PROGRAM OPERATIONS MANUAL SYSTEMPart DI – Disability InsuranceChapter 230 – Special IssuesSubchapter 22 – Processing Quick Disability Determination (QDD) and Compassionate Allowance (CAL) in the Disability Determination Services (DDS)Transmittal No. 30, 08/20/2020
This is a CAL/QAT - no IRD or AC approval needed. (AO 40305.011).
Summary of Changes
DI 23022.665 Aicardi--Goutieres Syndrome
Updated "Description" section by removing physical signs and symptoms listed to the "Physical Findings";
Updated the "Diagnostic Testing, Physical Findings, and ICD-9-CM Coding" heading to include ICD-10-CM;
Updated "Physical Findings" by formatting to be consistent with other DI 23022 POMS; and
Added ICD-10 coding information.
DI 23022.675 Alpers Disease
DI 23022.680 Alpha Mannosidosis--Type II and III
Updated the "Diagnostic Testing, Physical Findings, and ICD-9-CM Coding" heading to include ICD-10-CM; and
Added ICD-10 coding information
DI 23022.690 Cerebrotendinous Xanthomatosis
Updated formatting of "Diagnostic Testing" sections to be consistent with other DI 23022 POMS;
DI 23022.785 Juvenile Onset Huntington Disease
DI 23022.790 Kufs Disease --Type A and B
DI 23022.795 Lissencephaly
Deleted physical signs and symptoms from the "Description" section and moving them to the "Physical Findings" section;
Updated "Diagnostic Testing" by formatting to be consistent with other DI 23022 POMS;
DI 23022.830 Myoclonic Epilepsy with Ragged Red Fibers Syndrome
DI 23022.836 Neurodegeneration with Brain Iron Accumulation - Type 1 and 2
DI 23022.845 Ohtahara Syndrome
DI 23022.850 Orthochromatic Leukodystrophy with Pigmented Glia
Defined terms in "Physical findings" section; and
DI 23022.860 Pelizaeus-Merzbacher Disease--Classic Form
Updated hyperlink for Connatal PMD;
DI 23022.865 Pelizaeus-Merzbacher Disease--Connatal Form
Updated hyperlink for Classic PMD;
DI 23022.875 Perry Syndrome
Updated "Physical Findings" by formatting to be consistent with other DI 23022 POMS;
Updated language describing physical findings in the "Physical Findings" section;
DI 23022.905 Stiff Person Syndrome
DI 23022.910 Tabes Dorsalis
DI 23022.923 Adult Onset Huntington Disease
DI 23022.925 Allan-Herndon-Dudley Syndrome
DI 23022.935 Caudal Regression Syndrome - Types III and IV
DI 23022.941 De Sanctis Cacchione Syndrome
DI 23022.949 Fatal Familial Insomnia
Provided acroynm for electroencephalography (EEG) in "Diagnostic testing" section;
DI 23022.967 MECP2 Duplication Syndrome
Updated the "Physical findings" section; and
DI 23022.973 Nonketotic Hyperglycinemia
DI 23022.977 Phelan-Mcdermid Syndrome
DI 23022.981 Roberts Syndrome
AGS; Aicardi Goutieres Syndrome; Cree Encephalitis; Encephalopathy with Basal Ganglia Calcification; Familial Infantile Encephalopathy with Intracranial Calcification and Chronic Cerebrospinal Fluid Lymphocytosis; Pseudotoxoplasmosis Syndrome; Pseudo-TORCH Syndrome
Syndrome (AGS) is a rare genetic neurodevelopmental disorder characterized by encephalopathy (brain dysfunction) that affects newborn infants and usually results in mental and physical disability. The severe early-onset form affects approximately 20 percent of infants born with AGS and is usually fatal within the first few months of life.
DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM
Diagnostic testing :
The diagnosis of AGS is established by:
Reports of genetic testing of mutations in one of five known related genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C);
Head CT showing calcification of basal ganglia and white matter +/- atrophy; or
Magnetic resonance imaging (MRI) showing leukodystrophy.
Physical findings : The signs and symptoms of AGS may include:
Peripheral spasticity (weak or stiffened muscles) ;
Truncal hypotonia (decreased muscle tone);
Poor head control;
Dystonia (involuntary muscle contractions that cause repetitive or twisting movements);
Characteristic painful itchy, red skin lesions (chilblains) on hands, feet, and ears; and
Profound intellectual disabillity.
Children with the early-onset form of AGS may have:
Hepatosplenomegaly (enlarged liver and spleen); and
Elevated liver enzymes that may mimic congenital viral infection.
Children with later-onset AGS begin having symptoms after the first weeks or monhs or normal development. Then, they may experience:
Moderate to severe developmental delay;
Loss of developmental skills;
Visual impairment; and
The prognosis of AGS depends upon the severity of symptoms and signs, and the age of onset.
SUGGESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for
Clinical history and examination that describes the diagnostic features of the impairment;
Imaging studies such as MRI/CT brain scans documenting brain abnormalities;
Molecular genetic studies and cerebrospinal fluid analysis; and
EEG results (if history suggests seizures).
Suggested Listings for Evaluation:
Alpers Syndrome; Alpers Progressive Infantile Poliodystrophy; Progressive Sclerosing Poliodystrophy; Progressive Cerebral Poliodystrophy; Diffuse Cerebral Sclerosis of Schilder
Alpers disease is a progressive, neurodevelopmental syndrome characterized by psychomotor regression (dementia), seizures, and liver disease. A mutation in the gene for the mitochondrial DNA polymerase POLG causes this disease. Most affected individuals do not show symptoms at birth and develop normally for weeks to years before the onset of symptoms.
testing : The diagnosis is established by testing for the POLG gene.
findings : The physical findings of Alpers disease may include:
Hypoglycemia secondary to underlying liver disease;
Failure to thrive;
Increased muscle tone or abnormal movements;
About 80 percent of children with Alpers disease develop symptoms in the first two years of life, and the rest develop symptoms between the ages of 2 and 25.
