1p36 Deletion Syndrome

Acute Leukemia

Adenylosuccinate Lyase Deficiency – Neonatal Form and Type 1

Adrenal Cancer – with Distant Metastases or Inoperable, Unresectable, or Recurrent

Adult Heart Transplant Wait List – Status Levels 1-4

Adult Non-Hodgkin Lymphoma

Adult Onset Huntington Disease

Aicardi-Goutieres Syndrome

Aicardi Syndrome

Alexander Disease (ALX) – Neonatal and Infantile

Allan-Herndon-Dudley Syndrome

Alobar Holoprosencephaly

Alpers Disease

Alpha Mannosidosis – Types II and III

ALS/Parkinsonism Dementia Complex

Alstrom Syndrome

Alveolar Soft Part Sarcoma

Amegakaryocytic Thrombocytopenia

Amyotrophic Lateral Sclerosis (ALS) – Adult

Anaplastic Adrenal Cancer – Adult with Distant Metastases or Inoperable, Unresectable, or Recurrent

Anaplastic Ependymoma

Anaplastic Thyroid Cancer

Angelman Syndrome

Angioimmunoblastic T-Cell Lymphoma

Angiosarcoma

Aortic Atresia

Aplastic Anemia

Astrocytoma – Grade III and IV

Ataxia Telangiectasia

Atypical Teratoid/Rhabdoid Tumor

Au-Kline Syndrome

Bainbridge-Ropers Syndrome

Baraitser-Winter Syndrome

Batten Disease

Beare-Stevenson Cutis Gyrata Syndrome

Beta Thalassemia Major

Bilateral Anophthalmia

Bilateral Optic Atrophy – Infantile

Bilateral Retinoblastoma

Bladder Cancer – with Distant Metastases or Inoperable or Unresectable

Blastic Plasmacytoid Dendritic Cell Neoplasm

Bohring-Opitz Syndrome

Breast Cancer – with Distant Metastases or Recurrent

CACH – Vanishing White Matter Disease – Congenital, Infantile, and Early Childhood Onset Forms

Calciphylaxis

Canavan Disease (CD)

Carcinoma of Unknown Primary Site

Cardiac Amyloidosis – AL Type

Carey-Fineman-Ziter Syndrome

CASK-Related Gene Disorders

Caudal Regression Syndrome – Types III and IV

CDKL5 Deficiency Disorder

Cerebro Oculo Facio Skeletal (COFS) Syndrome

Cerebrotendinous Xanthomatosis

Charlevoix-Saguenay Spastic Ataxia

Child Heart Transplant Wait List – Status Levels 1A/1B

Child Lymphoblastic Lymphoma

Child Lymphoma

Child Medulloblastoma

Child Neuroblastoma – with Distant Metastases or Recurrent

Cholangiocarcinoma

Chondrosarcoma – with Multimodal Therapy

Choroid Plexus Carcinoma

Chronic Idiopathic Intestinal Pseudo Obstruction

Chronic Myelogenous Leukemia (CML) – Blast Phase

CIC-rearranged Sarcoma

Coffin-Lowry Syndrome

Congenital Lymphedema

Congenital Myotonic Dystrophy

Congenital Zika Syndrome

Cornelia de Lange Syndrome – Classic Form

Corticobasal Degeneration

Costello Syndrome

Creutzfeldt-Jakob Disease (CJD) – Adult

Cri du Chat Syndrome

Degos Disease – Systemic

De Sanctis Cacchione Syndrome

Desmoplastic Mesothelioma

Desmoplastic Small Round Cell Tumors

Dravet Syndrome

Duchenne Muscular Dystrophy – Adult

Edwards Syndrome (Trisomy 18)

Eisenmenger Syndrome

Endometrial Stromal Sarcoma

Endomyocardial Fibrosis

Ependymoblastoma (Child Brain Cancer)

Erdheim Chester Disease

Esophageal Cancer

Esthesioneuroblastoma

Ewing Sarcoma

Farber Disease (FD) – Infantile

Fatal Familial Insomnia

Fibrodysplasia Ossificans Progressiva

Fibrolamellar Cancer

Follicular Dendritic Cell Sarcoma – Metastatic or Recurrent

FOXG1 Syndrome

Friedreich's Ataxia (FRDA)

Frontotemporal Dementia (FTD), Pick's Disease – Type A – Adult

Fryns Syndrome

Fucosidosis – Type I

Fukuyama Congenital Muscular Dystrophy

Fulminant Giant Cell Myocarditis

Galactosialidosis – Early and Late Infantile Types

Gallbladder Cancer

Gaucher Disease (GD) – Type 2

Gerstmann-Sträussler-Scheinker Disease

Giant Axonal Neuropathy

Glioblastoma Multiforme (Adult Brain Cancer)

Glioma – Grade III and IV

Glutaric Acidemia – Type II

GM1 – Gangliodosis – Infantile and Juvenile Forms

Harlequin Ichthyosis – Child

Head and Neck Cancers – with Distant Metastasis or Inoperable or Unresectable

Heart Transplant Graft Failure

Hematopoietic Stem Cell Transplantation

Hemophagocytic Lymphohistiocytosis – Familial Type (FHLH)

Hepatoblastoma

Hepatocellular Carcinoma

Hepatopulmonary Syndrome

Hepatorenal Syndrome

Hepatosplenic T-Cell Lymphoma

Histiocytic Malignancies

Histiocytosis Syndromes

Hoyeraal-Hreidarsson Syndrome

Hutchinson-Gilford Progeria Syndrome

Hydranencephaly

Hypocomplementemic Urticarial Vasculitis Syndrome

Hypophosphatasia – Perinatal (Lethal) and Infantile Onset Types

Hypoplastic Left Heart Syndrome

I Cell Disease

Idiopathic Pulmonary Fibrosis

Infantile Free Sialic Acid Storage Disease

Infantile Neuroaxonal Dystrophy (INAD)

Infantile Neuronal Ceroid Lipofuscinoses

Inflammatory Breast Cancer (IBC)

Intracranial Hemangiopericytoma

Jervell and Lange-Nielsen Syndrome

Joubert Syndrome

Junctional Epidermolysis Bullosa – Lethal Type

Juvenile Onset Huntington Disease

Kidney Cancer – Inoperable or Unresectable

Kleefstra Syndrome

Krabbe Disease (KD) – Infantile

Kufs Disease – Type A and B

Lafora Disease

Large Intestine Cancer – with Distant Metastasis or Inoperable, Unresectable, or Recurrent

