin deficiencies • Multiple sclerosis • Vascular disease • Primary or metastatic tumors • Paraneoplastic diseases associated with occult carcinoma of the ovary, breast, or lung Phenotype-Directed Testing Services for Hereditary Ataxias The More You Know, The More You Can Do. Illuminating Answers At Athena Diagnostics, we know that finding the answer — identifying the ataxia-causing mutation and establishing the cause of disease — can empower confidence in treatments, lifestyle modifications, and personal family planning decisions. Our testing for ataxia is designed with the physician, patient, and payer in mind — for efficiency, economy, and certainty. Patient presents with imbalance, progressive gait and limb incoordination, dysarthria, and eye disturbances1 Exclude non-genetic causes: alcoholism, vitamin deficiencies, multiple sclerosis, vascular disease, primary or metastatic tumors, paraneoplastic diseases Establish family history of ataxia Consider patient phenotype Rely on Athena Diagnostics, Test for highly prevalent disease-causing genes the Leader in Genetic Testing for Neurological Disorders. Test for less prevalent disease-causing genes Continue testing as necessary to detect the causative mutation Phenotype-Directed Testing Services for Hereditary Ataxias Athena Diagnostics Phenotype-Directed Testing for Hereditary Ataxias Autosomal Dominant Family History Autosomal Recessive Family History No Family History Chorea, None, or: Normal Oculomotor Ataxia with Ataxia with Autosomal Retinal Dementia, Pure Cerebellar MRI, Peripheral Apraxia, Low Low Vitamin E High Alpha- Phenotype Pyramidal, Extra-pyramidal, or Peripheral Neuropathy Episodic Ataxia Recessive No Associated Features Dominance Inheritance Degeneration Myoclonus, Ataxia Sensory Albumin, High Levels Fetoprotein Inheritance Seizures Neuropathy Cholesterol Downbeat Typical High Nystagmus, Positioning Cerebellar Ataxia, Progressive Gait Chorea, Seizures, Serum Alpha Dementia, Diplopia, Nystagmus, Sensorimotor and Limb Ataxia, Dementia, Dementia, Fetoprotein, Slowly Progressive, Retinal Slow Saccades, Opthalmoplegia, Sometimes Neuropathy, Dysarthria, Nystagmus, Myoclonus. Recurrent Ataxia, Cerebellar Ataxia, Phenotype often associated with Degeneration, Hyporeflexia, Red-Lid Episodic Ataxia Nystagmus, Absent Deep Slow Saccades, DRPLA is often Giddiness, Ocular Apraxia, Characterization cerebellar atrophy as seen from Opthalmoplegia, Amyotrophy, Retraction, at Onset, Extrapyramidal Tendon Reflexes, Pyramidal Signs, confused with Vertigo Telangiectasias, brain imaging studies Pyramidal Signs Neuropathy, Parkinsonism, Double Vision, Signs, Mild Sensory Loss, Neuropathy Huntington Immune Defects, Myoclonus Spasticity Pyramidal Signs, Cognitive Pyramidal Disease. Predisposition Neuropathy Deep Sensory Impairment Weakness to Malignancy Loss, Migraine Age Early Childhood to Elderly 0–76 4–74 6–67 5–65 10–59 19–77 Up to 60 2–55 2–55 1–30 2–52 1–4 at Onset 6912, Oculomotor 283, Ataxia 6900, Ataxia, 6901, Ataxia, 373, SCA6 6910, Ataxia, 6901, Ataxia, 677, SCA7 371, SCA1 672, SCA2 105, SCA3 (MJD/ 401, DRPLA 349, Friedreich’s Apraxia-Ataxia with Vitamin 353, Ataxia- 6930, Ataxia, 349, Friedreich’s Complete Common Repeat (CACNA1A) 6920, Episodic Complete Common Repeat Test (ATXN7) Repeat (ATXN1) Repeat (ATXN2) Repeat ATXN3) Repeat (ATN1) Repeat Ataxia (FXN) Advanced E Deficiency Telangiectasia Comprehensive Ataxia (FXN) Dominant Expansion Repeat Ataxia Evaluation Recessive Expansion Expansion Test Expansion Test Expansion Test Expansion Test Expansion