The prognosis is poor, with death usually occurring within ten years after diagnosis due to liver failure, cardiorespiratory failure, or unremitting seizures.
There is no cure for Alpers disease and no way to slow its progression. Treatment is symptomatic and supportive. Anticonvulsant medications may be used to treat the seizures, with usually poor medical response. Physical therapy may help to relieve spasticity and maintain or increase muscle tone.
Suggested MER for Evaluation:
Clinical history and examination that describes the progression of neurological and cognitive decline from the claimant’s medical source(s);
Laboratory tests consistent of hepatic failure; and
Activities of daily living report.
* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.
II and III
Alpha Mannosidosis Types II/III Early Onset Forms; Alpha-D- mannosidosis; Alpha-mannosidase B deficiency; Alpha-mannosidase deficiency; Lysosomal alpha B mannosidosis; Alpha B Lysosomal; Lysosomal alpha-D-mannosidase deficiency
DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING
Diagnostic testing :
A confirmed diagnosis is documented by abnormally low or absent levels of alpha-D-mannosidase enzymatic activity in white blood cells.
Cognitive and motor developmental delay or intellectual disability;
Hepatosplenomegaly (enlargement of the liver and spleen);
Long bone and joint abnormalities;
Immune dysfunction leading to frequent infections;
Facial abnormalities (e.g. prominent forehead, jaw, and flattened nose);
Distinctive facial features which may include widely spaced or unevenly developed teeth;
Thickened, enlarged tongue (macroglossia);
Flattened nasal bridge;
Protruding lower jaw (prognathism);
Strabismus or crossed eyes;
Clouding (opacity) of the transparent outer covering of the eye (cornea);
Nearsightedness (myopia); and
Type III alpha mannosidosis is the most severe form, and signs and symptoms appear in infancy with rapid progression, severe neurological deterioration, and early death. In Type II, symptoms appear before age 10, and progressive deterioration is not as rapid as in Type III. For children with Type I, symptoms appear after age 10 and progress slowly; affected children have muscle weakness but not skeletal abnormalities, and they may live well into adulthood.
There is no cure or treatment to alter the progression of alpha-mannosidosis. There are, however, symptomatic treatments that are used. For example, anticonvulsants can help to control seizures. Hearing aids improve ability to hear and communicate. Physical therapy may improve motor function, and assistive devices can aid with mobility. New and promising therapies for alpha mannosidosis include bone marrow transplantation, enzyme replacement, and gene therapy.
Clinical history and examination that describes the diagnostic features of the impairment; and
Laboratory studies of alpha D-mannosidase enzymatic activity in white blood cells
CTX; Van Bogaert-Scherer-Epstein Disease; Xanthomatosis Cerebrotendinous; Cerebral Cholesterosis; Cerebrotendinous Cholesterinosis; Cholestanol Storage Disease; Cholestanolosis; Sterol 27-hydroxylase Deficiency
Cerebrotendinous Xanthomatosis (CTX) is an inherited lipid storage disorder where the body lacks the enzyme to break down different forms of cholesterol, leading to lipid accumulation in all tissues in the central nervous system, as well as in the tendons, skin, lungs, and bones. Xanthomas (fatty yellow nodules) in the tendons begin to form in early adulthood. People with CTX are also at an increased risk of developing cardiovascular disease.
Diagnostic testing : The diagnosis of CTX is established by:
Molecular genetic testing for the CYP27A1 gene;
High cholesterol concentration;
Normal-to-low plasma cholesterol concentration;
Decreased chenodeoxycholic acid;
Increased concentration of bile alcohols and glyconjugates; and
Increased concentrations of colestanol and apolipoprotein B in cerebrospinal fluid.
Xanthomas in the Achilles tendon, patella, elbow, hand, and neck tendons;
Cataracts develop in childhood or adolescence, and xanthoma formation tends to develop in the second and third decades of life. Neurological impairments involving seizures, dementia, and involuntary reflexes and movement begin in the third decade of life and progress until death. The severity of CTX varies widely with the cause of death usually due to myocardial infarction and progressive mental deterioration.
There is no current cure for CTX. Treatment focuses on the management of disease symptoms. Cataract extraction is typically required in at least one eye by the age of 50 years. Seizures, spasticity, and parkinsonism are treated symptomatically.
Laboratory studies of CYP27A1 gene activity; and
Imaging studies such as an MRI or CT scan of the brain showing diffuse atrophy in the cerebellum, basal ganglia, and cerebrum.
Juvenile Onset Huntington Disease (JHD) is a form of Huntington disease (HD) that affects children and teenagers. Huntington disease is a hereditary neurodegenerative disorder that is characterized by progressively worsening motor, cognitive, behavioral, and psychiatric symptoms. JHD is caused by a mutation of the Huntington gene called a “CAG repeat expansion.” The mutation results in gradual neuronal degeneration in the basal ganglia of the brain, which is responsible for coordination of movements, thoughts, and emotions. As JHD progresses, other regions of the brain undergo neuronal degeneration with diffuse and severe brain atrophy that is comparable to late stage Alzheimer disease.
Diagnostic testing : The diagnosis of JHD is made by:
Clinical history documenting changes in motor, behavioral and cognitive function;
Family history of HD;
Abnormal neurologic exam findings;
Abnormal neuropsychological test results;
HD gene test with abnormal results; and
Brain imaging is optional, but if performed, may show atrophy of the caudate nucleus or (in very young children) the cerebellum, or diffuse brain atrophy.
findings: Presentation of JHD may include:
Muscle twitching (myoclonus);
Stiffness of the leg muscles;
Slurred speech; and
JHD usually has a more rapid progression rate than adult onset HD; the earlier the onset, the faster JHD progresses. Death often occurs within 10 years of JHD onset, as opposed to 10-25 years in adult onset HD.