Late Infantile Neuronal Ceroid Lipofuscinoses

Leber Congenital Amaurosis

Leigh’s Disease

Leiomyosarcoma

Leptomeningeal Carcinomatosis

Lesch-Nyhan Syndrome (LNS)

Lewy Body Dementia

Liposarcoma – Metastatic or Recurrent

Lissencephaly

LMNA-related Congenital Muscular Dystrophy

Lowe Syndrome

Lymphomatoid Granulomatosis – Grade III

Malignant Brainstem Gliomas – Childhood

Malignant Ectomesenchymoma

Malignant Gastrointestinal Stromal Tumor

Malignant Germ Cell Tumor

Malignant Migrating Partial Seizures of Infancy (MMPSI)

Malignant Multiple Sclerosis

Malignant Renal Rhabdoid Tumor

Mantle Cell Lymphoma (MCL)

Maple Syrup Urine Disease

Marshall-Smith Syndrome

Mastocytosis Type IV

MECP2 Duplication Syndrome

Megacystis Microcolon Intestinal Hypoperistalsis Syndrome

Megalencephaly-Capillary Malformation Syndrome

Menkes Disease – Classic or Infantile Onset Form

Merkel Cell Carcinoma – with Metastases

Merosin Deficient Congenital Muscular Dystrophy

Metachromatic Leukodystrophy (MLD) – Late Infantile

Metastatic Endometrial Adenocarcinoma

Microvillus Inclusion Disease – Child

Mitral Valve Atresia

Mixed Dementias

Mowat-Wilson Syndrome

MPS I

MPS II

MPS III

Mucosal Malignant Melanoma

Multicentric Castleman Disease

Multiple System Atrophy

Myelodysplastic Syndrome with Excess Blasts

Myocolonic Epilepsy with Ragged Red Fibers Syndrome

Neonatal Adrenoleukodystrophy

Neonatal Marfan Syndrome

Nephrogenic Systemic Fibrosis

Neurodegeneration with Brain Iron Accumulation – Types 1 and 2

NFU-1 Mitochondrial Disease

Nicolaides-Baraitser Syndrome

Niemann-Pick Disease (NPD) – Type A

Niemann-Pick Disease – Type C

Nonketotic Hyperglycinemia

Non-Small Cell Lung Cancer

NUT Carcinoma

Obliterative Bronchiolitis

Ohtahara Syndrome

Oligodendroglioma Brain Cancer – Grade III

OPHN1 Syndrome

Ornithine Transcarbamylase (OTC) Deficiency

Orthochromatic Leukodystrophy with Pigmented Glia

Osteogenesis Imperfecta (OI) – Type II

Osteosarcoma, Formerly Known as Bone Cancer

Ovarian Cancer – with Distant Metastases or Inoperable or Unresectable

PACS1 Syndrome

Pallister-Killian Syndrome

Pancreatic Cancer

Paraneoplastic Cerebellar Degeneration

Paraneoplastic Pemphigus

Patau Syndrome (Trisomy 13)

Pearson Syndrome

Pelizaeus-Merzbacher Disease – Classic Form

Pelizaeus-Merzbacher Disease – Connatal Form

Pericardial Mesothelioma

Peripheral Nerve Cancer – Metastatic or Recurrent

Peritoneal Mesothelioma

Peritoneal Mucinous Carcinomatosis

Perry Syndrome

Pfeiffer Syndrome – Types II and III

Phelan-McDermid Syndrome

Pineoblastoma – Childhood

Pitt-Hopkins Syndrome

Plasmablastic Lymphoma

Pleural Mesothelioma

Pompe Disease – Infantile

Pontocerebellar Hypoplasia

Posterior Cortical Atrophy

Primary Cardiac Sarcoma

Primary Central Nervous System Lymphoma

Primary Effusion Lymphoma

Primary Intracranial Malignant Melanoma

Primary Omental Cancer

Primary Peritoneal Cancer

Primary Progressive Aphasia

Progressive Bulbar Palsy

Progressive Multifocal Leukoencephalopathy

Progressive Muscular Atrophy

Progressive Supranuclear Palsy

Prostate Cancer – Hormone Refractory Disease – or with Visceral Metastases

Pulmonary Amyloidosis – AL Type

Pulmonary Atresia

Pulmonary Kaposi Sarcoma

Rasmussen Encephalitis

Refractory Hodgkin Lymphoma

Renal Amyloidosis – AL Type

Renal Medullary Carcinoma

Renpenning Syndrome

Retinopathy of Prematurity – Stage V, Bilateral

Rett (RTT) Syndrome

Revesz Syndrome

Rhabdomyosarcoma

Rhizomelic Chondrodysplasia Punctata

Richter Syndrome

Roberts Syndrome

Rubinstein-Taybi Syndrome

Salivary Cancers

Sandhoff Disease

Sarcomatoid Carcinoma of the Lung – Stages II-IV

Sarcomatoid Mesothelioma

Schindler Disease – Type I

SCN8A-related Epilepsy with Encephalopathy

Seckel Syndrome

Secondary Adenocarcinoma of the Brain

Severe Combined Immunodeficiency – Childhood

Single Ventricle

Sinonasal Cancer

Sjogren-Larsson Syndrome

Skin Malignant Melanoma – with Metastases

Small Cell Cancer of the Female Genital Tract

Small Cell Cancer of the Large Intestine

Small Cell Cancer of the Ovary

Small Cell Cancer of the Prostate

Small Cell Cancer of the Thymus

Small Cell Lung Cancer

Small Intestine Cancer – with Distant Metastases or Inoperable, Unresectable, or Recurrent

Smith Lemli Opitz Syndrome

Snijders Blok-Campeau Syndrome

Soft Tissue Sarcoma – with Distant Metastases or Recurrent

Spinal Muscular Atrophy (SMA) – Types 0 and 1

Spinal Nerve Root Cancer – Metastatic or Recurrent

Spinocerebellar Ataxia

Stiff Person Syndrome

Stomach Cancer – with Distant Metastases or Inoperable, Unresectable, or Recurrent

Subacute Sclerosing Panencephalitis

Superficial Siderosis of the Central Nervous System

SYNGAP1-Related NSID

Tabes Dorsalis

Tay Sachs Disease, Infantile Type

Taybi-Linder Syndrome

Tetrasomy 18p

Thanatophoric Dysplasia, Type 1

Thymic Carcinoma

Transplant Coronary Artery Vasculopathy

Tricuspid Atresia

Trisomy 9

Turnpenny-Fry Syndrome

Ullrich Congenital Muscular Dystrophy

Ureter Cancer – with Distant Metastases or Inoperable, Unresectable, or Recurrent