Test Evaluation Sequencing (AVED) TTPA DNA (ATM) Evaluation Evaluation Evaluation Evaluation Evaluation Expansion Test Evaluation Evaluation Evaluation Sequencing Test Genes Tested 26 Genes Tested 8 Genes Tested 1 Gene Tested 1 Gene Tested 1 Gene Tested 1 Gene Tested 1 Gene Tested 1 Gene Tested 4 Genes Tested 18 Genes Tested 1 Gene Tested 2 Genes Tested 1 Gene Tested 1 Gene Tested 43 Genes Tested 8 Genes Tested 1 Gene Tested STEP 1 Includes all Includes all Includes all Occurs mostly Most Common Most Common Gene genes known to genes known to Unknown 1:40,000 to genes known to 50-60%/AD SCA 5%/SCA 6%/SCA 15%/SCA 21%/SCA in those with 15%/SCA AR Ataxia, Rare Prevalence 50-60%/AD SCA AR Ataxia, Prevalence* cause AD SCA, cause AR SCA, Prevalence 1:100,000 cause AD and AR Asian origin 1-2:50,000 1-2:50,000 per OMIM per OMIM SCA, per OMIM 6903, Ataxia, 6911, Ataxia, 6903, Ataxia, 6911, Ataxia, Supplemental Supplemental Supplemental Supplemental Test Dominant Recessive Dominant Recessive Evaluation Evaluation Evaluation Evaluation Genes Tested 16 Genes Tested 17 Genes Tested 16 Genes Tested 17 Genes Tested STEP 2 This step Includes Includes completes remaining genes remaining genes Gene testing of all known to cause known to cause Prevalence* known AD SCA AR SCA, AR SCA, genes, per OMIM per OMIM per OMIM With an intuitive selection of tests—conveniently arranged by family history and patient phenotype—ataxias with the highest prevalence are tested first. Subsequent testing can progress to the next levels of gene prevalence on an as-needed basis until the ataxia- causing mutation is found. Test organization and content is derived from expert guidelines, publications, and consensus statements on the diagnosis of hereditary ataxias.1, 2, 3, 4 Phenotype-Directed Testing Services for Hereditary Ataxias Autosomal Dominant Family History Autosomal Recessive Family History No Family History Chorea, None, or: Normal Oculomotor Ataxia with Ataxia with Autosomal Retinal Dementia, Pure Cerebellar MRI, Peripheral Apraxia, Low Low Vitamin E High Alpha- Phenotype Pyramidal, Extra-pyramidal, or Peripheral Neuropathy Episodic Ataxia Recessive No Associated Features Dominance Inheritance Degeneration Myoclonus, Ataxia Sensory Albumin, High Levels Fetoprotein Inheritance Seizures Neuropathy Cholesterol Downbeat Typical High Nystagmus, Positioning Cerebellar Ataxia, Progressive Gait Chorea, Seizures, Serum Alpha Dementia, Diplopia, Nystagmus, Sensorimotor and Limb Ataxia, Dementia, Dementia, Fetoprotein, Slowly Progressive, Retinal Slow Saccades, Opthalmoplegia, Sometimes Neuropathy, Dysarthria, Nystagmus, Myoclonus. Recurrent Ataxia, Cerebellar Ataxia, Phenotype often associated with Degeneration, Hyporeflexia, Red-Lid Episodic Ataxia Nystagmus, Absent Deep Slow Saccades, DRPLA is often Giddiness, Ocular Apraxia, Characterization cerebellar atrophy as seen from Opthalmoplegia, Amyotrophy, Retraction, at Onset, Extrapyramidal Tendon Reflexes, Pyramidal Signs, confused with Vertigo Telangiectasias, brain imaging studies Pyramidal Signs Neuropathy, Parkinsonism, Double Vision, Signs, Mild Sensory Loss, Neuropathy Huntington Immune Defects, Myoclonus Spasticity Pyramidal Signs, Cognitive Pyramidal Disease. Predisposition Neuropathy Deep Sensory Impairment Weakness to Malignancy Loss, Migraine Age Early Childhood to Elderly 0–76 4–74 6–67 5–65 10–59 19–77 Up to 60 2–55 2–55 1–30 2–52 1–4 at Onset 6912, Oculomotor 283, Ataxia 6900, Ataxia, 6901, Ataxia, 373, SCA6 6910, Ataxia, 6901, Ataxia, 677, SCA7 371, SCA1 672, SCA2 105,