There is no cure or treatment to stop, slow or reverse the progression of JHD. Medications may be prescribed to manage symptoms. A child psychiatrist or behavior management specialist may address behavior disorders. A speech language pathologist may evaluate communication and swallowing problems. A nutritionist may be consulted to address nutritional needs as the disease progresses. Assistive devices such as wheelchairs, helmets, and communication boards may be used for safety, and to improve quality of life.
SUGGSESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for Evaluation:
Claimant’s medical source(s) records documenting progression of motor, cognitive, and psychiatric symptoms, family history, and abnormal neurological exam findings consistent with juvenile onset HD;
Laboratory testing showing a fully-penetrant CAG repeat expansion in the HD gene (>39 CAG repeats);
Brain imaging may provide supporting evidence;
Psychological or psychiatric reports including neurocognitive testing; and
School records may provide supporting evidence.
COMPASSIONATE ALLOWANCE INFORMATION
Adult Neuronal Ceroid Lipofuscinosis; Adult Onset Neural Ceroid Lipofuscinosis; Adult NCL; NCL Type 4; NCL4; CLN4A Disease; CLN4B Disease; Kufs Disease; Kufs Type Neuronal Ceroid Lipofuscinosis
Kufs disease is an adult type of inherited neurodegenerative lysosomal storage disease (neuronal ceroid lipofuscinosis, or NCL) where abnormal fats and proteins (lipopigments) accumulate in the nervous tissue, causing progressive motor and cognitive deficits. There are two forms of Kufs disease with different but overlapping clinical manifestations:
Kufs type A, and
Kufs type B.
Diagnostic testing : The diagnosis of Kufs disease is based on:
Clinical history documenting changes in motor, behavioral, and cognitive function;
Biopsy of the skin or other tissues showing accumulation of lipopigments in cells with characteristics fingerpring-type pattern;
Electroencephalogram (EEG) documenting seizures; and
Genetic testing showing mutations. (This testing may be helpful but is not required for diagnosis.)
There are two forms of Kufs disease with different but overlapping clinical manifestations.
Myoclonus (abrupt spasms);
Ataxia (loss of coordination of the muscles);
Dysarthria (difficulties with articulation);
The clinical manifestations of Kufs disease usually appear approximately at age 30 years, but the range of onset age spans from adolescence to late adulthood. The disease is progressive and most affected individuals survive approximately ten years after onset of the symptoms.
There is no treatment to cure or slow down the progression of Kufs disease.
Anticonvulsive drugs are helpful to control seizures and myoclonic jerking.
Physical, speech, and occupational therapies, can help individuals function for as long as possible. Experimental therapies, including gene therapy, are used for NCL disorders.
Clinical history and examination that documents the diagnostic features, progressive neurological decline, and family history obtained from the claimant’s medical source(s);
EEG reports (Kufs type A);
Tissue biopsy pathology reports; and
Activities of daily living reports.
Lissencephaly Type I; LIS1; Classical Lissencephaly; X-Linked Lissencephaly; XLIS; Lissencephaly with Agenesis of the Corpus Callosum; Lissencephaly with Cerebellar Hypoplasia; Microlissencephaly; Miller-Dieker Syndrome
Lissencephaly is a brain malformation in which the physical structure of the brain did not develop correctly during fetal development. Lissencephaly is characterized by the absence of normal folds and ridges (convolutions) in the cerebral cortex, resulting in a nearly smooth brain and an abnormally small head (microcephaly).
Diagnostic testing: The diagnosis of lissencephaly is usually made by:
Computed tomography (CT), or
Magnetic resonance imaging (MRI).
Physical findings: Physical findings for lissencephaly may include:
Hypo- (loss of muscle tone) or hypertonia (increased muscle tone);
Trouble with feeding;
Poor head growth;
Difficulty controlling muscles (ataxia);
Stiffness or spasticity of arms and legs;
Slowed growth; and
The prognosis for children with lissencephaly is poor with many dying in infancy, and the remainder showing no significant development beyond a 3 -5 month level.
There is no way to reverse the effects of lissencephaly. Supportive management of lissencephaly includes treatment of seizures, and physical and occupational therapies to lessen spasticity. Feeding difficulties are treated with a gastrostomy tube. Respiratory problems are the most common causes of death.
Cranial MRI or CT scans; and
Developmental assessment or psychological testing to address allegations of mental impairment may be warranted.
MERRF; Myoclonus with Epilepsy with Ragged Red Fibers; MERRF Syndrome; Myoencephalopathy Ragged Red Fiber Disease; Fukuhara syndrome; Myoclonic epilepsy associated with ragged red fibers; Myoencephalopathy ragged-red fiber disease
Myoclonic Epilepsy with Ragged Red Fibers (MERRF) is a rare inherited neurometabolic disorder that affects the central nervous system, skeletal muscles, and other body systems. Characteristic abnormal muscle cells appear as ragged red fibers when stained and viewed under a microscope.
Diagnostic testing :
Muscle biopsy with pathology report documenting structurally abnormal mitochondria;
CT/MRI for cerebral atrophy;
EEG for seizure activity;
Blood serum testing for elevated lactate levels; and
Hearing and vision testing.
Neurological dysfunction including cerebellar ataxia;
Myoclonic seizures (brief, sudden twitching muscle spasms);
Muscle atrophy with muscle weakness;
Optic atrophy; and
Signs and symptoms of this disorder mostly appear during childhood or adolescence, although sometimes after age 20. Clinical course is variable, from slowly progressive to rapidly downhill.
There is no current cure for MERRF and treatment is supportive. Medications may be prescribed for seizures and to control muscle movement. Physical therapy and occupational therapy can be used to extend the range of muscle movement and improve dexterity. Vitamin therapies such as riboflavin, coenzyme Q, and carnitine may provide subjective improvement in fatigue and energy levels in some individuals.