Usher Syndrome – Type I

Uveal Melanoma – with Metastases

Ventricular Assist Device Recipient – Left, Right, or Biventricular

Walker Warburg Syndrome

Warburg Micro Syndrome

WHO Grade III Meningiomas

Wolf-Hirschhorn Syndrome

Wolman Disease

Xeroderma Pigmentosum

X-Linked Lymphoproliferative Disease

X-Linked Myotubular Myopathy

Young-Onset Alzheimer’s Disease

Zellweger Syndrome

Agenesis of Corpus Callosum with Chorioretinitis Abnormality; Agenesis of Corpus Callosum with Infantile Spasms and Ocular Anomalies; Callosal Agenesis and Ocular Abnormalities; Chorioretinal Anomalies with ACC; Corpus Callosum, Agenesis of Chorioretinal Abnormality

Aicardi syndrome is an extremely rare genetic disorder characterized by a lack of a corpus callosum (tissue connecting the left and right halves of the brain), seizures, lesions on the back of the eye (retina), and other brain and eye abnormalities. This condition is present at birth and occurs almost exclusively in females. The exact cause of Aicardi syndrome is unknown, but it has been attributed to mutations in a gene located on the X chromosome.

NOTE: Aicardi syndrome is not the same as the CAL condition Aicardi Goutières syndrome. These conditions have different causes and symptoms.

Diagnostic testing: The diagnosis of Aicardi syndrome is made by:

• •

  Electroencephalogram (EEG);

• •

  Eye exam;

• •

  Computed tomography (CT) scan of the head;

• •

  Prenatal ultrasound; and

• •

  Magnetic resonance imaging (MRI).

Signs and symptoms: Signs and symptoms of Aicardi syndrome include:

• •

  Abnormality of retinal pigmentation;

• •

  Developmental delay;

• •

  Infantile spasms;

• •

  Intellectual disability;

• •

  Large ears;

• •

  Short space between upper lip and nose (philtrum);

• •

  Small head size (microcephaly);

• •

  Small, malformed hands;

• •

  Spine and rib abnormalities;

• •

  Seizures;

• •

  Partial or completely missing corpus callosum;

• •

  Sores on the retina (retinal lesions);

• •

  Microphthalmia (smaller than normal eyes);

• •

  Thin eyebrows; and

• •

  Weak, floppy, and uncoordinated muscles (hypotonia).

ICD-9: 345.1; 742.2

ICD-10: Q04.0

The severity of Aicardi syndrome varies. Some individuals with this disorder have very severe epilepsy and may not survive past childhood. Less severely affected individuals may live into adulthood with milder signs and symptoms. Aicardi syndrome is a lifelong condition without a cure. Individuals will need support throughout their life, including ongoing medical care, therapies, and other supportive services.

Treatment for Aicardi syndrome varies based on symptoms. Antiseizure medications can help regulate seizures. Sometimes, seizures are difficult to treat. There is no single medication that works well for all individuals with this condition. Implantable devices, such as a vagus nerve stimulator, may be used to help regulate brain activity. This may be an option if medication therapy management isn’t successful.

Other types of therapy may include:

• •

  Physical therapy;

• •

  Occupational therapy; and

• •

  Speech therapy.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  EEG results;

• •

  Eye examination results;

• •

  Genetic testing;

• •

  Prenatal ultrasound results; and

• •

  Results of MRI.

Suggested Listings for Evaluation:

12.05

102.02

111.02

112.05

112.14

ACTB-related Syndrome; Baraitser-Winter Syndrome 1; Baraitser-Winter Syndrome 2; BWCFF Syndrome; BWS1 Syndrome; BWS2 Syndrome; Fryns-Aftimos Syndrome

Baraitser-Winter syndrome (BWS) is a condition that affects the development of many parts of the body, particularly the face and the brain. Structural brain abnormalities are also present in most people with BWS. The most frequent brain abnormality associated with BWS is pachygyria, which is an area of the brain that has an abnormally smooth surface with fewer folds and grooves. Less commonly, affected individuals have lissencephaly, which is similar to pachygyria but involves the entire brain surface. These structural changes can cause mild to severe intellectual disability, developmental delays, and seizures. BWS is caused by autosomal dominant de novo (new) mutations in the ACTB (type 1) or ACTG1 (type 2) gene.

Diagnostic testing: The diagnosis of BWS is based on:

• •

  Clinical examination;

• •

  Symptoms;

• •

  Genetic testing for mutations in the ACTB (type 1) or ACTG1 (type 2) gene;

• •

  Magnetic resonance imaging (MRI) of the brain; and

• •

  Ophthalmology evaluation.

Physical findings: Signs and symptoms of BWS may include:

• •

  A long space between the nose and upper lip;

• •

  Bulbous nose (a nose that may appear disproportionately large) with broad nasal tip and prominent nasal bridge;

• •

  Developmental delay;

• •

  Droopy eyelids (ptosis);

• •

  Congenital nonmyopathic ptosis;

• •

  Ear abnormalities;

• •

  Abnormalities of the kidneys and urinary system;

• •

  Large eyelid opening;

• •

  Limited movements of large joints (i.e. elbows and knees);

• •

  Ocular coloboma (an area of missing tissue in the eye);

• •

  Pointed chin;

• •

  Prominent metopic ridge, and highly arched eyebrows;

• •

  Sensorineural hearing loss;

• •

  Seizures;

• •

  Short stature;

• •

  Muscle wasting in the shoulder girdle; and

• •

  Widely spaced eyes.

ICD-9: 317-319.99; 759.89

ICD-10: Q87.0; Q87.89

The prognosis for children with BWS varies depending on the severity of their symptoms. Neuromuscular involvement tends to worsen over time, with progressive muscle wasting and weakness, progressive scoliosis, osteoporosis, and loss of ambulation in the fifth decade of life.

Neurological decline with feeding difficulties and recurrent pneumonia may occur as the individual ages. Life span may be reduced due to acute ileus (functional intestinal obstruction in which muscles fail to contract causing a buildup of gas and other liquid or solid content).

Currently there is no cure for BWS. Treatment is symptomatic, involving neurological care for seizures and specialized support for developmental delays (physical/speech therapy). Abnormal vision is treated by an ophthalmologist; hearing aids may be prescribed for hearing deficits. Muscle wasting and joint limitation may require orthopedic monitoring and physical therapy to slow progressive joint ankyloses and scoliosis. Gastrointestinal (GI) disorders associated with BWS, such as intestinal malrotation, chronic intestinal pseudo-obstruction, and feeding difficulties—are primarily treated by pediatric gastroenterologists. Treatment focuses on managing the symptoms and improving the quality of life.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the clinical features of the impairment;

• •

  Genetic testing confirming gene mutations of ACTB (type 1) or ACTG1 (type 2) gene;

• •

  Neuroimaging; and

• •

  Neurological assessment.

Suggested Listings for Evaluation:

1.18

2.10

2.11

10.06

11.02

12.05

101.18

101.24

102.10

102.11

110.08B

111.02

111.09

112.05

112.14

1.15

11.07

Beare Stevenson Syndrome; Beare-Stevenson Syndrome; BSTVS; Cutis Gyrata - Acanthosis Nigricans - Craniosynostosis; Cutis Gyrata-Acanthosis Nigricans-Craniosynostosis Syndrome; Cutis Gyrata Syndrome of Beare and Stevenson

Beare-Stevenson cutis gyrata syndrome is a genetic disorder often caused by de novo (new) mutations in the FGFR2 gene. It is characterized by skin abnormalities and the premature fusion of certain bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. Airway complications are a significant concern in affected individuals.

Diagnostic testing: Diagnostic testing for Beare-Stevenson cutis gyrata syndrome may include:

• •

  Clinical evaluation;

• •

  Computerized tomography (CT) scan;

• •

  Genetic testing;

• •

  Magnetic resonance imaging (MRI);

• •

  Skin biopsies; and

• •

  X-rays.

Signs and symptoms: Signs and symptoms of Beare-Stevenson cutis gyrata syndrome may include:

• •

  Abnormality of the genitalia and anus;

• •

  Acanthosis nigricans (darkened and thickened skin);

• •

  Aplasia/hypoplasia of the earlobes;

• •

  Cloverleaf-shaped skull;

• •

  Craniosynostosis (premature closure of cranial sutures);

• •

  Cutis gyrata (excessive skin folds);

• •

  Depressed nasal bridge;

• •

  Developmental delay;

• •

  Downslanted palpebral fissures;

• •

  Ptosis (drooping upper eyelid);

• •

  Respiratory distress; and

• •

  Subcutaneous nodule (firm lump under the skin).

ICD-9: 759.89

ICD-10: Q82.8; Q84.8; Q87.8

Beare-Stevenson cutis gyrata syndrome has a very poor prognosis with most afflicted children dying before age 5. The condition is associated with a higher risk of sudden death, particularly in the first year of life. Even with appropriate medical care, death often occurs in infancy.

Most children who survive infancy have significant developmental delays and intellectual disability.

There is no cure for Beare-Stevenson cutis gyrata syndrome. Treatment is primarily supportive, based on the specific manifestations of the disorder. This may include surgical correction of craniosynostosis, treatment of ear abnormalities, and management of skin and anogenital anomalies. Regular monitoring for respiratory compromise is crucial due to the elevated risk of sudden death.

Suggested MER for Evaluation:

• •

  Clinical evaluation;

• •

  Genetic testing;

• •

  Results of imaging studies (i.e., MRI, CT scan, x-ray) to evaluate craniosynostosis; and

• •

  Skin biopsies.

Suggested Listings for Evaluation:

102.10

102.11

103.02

103.06

103.14

108.09

110.08

112.05

112.14

Listing level severity must be documented.

Bohring Syndrome; BOS Syndrome; C-Like Syndrome; Oberklaid-Danks Syndrome; Opitz Trigonocephaly-Like Syndrome

Bohring-Opitz syndrome (BOS) is an ultra-rare genetic disorder that is usually noticeable at birth. BOS is caused by a de novo (new) change to the ASXL1 gene, though it may be inherited from parents in rare cases.

BOS affects multiple body systems. Children with BOS often have severe growth restrictions, making them quite small. They may have severe developmental delay, feeding difficulties, distinctive facial features and a red or pink birthmark (nevus flammeus) on their forehead or eyelids, as well as seizures and heart anomalies. A characteristic sign of this condition is known as “BOS posture,” where the elbows are bent and the wrists angle outwards.

Some children with BOS are able to walk with the assistance of walkers or braces, but most are unable to walk independently. Additionally, children with BOS typically have significant learning differences, and most do not develop typical speech or walking abilities.

The condition is associated with a high mortality rate, and many children do not survive past 2 years old.

Diagnostic testing: BOS is diagnosed through a combination of:

• •

  Examination of characteristic clinical features including a cleft lip/palate, trigonocephaly (triangular-shaped head), glabellar/frontal nevus flammeus (red or pink birthmark on forehead), prominent eyes, unibrow, low-set ears, a high/narrow palate, truncal hypotonia, and hypertonic extremities;

• •

  Neuroimaging (magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scans; and

• •

  Sequencing of ASXL1.

If sequencing is negative, multiplex ligation-dependent probe amplification may be used.

Signs and symptoms: Signs and symptoms of BOS may include:

• •

  Severe developmental delay;

• •

  Intellectual disability;

• •

  Internal rotation of the shoulders, flexion of the elbows, ulnar deviation of wrists and/or metacarpophalangeal joints;

• •

  Distinctive facial features;

• •

  Severe neonatal feeding difficulties;

• •

  Hirsutism (excessive hair growth);

• •

  Micrognathia (abnormally small jaw);

• •

  Seizures;

• •

  Obstructive sleep apnea/sleep disturbances during infancy;

• •

  Corpus callosum defects;

• •

  Retinal and optic nerve abnormalities;

• •

  Heart defects; and

• •

  Gastrointestinal issues.

ICD-9: 759.89

ICD-10: Q87.8; Q87.89

While 50% of cases may not survive past age 2 due to respiratory/cardiac issues, some children may live into adolescence or early adulthood. Children with BOS have a high mortality rate in the first two years due to severe respiratory infections, bradycardia, and sleep apnea. The children who survive into adolescence or early adulthood typically experience persistent severe neurodevelopmental impairment, severe vision issues, and require lifelong care.