Clinical history and examination that describes the diagnostic features of the impairment, and physical and cognitive findings;
Muscle biopsy showing the presence of ragged red fibers;
Imaging studies such as CT or MRI; and
EEG results, vision or hearing testing may be helpful.
NBIA-1; NBIA-2; Hallervorden-Spatz Syndrome; (HSS); Pantothenate Kinase Associated Neurodegeneration; PKAN; Pigmentary Degeneration of Globus Pallidus and Substantia Nigra Red Nucleus, Neuroferritinopathy, Infantile; Neuroaxonal Dystrophy; INAD
Neurodegeneration with Brain Iron Accumulation (NBIA) is a rare inherited neurological movement disorder that is characterized by progressive degeneration of the nervous system. NBIA Type 1 (NBIA-1) and Type 2 (NBIA-2) are caused by one or more genetic mutations that result in iron being deposited in regions of the brain that control movement and balance; the most common mutation involves the PANK2 gene.
Diagnostic testing : The diagnosis of NBIA is based on:
Medical and family history;
Neurologic exam; and
MRI of the brain can be helpful to demonstrate the accumulation of iron in the basal ganglia.
Although there are laboratory tests for the genetic mutations of NBIA-1 and NBIA-2, they are expensive and not widely available.
Physical findings: Symptoms of this disease usually develop during childhood, and may include:
Distorting muscle contractions of the limbs, face or trunk;
Involuntary writhing muscle movements;
Difficulty swallowing or speaking;
NBIA usually begins between 7 and 15 years of age, although it may also present earlier (infantile onset) or later (adult onset). The severity and rate of progression correlates with the age at onset, especially in infants and young children. Symptoms and signs such as dystonia and spasticity eventually limit the ability to walk, and usually progress to the use of a wheel chair by mid-teens. Life expectancy is variable, but the average survival after diagnosis is 10-12 years. Death can occur secondary to dystonia, impaired swallowing, and aspiration pneumonia.
There is currently no cure for NBIA. Treatment is symptomatic and supportive. Iron chelating medications have been attempted without significant effect. Individuals may benefit somewhat from pharmacological therapy for specific symptoms, such as rigidity. Physical, speech, and occupational therapies can also help with activities of daily living.
Longitudinal clinical history and examination that describe diagnostic features and family history;
Imaging studies, such as an MRI.
Early Infantile Epileptic Encephalopathy with Burst Suppression; EIEE
Ohtahara Syndrome (OS) is a rare neurological disorder characterized by onset of seizures within the first three months of life. Infants primarily have tonic seizures, but may also experience partial seizures (also called focal seizures), or myoclonic seizures. OS is most commonly caused by metabolic disorders or structural abnormalities in the brain; although for many cases, the cause cannot be determined. Most infants with the disorder show significant abnormalities of the cerebral hemispheres. Males are more often affected than females.
EEG shows the characteristic “burst suppression” pattern;
Head CT or MRI scan; and
Physical findings: Infants with OS often appear excessively sleepy with limited muscle control. As seizures become more frequent, they develop stiffness (spasticity) in the limbs.
PROGRESS I ON
OS is a very progressive seizure disorder that is associated with high mortality and morbidity. As the disease progresses, seizures become more frequent, accompanied by physical impairments and developmental delay. Some children will die in infancy within weeks or months from onset due to chest infections or pneumonia; others will have severe permanent mental and neurological deficits.
There is no cure for this disorder. Treatment is symptomatic and supportive. Anti-seizure medications are prescribed to control seizures with limited effectiveness. Corticosteroids are occasionally helpful. In cases where there is a focal abnormal area of the brain, surgery may be beneficial.
EEG with evidence of burst suppression pattern;
Metabolic laboratory studies.
ORTHOCHROMATIC LEUKODYSTROPHY WITH PIGMENTED
Pigmented Type of Orthochromatic Leukodystrophy; Pigmentary Orthochromatic Leukodystrophy; POLD; Orthochromatic Leukodystrophy with Pigmented Glia Cells; Adult Onset Leukodystrophy; Adult Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia; ALSP
Orthochromatic Leukodystrophy with Pigmented Glia is a rare inherited type of adult leukodystrophy that affect the white matter of the brain.
testing: The diagnosis of this disorder is based:
Clinical and family history;
Neuropsychological testing; and
Neuroimaging, such as computerized tomography (CT) or magnetic resonance imaging (MRI).
findings: The neurological physical findings include:
Dysarthria (weakness in the muscles used for speech);
Ocular apraxia (absence or defect of controlled, voluntary, and purposeful eye movement);
Rapidly progressive dementia; and
Facial and bulbar weakness.
Orthochromatic leukodystropy with pigmented glia is progressive and usually fatal. This disorder typically affects adults between the ages of 40-50 years of age. As the disorder progresses some individuals become wheel chair dependent and require feeding via gastrostomy to maintain nutrition and hydration. Death usually occurs within ten years of diagnosis secondary to sepsis infection.
There is no cure for this disorder. Treatment is symptom specific and supportive. Antidepressants and tranquilizers are used to treat psychiatric symptoms.
Clinical information documenting a progressive dementia is critical and required for disability evaluation of orthochromatic leukodystrophy with pigmented glia. The preferable source of this information is the clinical records from the claimant’s medical source(s); and
CT/MRI scans of the brain showing abnormal changes in the white matter.
Classic PMD; Pelizaeus-Merzbacher Brain Sclerosis; Adult Pelizaeus-Merzbacher Disease; Classic Pelizaeus-Merzbacher Disease
Pelizaeus-Merzbacher Disease (PMD) is a rare, neurodegenerative disorder, and is one of a group of genetic disorders called leukodystrophies affecting the white matter of the brain and spinal cord. There are two main types of PMD: Classic PMD and Connatal PMD. Pelizaeus-Merzbacher
Disease-Classic Form (Classic PMD) is the most common type.