There are no specific medications or therapies for BOS. Treatment typically focuses on supportive care . Supportive treatment is usually multidisciplinary and includes physical therapy, respiratory therapy, occupational therapy, speech therapy, and feeding therapy to aid in feeding and swallowing skills.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Results of genetic testing and sequencing of ASXL1; and

• •

  Results of neuroimaging.

Suggested Listings for Evaluation:

2.09

12.05

12.11

100.05

110.08B

111.09

112.05

112.11

112.14

11.17B2

111.17

There must be a marked limitation in physical functioning and mental functioning that affects an individual’s ability to interact with others to equal listing 11.17B2.

CASK Disorders; CASK Related Intellectual Disability; CASK Related Syndrome; MICPCH Syndrome; Microcephaly with Pontine and Cerebellar Hypoplasia; X-linked Intellectual Disability XL-ID with or without Nystagmus

CASK-related gene disorders are a group of disorders affecting brain development that are caused by mutations in the CASK gene. There are two main forms:

• •

  Microcephaly with pontine and cerebellar hypoplasia (MICPCH), and

• •

  X-linked intellectual disability (XL-ID) with or without nystagmus.

CASK-related gene disorders are more commonly reported in females and include a spectrum of phenotypes that differs in females and males:

• •

  Females typically have moderate-to-severe intellectual disability, and most have progressive MICPCH. Possible findings are ophthalmologic anomalies and sensorineural hearing loss. Females who are related to males with the XL-ID nystagmus phenotype may rarely present with a mild-to-severe intellectual disability phenotype.

• •

  The spectrum in males is broad, ranging from mild XL-ID with nystagmus and additional clinical features to severe intellectual disability, MICPCH, early infantile epilepsy, and early myoclonic epilepsy.

Diagnostic testing: The diagnosis of CASK-related gene disorders is made by:

• •

  Molecular genetic testing for CASK gene mutations;

• •

  Electroencephalogram (EEG) testing;

• •

  Computed tomography (CT)/magnetic resonance imaging (MRI);

• •

  Use of multi-gene panel; or

• •

  Genomic testing.

Physical findings:

• •

  Progressive microcephaly (small head size);

• •

  Pontine hypoplasia (underdevelopment of the pons and cerebellum of the brain);

• •

  Cerebellar hypoplasia (underdevelopment of the part of the brain that controls balance and coordination);

• •

  Hypotonia (low muscle tone);

• •

  Hypertonia (stiff, rigid muscles and resistance to movement);

• •

  Seizures;

• •

  Nystagmus (rapid, uncontrollable rhythmic eye movement);

• •

  Strabismus (eyes that look in different directions);

• •

  Optic nerve hypoplasia (underdevelopment of one or both optic nerves causing vision impairment ranging from mild to blindness);

• •

  Retinopathy (non-inflammatory diseases of the retina);

• •

  Sensorineural hearing loss; and

• •

  Short stature.

ICD-9: 758.9

ICD-10: Q04.3

CASK-related gene disorders are present at birth with symptoms lasting throughout the lifetime of the individual. These disorders present with a spectrum of symptoms ranging from mild to severe.

Individuals with MICPCH usually have severe intellectual disability. They may have sleep disturbances and exhibit self-biting, hand flapping, or other abnormal repetitive behaviors. Seizures are also common in this form of the disorder.

XL-ID with or without nystagmus (rapid, involuntary eye movements) is a milder form of CASK-related intellectual disability. The intellectual disability in this form of the disorder can range from mild to severe; some affected females have normal intelligence. About half of affected individuals have nystagmus. Seizures and rhythmic shaking (tremors) may also occur in this form.

The prognosis for individuals with CASK-related gene disorders varies depending on the areas of the brain affected by the gene mutation. Degrees of cognitive impairment or intellectual disability are lifelong.

There is no cure for CASK-related gene disorders. Treatment is symptomatic and includes standard management of developmental delay and intellectual disability issues; medication for seizures; nutritional support; use of physiotherapy; and treatment of abnormal vision or hearing loss.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  EEG with evidence of burst suppression pattern;

• •

  Imaging studies such as CT or MRI;

• •

  Reports of genetic testing; and

• •

  Metabolic laboratory studies.

Suggested Listings for Evaluation:

11.02

12.05

12.11

110.08

111.02

111.09

112.05

112.11

112.14

11.07

ALTERNATE NAMES

Hepatosplenic Gamma Delta T-Cell Lymphoma; HSC

DESCRIPTION

Hepatosplenic T-cell lymphoma (HSTCL) is an extremely rare, aggressive, and very unique subtype of peripheral T-cell non-Hodgkin lymphoma (NHL). It is caused by a proliferation of cytotoxic T-cells, usually gamma delta (γδ) T-cells. In very rare occasions, the condition is caused by alpha beta (αβ) T-cells. It is characterized by rapid progression and resistance to standard chemotherapy. It typically affects the liver, spleen, and bone marrow, without involvement of lymph nodes.

HSTCL primarily affects adolescents and young adults. Males are more likely to be diagnosed than females.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Diagnostic testing for HSTCL may include:

• •

  Bone marrow, spleen, or liver biopsy;

• •

  Imaging findings, including computed tomography (CT) and positron emission tomography (PET) scan;

• •

  Liver function tests; and

• •

  F-fluorodeoxyglucose (FDG) PET/CT.

Physical findings: Individuals with HSCTL may present with:

• •

  Massive hepatomegaly (liver enlargement) and/or splenomegaly (spleen enlargement);

• •

  “B” symptoms (unexplained fevers, drenching night sweats, and significant, unintentional weight loss);

• •

  Severe hemophagocytic syndrome;

• •

  Severe fatigue;

• •

  Abdominal pain;

• •

  Jaundice (yellowing of skin);

• •

  Thrombocytopenia (low platelets);

• •

  Anemia (low red blood cells);

• •

  Neutropenia (low white blood cells); and

• •

  Lack of lymphadenopathy.

ICD-9: 202.7x

ICD-10: C86.1; C86.10

PROGRESSION

HSTCL progresses rapidly despite aggressive treatment. Individuals with HSCTL may develop hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening syndrome of extreme, uncontrollable immune activation and hyperinflammation, leading to severe organ damage and high mortality caused by dysfunctional T-cells and macrophages failing to stop immune responses. HSTCL has a poor prognosis with an estimated 5-year overall survival of less than 15%.