Diagnostic testing: MRI demonstrates symmetric and widespread abnormality of the white matter of the cerebrum, brain stem, and cerebellum.
findings: Individuals with Classic PMD may have:
Infantile nystagmus (repetitive, uncontrolled eye movements);
Abnormal muscle tone and spasticity;
Stridor (high-pitched, whistling sound heard while taking in a breath);
Delayed motor development;
Ataxia (loss of full control of bodily movements);
Intellectual disability; and
Choreoathetosis (involuntary movements in a combination of chorea (irregular migrating contractions) and athetosis (twisting and writhing).
Classic PMD progresses slowly and children generally survive to adulthood. Some children die before the age of 20, while others live much longer.
There is no cure for PMD, and treatment is supportive. Tracheostomy and/or feeding tubes may be necessary to avoid aspiration. Physical therapy, orthotics, and antispasticity medications may aid in motor development, and minimize joint contractures and kyphoscoliosis; orthopedic surgery is sometimes indicated. Developmental therapy and special education help to maximize cognitive achievement, and speech/language therapy aids in language development.
MRI of the brain showing abnormal white matter (demyelination);
Progress reports of physical therapy, speech/language therapy; and
Reports of educational evaluations/academic progress.
Connatal Pelizaeus-Merzbacher Disease; Connatal PMD; Cockayane-Pelizaeus-Merzbacher Disease; Type II Connatal Pelizaeus-Merzbacher Disease; Severe PMD
Pelizaeus-Merzbacher Disease (PMD) is a rare, neurodegenerative disorder and is one of a group of genetic disorders called leukodystrophies affecting the white matter of the brain and spinal cord.
There are two main types of PMD: Classic PMD and Connatal PMD. Pelizaeus-Merzbacher
Disease - Connatal Form (Connatal PMD) is the most severe, with profound motor and cognitive developmental delays.
Physical findings: Individuals with Connatal PMD have:
Generalized hypotonia (decreased muscle tone); and
Nystagmus (involuntary eye movement).
Connatal PMD presents in the first month of life and is often fatal during the first decade of life, typically due to respiratory complications.
There is no cure for PMD, and treatment is supportive and symptom specific. Physical and occupational therapies are used to minimize joint contractures and dislocations. Tracheostomy may be necessary for pharyngeal weakness. Medications are prescribed for seizures and movement disorders.
MRI of the brain showing abnormal white matter (demyelination).
Parkinsonism with alveolar hypoventilation and mental depression
Perry Syndrome is a rare inherited brain disease with gradual loss of neurons that regulate movement, emotion, and breathing.
Diagnostic testing: The diagnosis of Perry syndrome is made by molecular genetic testing for DCTN1,the only gene known to be associated with Perry syndrome; and sleep studies to document abnormally slow breathing (hypoventilation)/hypoxia.
findings: Four major features characterize Perry syndrome movement abnormalities:
Weight loss; and
Signs of parkinsonism include:
Unusually slow movements (bradykinesia);
Psychiatric changes include:
Significant, unexplained weight loss affects many individuals early in the disease. Hypoventilation occurs in the later stages of the disease, and can result in a life-threatening lack of oxygen and respiratory failure.
Perry syndrome commonly presents around age 48, with the average survival of 5 years after symptoms first appear. Death is common from respiratory failure or pneumonia; suicide is another cause.
There is no cure for Perry syndrome. Treatment involves the management of symptoms, including medications for movement disorders and psychiatric symptoms; ventilatory support; and nutritional supplements.
Clinical history and examination that describes the diagnostic features of the impairment from the claimant’s medical source(s) documenting progressive physical, neurological findings of Perry syndrome; and
Sleep study results.
Stiff Man Syndrome; Stiffperson’s Syndrome; Moersch-Woltmann Syndrome; Moersch-Woltman Condition; SPS; SMS; Stiff Baby Syndrome; Focal Stiff Person Syndrome; Stiff Limb Syndrome; Jerking Stiff Person Syndrome; Progressive Encephalomyelitis with Rigidity and Myoclonus; PERM
Stiff Person Syndrome (SPS) is a rare neurological disorder with features of an autoimmune disease.
SPS is frequently associated with other autoimmune diseases such as diabetes and thyroiditis. Other diseases associated with SPS include breast cancer, epilepsy, and paraneoplatic syndrome.
Diagnostic testing: SPS is diagnosed by:
Testing profiles including anti-GAD (glutamic acid decarboxylase), antipancreatic islet cell and anti-amphiphysin antibodies;
Electroencephalogram (EEG) and lumbar puncture; and
Imaging tests are indicated only in special cases.
Physical findings: SPS is characterized by:
Muscle rigidity that waxes and wanes with painful muscle spasms;
Progressive muscle stiffness in the trunk and extremities;
Abnormal posture; and
Sensitivity to stimuli such as noise, touch, and emotional distress.
SPS may begin at any age, most commonly between 30 – 50 years of age.
Individuals with SPS may experience frequent falls with severe injuries because they lack normal defensive reflexes. SPS can occur in children including infants, although presentation is different from adults. Infants with this disorder are markedly hypertonic at birth and are at high risk of sudden infant death. In some cases, muscle tone becomes almost normal by 3 years of age, but generally reappears by adolescence.
There currently is no cure for SPS, and management focuses on relieving symptoms. Treatment may include benzodiazepine, anticonvulsant medications, intrathecal baclofen, plasmaphersis, intravenous immunoglobulin, and physical or occupational therapies. Psychiatric treatment may be considered when symptoms of depression or anxiety are prominent.
Clinical history and examination that describes the diagnostic features of the impairment, progression of neurological symptoms, response to medication, and evaluative tests that rule out other causes of stiffness;
Special antibody testing, particularly anti-GAD antibodies.
Progressive Locomotor Ataxia; Locomotor Ataxia; Syphilitic Spinal Sclerosis; Syphilitic Myelopathy
Tabes Dorsalis is a complication of untreated syphilis that damages the spinal cord and peripheral nerves.
Cerebrospinal (CSF) examination;
CT/MRI of the head and spine; and
Serum tests for syphilis infection are required to confirm the diagnosis.
Physical findings :
Myelopathy with characteristic high stepping “tabetic gait;”
Loss of coordination and balance;
Pupils that react abnormally to light;
Diminished (hyporeflexia) or absent (areflexia) reflexes;
Episodes of intense pain and disturbed sensation (paresthesias);
If left untreated, tabes dorsalis can lead to paralysis, dementia, and blindness, as well as affecting other body systems (for example, cardiovascular and musculoskeletal). Treating syphilis with antibiotics cures the infection and prevents new damage, but does not reverse the already present nerve degeneration and other complications.
Physical and occupational therapy may help people who have muscle weakness or muscle wasting. Medications may be needed to treat associated pain.
Clinical history and examination that describes the diagnostic features of the impairment and evidence of damage of the spinal cord and peripheral nervous tissue;
Laboratory reports of cerebrospinal fluid; and
Head CT, spine CT, or MRI scans of the brain and spinal cord to rule out other diseases.
ADULT ONSET HUNTINGTON DISEASE
Huntington’s chorea; Huntington’s Disease; Huntington chorea; Huntington chronic progressive hereditary chorea
Huntington disease (HD) is a hereditary neurodegenerative disorder that is characterized by progressively worsening motor, cognitive, behavioral, and psychiatric symptoms. HD is caused by a mutation of the Huntington gene called a “CAG repeat expansion.” The mutation results in gradual neuronal degeneration in the basal ganglia of the brain, and progresses to involve other regions of the brain responsible for coordination of movements, thoughts, and emotions. Neuronal degeneration causes diffuse and severe brain atrophy that is comparable to late stage Alzheimer disease.
The diagnosis of HD is made by:
Abnormal neurological exam findings;
Abnormal neuropsychological test results; and
HD gene test with abnormal results (40 or more CAG repeats).
findings: Clinical presentation of HD may include:
Changes in personality, behavior, cognition, speech, and coordination;
Random uncoordinated extremity movements (chorea);
Slowness of movement;
As the disease progresses, concentration on cognitive tasks becomes increasingly difficult, and an individual may have difficulty swallowing and feeding himself. Family history of HD is usually but not always positive.
The average onset age is around 40, plus or minus 10 years; however, onset has been documented as young as age 5 (see Juvenile HD) and as old as age 90. Death usually occurs at about 15 to 20 years after onset of symptoms, and is due to complications of the disease.
There is no cure or treatment to stop, slow or reverse the progression of HD. Claimant’s medical source(s) may prescribe medications to manage symptoms. A psychiatrist or behavior management specialist may address behavior disorders. A speech language pathologist may evaluate communication and swallowing problems. A nutritionist may be consulted to address nutritional needs as the disease progresses. Assistive devices such as wheelchairs, helmets, and communication boards may be used for safety, and to improve quality of life.
SUGGESTED PROGRAMMATIC ASSESSMENT*
Claimant’s medical source(s) records documenting progression of motor, cognitive, and psychiatric symptoms and signs; family history of HD, and abnormal neurological exam findings consistent with HD;
Laboratory testing showing a CAG repeat expansion in the HD gene (40 or more CAG repeats);
Brain imaging may provide supporting evidence; and
Psychological or psychiatric reports including neurocognitive testing.
Suggested Listings for Evaluation:
Allan-Herndon Syndrome; X-linked Intellectual Deficit with Hypotonia; Monocarboxylate Transporter 8 Deficiency; MCT8 Deficiency; MCT8 Specific Thyroid Hormone Cell Transporter Deficiency; MCT8 SLC16A2AHDS; Triidothyronine Resistence; T3 Resistence; Intellectual Disability and Muscular Atrophy; X-linked Intellectual Disability with Hypotonia
Allan-Herndon-Dudley Syndrome (AHDS) is a rare inherited disorder of brain development that causes moderate to severe intellectual disability and problems with movement. Some children with AHDS have difficulty with communication and speech. Mutations in the SLC16A2 gene (also known as MCT8)
cause AHDS. The SLC16A2 gene provides instruction for making a protein that transports thyroid hormone triiodothyronine (T3) into nerve cells during development. Because of the mutation, normal brain development is disrupted and T3 accumulates in the blood, causing toxicity in some organs and exacerbations of the symptoms of AHDS. This condition occurs exclusively in males.
testing : The diagnosis is established by a combination of clinical examination and molecular genetic testing for mutations in the SLC16A2 gene, elevated T3, and decreased T4 in the blood.
Physical findings: The physical findings of AHDS may include:
Elongation of the face;
Abnormal folding of the ears;
Abnormal muscle tone (initially hypotonia, later evolving into spasticity);
Underdevelopment of muscles (muscle hypoplasia);
Joint contractures; and
Unclear or no speech.
Children with AHDS usually appear normal at birth with signs of the disease occurring shortly after birth with poor muscle tone, inability to control head movements, and physical and developmental delays. Progressively worsening muscle weakness, stiffness, exaggerated reflexes, joint deformities, and involuntary movements of the limbs eventually leads to wheel chair dependency by early adulthood. Some children may have delays in language development.
Presently, there is no standardized treatment for AHDS. Treatment is symptom specific and supportive.
Genetic testing for mutations in the SLC16A2 (or MCT8) gene; and
Laboratory blood testing with elevations in free T3 and decreased free T4.
CAUDAL REGRESSION SYNDROME - TYPES III AND
Caudal Dysplasia Sequence; Caudal Regression Sequence; Caudal Dysgenesis Syndrome; Sacral Regression; Sacral Agenesis; Lumbo Sacral Agenesis; Sacral Defect with Anterior Meningocele; Sacral Regression Syndrome; Sacral Agenesis Syndrome
Caudal Regression Syndrome (CRS) is a rare congenital disorder that occurs when the lowest half of the body (caudal) does not fully form in utero.