TREATMENT

There is no established standard of care for treatment of HSCTL. Children and adolescents with HSTCL are often treated with adult protocols. This includes high dose chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). Despite these highly intensive treatments, the prognosis for HSTCL remains poor.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Results of imaging; and

• •

  Biopsy reports.

Suggested Listings for Evaluation:

Meets

13.05A1

13.05C

113.05A1

113.05C

Equals

ALTERNATE NAMES

EPM2; Lafora Progressive Myoclonus Epilepsy; PME Type 2; Progressive Myoclonic Epilepsy Type 2; Progressive Myoclonus Epilepsy Type 2

DESCRIPTION

Lafora disease is a rare, fatal, autosomal recessive neurodegenerative disorder caused by mutations in the EPM2A or NHLRC1 (also known as EPM2B) genes leading to the accumulation of "Lafora bodies" in the brain. The disease typically presents in adolescence between ages 8 and 19. It is progressive and characterized by epilepsy with generalized tonic-clonic seizures, myoclonus, focal occipital seizures with visual symptoms, rapid cognitive decline, and dementia.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Testing to diagnose Lafora disease may include:

• •

  Electroencephalogram (EEG);

• •

  Brain magnetic resonance imaging (MRI);

• •

  Brain F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan; and

• •

  Biopsy of skin and other tissues may reveal Lafora bodies, however false positives and false negatives are common.

Targeted genetic testing of the EPM2A and NHLRC1 genes confirm the diagnosis.

Physical findings: Signs and symptoms of Lafora disease may include:

• •

  Myoclonus (sudden, involuntary muscle jerking or twitching);

• •

  Seizures;

• •

  Rapid cognitive decline;

• •

  Ataxia (problems with balance);

• •

  Dysarthria (speech difficulties);

• •

  Spasticity;

• •

  Emotional disturbances;

• •

  Memory loss and dementia; and

• •

  Occasional hallucinations.

ICD-9: 333.2; 345.1x

ICD-10: G40.C; G40.C01; G40.C09; G40.C11

PROGRESSION

The onset of Lafora disease typically occurs during late childhood or adolescence. The disease is progressive. The frequency and severity of seizures increase, often leading to status epilepticus (continuous seizure activity). Ataxia contributes to motor disability. Cognitive decline initially begins with school difficulties and progresses to dementia. Most individuals die within 10 years of symptom onset.

TREATMENT

There is no cure for Lafora disease. Treatment is palliative and focuses on managing seizures and maintaining quality of life.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Genetic testing confirming the presence of EPM2A and NHLRC1 mutations;

• •

  Results of skin and/or tissue biopsy considered in the context of the clinical findings; and

• •

  Results of brain imaging (EEG, MRI, FDG-PET).

Suggested Listings for Evaluation:

Meet

11.02

11.17

111.02

111.17

Equals

ALTERNATE NAMES

Coppola-Dulac Syndrome; EIMFS; Epilepsy of Infancy with Migrating Focal Seizures; Epilepsy with Migrating Focal Seizure in Infancy; Malignant Migrating Partial Epilepsy of Infancy; Malignant Migrating Partial Seizures of Infancy; Migrating Partial Epilepsy of Infancy; Migrating Partial Seizures of Infancy; MMPEI; MMPSI; MPEI; MPSI

DESCRIPTION

Malignant migrating partial seizures of infancy (MMPSI) is a rare, severe, and drug resistant epilepsy syndrome that starts within the first months of life. It is caused by de novo (new) mutations in genes such as KCNT1 and SCN2A. The condition is characterized by daily, nearly continuous focal seizures that "migrate" or move across both hemispheres of the brain.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Diagnostic testing for MMPSI may include:

• •

  Electroencephalograph (EEG);

• •

  Brain magnetic resonance imaging (MRI);

• •

  Magnetic resonance spectroscopy (MRS); and

• •

  Molecular genetic testing.

Physical findings: Signs and symptoms of MMPSI may include:

• •

  Focal motor, tonic, or clonic seizures, often with autonomic symptoms (e.g., breath-holding, flushing, cyanosis);

• •

  Acquired microcephaly;

• •

  Spasticity;

• •

  Axial hypotonia (weakness of the neck/trunk);

• •

  Profound psychomotor regression;

• •

  Athetosis (involuntary writhing); and

• •

  Strabismus (crossed eyes) and rapid eye blinking or, less commonly, tonic eye deviation.

ICD-9: 345.40; 345.41; 345.50; 345.51; 345.9

ICD-10: G40.00; G40.009; G40.101; G40.109

PROGRESSION

Children with MMPSI begin experiencing seizures during the first six months of life, typically in the neonatal period. MMPSI has a marked drug resistance. Neurological status of children with MMPSI progressively deteriorates with worsening seizures.

MMPSI has a very poor prognosis, and many affected children do not survive childhood. Most affected children develop microcephaly by 1 year of age in addition to severe intellectual disabilities, inability to use language (aphasia).

TREATMENT

Currently, there are no anti-seizure medications that have been proven to reduce seizure frequency and duration.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Results of imaging; and

• •

  Results of genetic testing.

Suggested Listings for Evaluation:

Meets

111.02

112.02

112.05

112.14

Equals

Billuart-type X-linked Intellectual Developmental Disorder; MRX60; MRXSBL; Oligophrenin-1 Syndrome; Oligophrenin-1 Syndrome / OPHN1 Deficiency; Oligophrenin-1; OPHN1 Deficiency; OPHN1 Neurodevelopmental Disorder; OPHN1 Related XLID; OPHN1-related Syndrome; X-linked Intellectual Disability 60; X-Linked Intellectual Disability-Cerebellar Hypoplasia Syndrome

OPHN1 syndrome is a rare disorder characterized by intellectual disability and changes in the part of the brain (cerebellum) which controls movement, balance, and motor skills. Affected individuals may have moderate to severe intellectual disability, low muscle tone (hypotonia), developmental and cognitive delay, early-onset seizures, abnormal behavior, small or underdeveloped genitals, characteristic facial features (long face, bulging forehead, under eye creases, deep-set eyes, and large ears), crossed eyes (strabismus), and inability to coordinate movements. OPHN1 syndrome mainly affects males who usually show the full, often severe range of symptoms due to having only one X chromosome. Females are generally carriers of the genes that cause OPHN1 syndrome and tend to show milder features of the syndrome, such as mild learning difficulties or slight facial differences. OPHN1 syndrome is caused by mutations in the OPHN1 gene.