There are four main types of CRS. Types I and II are considered mild forms with coccyx (tailbone) absence without deficits in functionality. Types III and IV are the most severe with systemic and neurological complications.
The exact cause of this disorder is unknown. It occurs in people with no history of the condition in their family. Multiple genetic and environmental risk factors are thought to be contributory to this condition. Maternal diabetes, genetic predisposition, and vascular hypoperfusion have been linked to CRS.
Diagnostic testing: A preliminary diagnosis can be made in utero by ultrasound, during the first trimester of pregnancy, but must be confirmed after birth. The severity of the disease is determined by examination of the newborn by postnatal ultrasound and a MRI (magnetic resonance imaging).
Physical findings :
Individuals with CRS may have:
Partial agenesis (absence) of the thoracolumbosacral spine;
Imperforate (closed) anus;
Bilateral renal dysplasia or aplasia;
In severe cases, rotation and fusion of the lower extremities;
Spinal cord defects, and related motor and sensory deficits;
Genitourinary defects (i.e. unilateral or bilateral renal absence, renal displacement, and fused urinary tubes);
Gastrointestinal defects (inability to control bowel movements and closed anus); and
The prognosis depends on the severity of spinal involvement and associated malformations. Early neonatal (the first 28 days of life) death in the severe forms occurs from cardiac, renal, and respiratory complications.
There is no cure for this disorder because the primary pathology is irreversible. Treatment is supportive and symptomatic. Individuals with severe forms of CRS require ongoing neurological, orthopedic and renal interventions. Surgical intervention, such as a colostomy is performed to treat an imperforate (closed) anus. Physical and occupational therapies are used to improve quality of life.
Clinical history and examination that describes the diagnostic features of the impairment, as well as the related functional limitations.
DE SANCTIS CACCHIONE SYNDROME
De Sanctis-Cacchione Syndrome; Xerodermic Idiocy; Xeroderma Pigmentosum with Neurological Manifestation
De Sanctis Cacchione Syndrome is a rare inherited disorder characterized by extreme sunlight sensitivity, skin atrophy and pigmentation, skin tumors, and neurological and intellectual deficits. Mutations in the ERCC6 gene cause this Syndrome. De Sanctis Cacchione Syndrome is not to be confused with Xeroderma Pigmentosum.
Diagnostic testing: Diagnosis is usually made on clinical basis; in some cases, molecular testing documenting mutations in ERCC6 gene.
findings: Physical findings include:
Photosensitivity (sun allergy);
Abnormal skin pigmentation;
Photophobia (intolerance of light);
Recurrent conjunctivitis (inflammation or swelling of the conjunctiva);
Eyelid solar lentigines (small brown pigmented spots that appear on the upper eyelids);
Skin ulceration and scarring;
Cerebellar ataxia (inability to control movements);
Progressive sensorineural deafness;
Progressive intellectual decline;
Microcephaly (abnormally small head); and
Shortening of the Achilles tendons with eventual weakness in all four limbs (quadriparesis) may be reported.
De Sanctis Cacchione Syndrome is usually diagnosed in infancy. Prognosis is generally poor.
Treatment for this disorder is symptom specific. Individuals with this condition require total protection from all forms of ultraviolet light. Examination by a dermatologist is recommended for evaluation of suspicious growths on the skin. Ophthalmological and neurological consultations are needed to address eye and neurological findings.
Laboratory findings; and
Mental testing for developmental delay or intellectual disability may be indicated.
FATAL FAMILIAL INSOMNIA
Insomnia Fatal Familial; FFI
Fatal Familial Insomnia (FFI) is a rare, genetic sleep disorder caused by prion mutation of the PRNP gene. These mutations lead to degeneration in the thalamus, the part of the brain responsible for sensory perception and regulation of motor function. FFI is characterized by by subacute onset of insomnia showing as a reduced overall sleep time, autonomic dysfunction, and motor disturbances.
Magnetic resonance imaging (MRI) of the brain;
Sleep apnea testing; and
Evidence of mutations in the PRNP gene.
High pulse and blood pressure;
Excessive sweating; and
Decline in coordination and motor ability.
FFI is a progressive sleep disorder that usually begins in adulthood and leads to death within 6 to 32 months.
There is no cure for FFI. Treatment is symptomatic and palliative.
Clinical history and examination that describes the diagnostic features of this impairment; and
Appropriate laboratory testing, including genetic testing showing mutations in the PRNP gene.
Trisomy Xq28; Distal Duplication Xq; Telomeric Duplication Xq; Lubs-Arena Syndrome; Lubs X-linked Intellectual Deficit Syndrome; Intellectual Deficit X-linked Lubs Type
MECP2 Duplication Syndrome is a genetic disorder in which there is an extra copy of the MECP2 gene on the X chromosome in each cell, meaning only males are affected. This condition causes severe neurodevelopmental disorders.
DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND
Diagnostic testing : The laboratory diagnosis of MECP 2 duplication syndrome is established by molecular genetic testing documenting duplications of Xq28, the chromosomal location of MECP 2.
Difficulties with swallowing and feeding;
Abnormal muscle tone (ranging from hypotonia to spasticity);
Poor speech development;
Recurrent respiratory infections; and
Children with this disorder appear normal at birth. Shortly after birth, infants show signs of difficulties with feeding and swallowing resulting from hypotonia, gastro-esophageal reflux, failure to thrive, developmental delay, seizures, and recurrent respiratory infections. Respiratory infections and neurological deterioration are a major cause of death, with mortality occurring in half of affected individuals by age 25.
Medical management of children with MECP 2 duplication syndrome is supportive and planned on a case-by-case basis, depending on the individual circumstances. For example, physical and occupational therapies may be used to help relieve spasticity, maintain or increase muscle tone. A speech language pathologist may evaluate communication and swallowing problems. Assistive devices such as wheelchairs, helmet, and communication boards may be used for safety, and to improve quality of life. Anticonvulsive medications may be used to treat seizures. School age children may benefit from individualized educational planning.
Clinical history and physical examination that describes diagnostic features of the impairment and laboratory findings are needed to confirm the diagnosis; and
Developmental assessment or psychological testing to address allegations of mental impairments may be warranted.
Glycine Encephalopathy; Hyperglycinemia Nonketotic; Isolated Nonketotic Hyperglycinemia; NKH; Non-ketotic Hyperglycinemia
Nonketotic Hyperglycinemia (NKH) is a genetic disorder characterized by abnormally high levels of glycine, an amino acid that is one of the “building blocks” of proteins. Glycine also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. NKH is caused by mutations in the AMT and GLDC genes, resulting in shortages of an enzyme that normally breaks down glycine in the body. This enzyme deficiency allows excess glycine to build up in tissues and organs, particularly the brain. There are several forms of NKH, which are distinguished by age of onset and severity of symptoms.
DIAGNOSTIC TESTING, PHYSCIAL FINDINGS, AND ICD-9-CM/ICD-10-CM
Diagnostic testing: A diagnosis of NKH is confirmed by:
Enzyme or DNA analysis;
Laboratory findings of elevated plasma; and
Urine and CSF (cerebral spinal fluid) glycine concentrations.
Physical findings: Individuals with NKH have:
Movement disorders (ataxia);
Hypotonia (weak muscle tone);
Spastic diplegia (spasticity in the muscles of the legs, hips, and pelvis);
Optic atrophy (damage to the optic nerves causing progressive vision loss and problems with color vision);
Developmental delays; and
Symptoms of NKH are present at birth with infants showing progressive lack of energy; feeding difficulties; weak muscle tone; abnormal jerking movements; and life threatening problems with breathing. Most children who survive these early signs and symptoms develop profound intellectual disabilities and hard to treat seizures. Mortality is associated with intractable seizures.
Treatment of NKH is symptom specific. During the first two years of life, treatment sodium benzoate to reduce plasma concentration of glycine. Other treatment consisting of antiepileptic drugs for seizures; gastrostomy tube for feeding problems and gastroesophageal reflux; and physical and occupational therapies to improve activities of daily living.
Clinical history and examination that describes the diagnostic features and physical findings; and
Abnormally elevated levels of glycine in the blood and CSF; and
Molecular genetic testing for mutations in the AMT and GLDC genes.
Phelan-McDermid Disease; Deletion 22q13 Syndrome; 22q13 Deletion Syndrome; Chromosome 22q13.3 Syndrome; Monosomy 22q13; Deletion 22q13.3 Syndrome
Phelan-McDermid Syndrome is a rare genetic disorder that involves a deletion of 22q13 or a mutation of the SHANK3 gene.
Molecular genetic testing (usually chromosome microarray analysis, or CMA); or
Fluorescent in situ hybridization (FISH) test analysis.
Physical findings: The syndrome is generally characterized by:
Neonatal hypotonia (reduced muscle tone);
Global developmental delay;
Absent to severely delayed speech;
Disproportionately large hands/feet;
Abnormal growth; and
The signs and symptoms vary widely from person to person. Some children have specific behavior characteristics including:
Mouthing or chewing non-food items;
Decreased pain perception; and
An autistic-like affect.
Individuals with Phelan-McDermid syndrome generally have life-long complications associated with this disorder with no apparent life-threatening organic malformations. Individuals surviving to adulthood may not be able to function independently and may require supportive services.
There is no cure for this disorder. Treatment is supportive and symptom specific. Physical and occupational therapies are utilized to improve adaptive functioning and strengthen muscles; and speech/language therapy is used to address delayed speech and language development. School age children require individualized and flexible instructional criteria.
Laboratory findings documenting the chromosome 22q13.3 deletion or sequencing documenting a mutation of SHANK3 (CMA or FISH testing); and
Developmental assessment or psychological testing..
Roberts Disease; Appelt-Gerken-Lenz Syndrome; Appelt-Gerken-Lenz Disease; Hypomelia Hypotrichosis Facial Hemangioma Syndrome; Hypomelia Hypotrichosis Facial Hemangioma Disease; Pseudothaliodomide Syndrome; Roberts SC Phocomelia Disease; Tetraphocomelia-Cleft-Palate Syndrome; SC Syndrome
Roberts Syndrome (RS) is a genetic disorder caused by mutations in the ESCO2 gene, resulting in abnormal chromosome separation during cell division. RS is characterized by low birth weight and subsequent growth failure, and developmental abnormalities.
Diagnostic testing: Molecular genetic testing for ESCO2 gene mutations, resulting in absence of functional ESCO2 protein.
Symmetric, shortened arm and leg bones (hypomelia), or sometimes hands and feet located very close to the body (phocomelia);
Missing toes or fingers;
Microcephaly (abnormally small head);
Micrognathia (undersized lower jaw);
Encephalocele (protrusion of the brain from the skull); and
Heart, kidney, or genital abnormalities.
There is variation in the severity of clinical manifestations, and the most severe forms of RS are often stillborn or die shortly after birth. The less severely affected may live to adulthood. Individuals with the milder form of RS may have normal intellectual and social functioning abilities. Mortality in the newborn period or early childhood is due to cardiac or renal malformations.
The treatment and management of RS is symptomatic, such as corrective surgery for cleft palate and limb deformities; prostheses, and developmental services including speech and language if cleft deformities are present. School age children require individualized and flexible instructional curricula. Standard treatment is needed for individuals with cardiac defects and renal abnormalities.
Clinical examination that describes diagnostic features of the impairment;
Molecular genetic testing for ESCO2 gene mutations; and
Developmental assessment or psychological testing.