Diagnostic testing: The diagnosis of OPHN1 syndrome is based on:

• •

  Clinical evaluation;

• •

  Clinical phenotype (observable, measurable, and physical features) in males;

• •

  Carrier detection in females;

• •

  Molecular genetic testing for mutations in the OPHN1 gene;

• •

  Magnetic resonance imaging (MRI) imaging of the brain;

• •

  Next generation sequencing panels for intellectual disability; and

• •

  Chromosomal microarray.

Physical findings: Signs and symptoms of OPHN1 syndrome may include:

• •

  Early-onset epilepsy;

• •

  Hypotonia (low muscle tone);

• •

  Cerebellar hypoplasia;

• •

  Characteristic facial features (i.e., long face, bulging deep-set eyes, prominent forehead);

• •

  Infraorbital (the region below the eye socket) creases;

• •

  Large ears;

• •

  Long tubular nose;

• •

  Strabismus (crossed eyes);

• •

  Nystagmus (involuntary rapid and repetitive eye movements); and

• •

  Genital hyperplasia in males.

ICD-9: 319; 759.89

ICD-10: Q04.3

The symptoms of OPHN1 syndrome may start to appear in neonatal/infants and early childhood with symptoms of severe neonatal hypotonia (low muscle tone), motor delays, and treatment resistant seizures. Some males may exhibit moderate to severe neurological degeneration, with some, but not all, having autism spectrum disorder. The severity of intellectual disability and behavioral issues varies.

Currently, there is no cure for OPHN1 syndrome. Treatment focuses on supportive care to improve quality of life, maximize function, and reduce complications. Treatment is symptom specific and involves the management of intellectual disability and cerebellar hypoplasia. Occupational therapy, physical therapy, and speech therapy are recommended to address developmental delays.

Suggested MER for Evaluation:

• •

  Clinical history and physical examination that describes the diagnostic features of the impairment;

• •

  Genetic sequencing tests confirming mutation of the OPHN1 gene; and

• •

  MRI imaging of the brain.

Suggested Listings for Evaluation:

12.02

12.05

12.10

12.11

110.08

111.02

112.02

112.05

112.10

112.11

112.14

Advanced Uveal Melanoma; Choroidal Melanoma Metastasis; Ciliary Body Melanoma Metastasis; Hepatic Metastases of Uveal Melanoma; Intraocular Melanoma; Iris Melanoma Metastasis; Metastatic Ocular Melanoma; Metastatic UM; Metastatic Uveal Melanoma; mUM; Ocular Melanoma Metastases; Secondary Eye Cancer; Stage 4 Ocular Melanoma; Stage 4 Uveal Melanoma; Stage IV Ocular Melanoma; Stage IV Uveal Melanoma

Uveal melanoma (UM) is a rare cancer of the pigment producing cells (melanocytes) located in the middle layer of the eye known as the uveal tract or uvea. Uveal melanoma with metastases occurs when there is metastases (spread) to adjacent skin or distant sites such as the liver, lungs, or brain.

The uveal tract has three parts: the iris (colored part of the eye), the ciliary body (the ring of muscle tissue that changes the size of the pupil and the shape of the lens), and the choroid (the vascular layer located behind the retina). The UM tumors that occur in the eye are:

Choroidal melanoma is the most common form of UM. This form is more likely to metastasize if it is diagnosed at a later stage. It can spread to other parts of the body, but it typically spreads to the liver.

Ciliary body melanoma is the second most common type of UM. It occurs when the tumor originates in the ciliary body and often grows for a long time before diagnosis, so tumors are usually larger when found. This type of UM is more likely to spread to other parts of the body, often to the liver.

Iris melanoma originates in the iris. It is the least common type of UM. These tumors are often visible, slow-growing, and usually have a better prognosis than the other types of UM. Iris melanoma rarely spread outside of the eye. There is no staging system for iris melanoma.

Although UM is classified as a melanoma, the disease is distinctly different than other skin (cutaneous) melanomas. The mutations found in UM cells are different from those found in other melanoma subtypes. It is characterized by different genetic mutations, the location of mutated cell origin, no connection to sun exposure, and the high likelihood of metastases to the liver through the bloodstream instead of the lymphatic system.

The exact cause of UM is unknown. It is believed to be caused by mutations in the BAP1, EIF1AX, GNA11, GNAQ, and SRSF2/SF3B1 genes.

Diagnostic testing: The diagnosis of metastatic UM is made by:

• •

  Abdominal/chest computed tomography (CT);

• •

  Blood tests;

• •

  Eye examination;

• •

  Fine needle aspiration biopsy

• •

  Fluorescein angiography

• •

  Fundus photography;

• •

  Laparoscopy;

• •

  Liver function tests;

• •

  Magnetic resonance imaging (MRI) with contrast;

• •

  Ocular ultrasound;

• •

  Ophthalmoscopy;

• •

  Optical coherence tomography (OCT); and

• •

  Ultrasound of affected organ(s).

Physical findings: The symptoms of metastatic UM depend on the location of the tumor and how long it has been there. Individuals with metastatic UM may experience:

• •

  Bone pain or tenderness;

• •

  Chest pain;

• •

  Cough;

• •

  Enlarged liver;

• •

  Fatigue;

• •

  Fractures;

• •

  Jaundice;

• •

  Loss of appetite;

• •

  Lumps or spots under the skin;

• •

  Nausea;

• •

  Persistent cough;

• •

  Shortness of breath;

• •

  Sweats and fever;

• •

  Unintended weight loss;

• •

  Upper right abdominal pain; and

• •

  Weight loss.

ICD-9: 190.0 ; 190.6; 190.9

ICD-10: C69.3; C69.4; C69.40; C69.90

Over half of individuals with a diagnosis of UM will develop metastatic UM. It is aggressive and spreads quickly, typically to the liver, however it can also spread to the bones, lungs, lymph nodes, kidneys, skin, and soft tissue. This spread can happen years after the initial diagnosis, sometimes decades later. The metastatic tumor is the same type of cancer as the primary tumor from the first diagnosis. For example, if UM spreads to the liver, the cancer cells in the liver are actually UM cells. The disease is metastatic UM, not liver cancer.

Metastatic UM can occur at any age, but it is most often diagnosed in adults between 50 and 70 years old. Risk factors include light-colored eyes, fair skin, dysplastic nevus syndrome (numerous, abnormal looking moles), atypical or common cutaneous nevi (moles), and family history.

The prognosis is extremely poor, with overall survival ranging from three to 12 months after diagnosis of metastases.

The treatment of UM depends on the size and location of metastatic tumors. Treatment focuses on managing symptoms and improving quality of life. In most cases treatment will be used to prolong life but will not likely result in cure.

Treatment depends on the size and location of the metastases and may consist of both systematic and local therapy. These may include:

• •

  Biological response modifier (BRM) therapy;

• •

  Chemotherapy;

• •

  Clinical trials;

• •

  Embolization;

• •

  Enucleation;

• •

  Hepzato Kit;

• •

  Hormonal therapy;

• •

  Immunotherapy;

• •

  Liver-directed therapy;

• •

  Radiation therapy;

• •

  Radiofrequency ablation (RFA);

• •

  Surgical resection of the tumor(s);

• •

  Targeted therapy; and

• •

  Tebentafusp-tebn.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Biopsy results; and

• •

  Results of imaging studies (i.e., MRI, CT scan, ultrasound) showing evidence of metastases.

Suggested Listings for Evaluation:

13.29B3

Malignant melanoma with metastases

Micro Syndrome; WARBM; Warburg-Sjo-Fledelius Syndrome

Warburg micro syndrome (WARBM) is an extremely rare genetic disorder that primarily affects the development of the eyes, brain, and endocrine system. It is characterized by severe intellectual disability and progressive neurological decline beginning in infancy. WARBM is caused by mutations in the RAB3GAP1, RAB3GAP2, RAB18, or TBC1D20 genes.

Diagnostic testing: The diagnosis of WARBM is made by:

• •

  Clinical evaluation/examination;

• •

  Molecular genetic testing to identify mutations in the RAB3GAP1, RAB3GAP2, RAB18, or TBC1D20 genes; and

• •

  Brain magnetic resonance imaging (MRI).

Physical findings:

• •

  Congenital cataracts;

• •

  Microphthalmia (one or both eyes abnormally small);

• •

  Small pupils;

• •

  Optic atrophy;

• •

  Developmental delay;

• •

  Progressive spastic diplegia;

• •

  Seizures;

• •

  Brain abnormalities such as corpus callosum hypoplasia, polymicrogyria, and cortical atrophy;

• •

  Microcephaly (small head circumference);

• •

  Cryptorchidism/micropenis in males and hypoplastic genitalia in females; and

• •

  Facial features with wide nasal bridge, deep set eyes, and narrow mouth.

ICD-9: 759.89

ICD-10: Q87.0; Q87.89

Signs and symptoms of WARBM are present in early infancy, with progressive neurological decline. Individuals with WARBM have severe intellectual disability and other neurological features due to problems with growth and development of the brain. Affected individuals have delayed development and may never be able to sit, stand, walk, or speak. They usually have weak muscle tone (hypotonia) in infancy. By early childhood, they develop muscle stiffness (spasticity) and joint deformities (contractures) that restrict movement in the legs. The muscle problems worsen (progress) to include the arms and lead to paralysis of all four limbs (spastic quadriplegia). Eventually, breathing may be impaired. Brain abnormalities can contribute to vision problems (cortical visual impairment). Individuals with WARBM may also have recurrent seizures (epilepsy).

There is no cure for WARBM . Management is symptom specific and supportive. Antiepileptic medication is used for seizures; physical therapy/occupational therapy is used to address spasticity, contractures and severe developmental delay; surgery is used to remove congenital cataracts, and hormone treatments are used to address hypogonadism (small/undescended testes or delayed puberty).

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Genetic sequencing tests confirming mutation of the RAB3GAP1, RAB3GAP2, RAB18, or TBC1D20 genes;

• •

  Ophthalmologic evaluation reports of visual acuity; and

• •

  Results of MRI of the brain.

1.18

2.02

11.02

11.07

12.02

12.05

101.18

101.24

102.02

110.08

111.02

111.07

112.02

112.05

112.14

11.07

111.07

ALTERNATE NAMES

Cardiac Angiosarcoma; Heart Sarcoma; Malignant Heart Tumor; Primary Cardiac Tumor

Cardiac sarcoma is a rare type of primary malignant (cancerous) tumor that occurs in the heart. Primary cardiac sarcoma are extremely rare malignant tumors that start in the heart. Primary cardiac sarcoma is often diagnosed late. It is known to proliferate rapidly and generally carries a poor prognosis despite aggressive treatment. Cardiac tumors can occur at any age. However, primary cardiac sarcomas are more common in middle-aged adults.

The most common type of primary cardiac sarcoma is angiosarcoma. Other types of primary cardiac sarcoma include leiomyosarcoma, malignant fibrous histiocytoma, myxoma, rhabdomyosarcoma, and synovial sarcoma.

NOTE: Angiosarcoma, leiomyosarcoma, and rhabdomyosarcoma are CAL conditions. Evaluate claims for these conditions using the guidance provided in their impairment summaries.

Diagnostic testing: A diagnosis of primary cardiac sarcoma is confirmed by:

• •

  Transthoracic echocardiogram (TTE);

• •

  Transesophageal echocardiogram (TEE);

• •

  Electrocardiogram (ECG/EKG);

• •

  Cardiac magnetic resonance imaging (MRI);

• •

  Computed tomography (CT) scan;

• •

  Chest x-ray;

• •

  Positron emission tomography (PET) scan;

• •

  Biopsy; and

• •

  Cardiac catheterization/angiography.

Physical findings: Signs and symptoms of primary cardiac sarcoma may include:

• •

  Obstruction of the right atrium;

• •

  Swelling of feet, legs, ankles, and/or abdomen;

• •

  Increased fluid around the heart;

• •

  Chest pain;

• •

  Shortness of breath;

• •

  Fatigue;

• •

  Palpitations;

• •

  Hemoptysis (coughing up blood);

• •

  Heart rhythm problems;

• •

  Upper facial congestion;

• •

  Fever;

• •

  Weight loss;

• •

  Night sweats;

• •

  Malaise (fatigue, tiredness);

• •

  Fingers that change color or turn blue when pressure is applied; and

• •

  Nail curvature with enlargement of fingers.

ICD-9: 164.1

ICD-10: C38.0

While most cardiac tumors are benign, primary cardiac sarcomas are aggressive with a higher risk of metastasis and shorter survival rates compared to other soft tissue sarcomas.

Once primary cardiac sarcoma has progressed to the point that symptoms begin to occur, it has often metastasized (spread) to other parts of the body, making the associated treatment challenging. The type of treatment for primary cardiac sarcoma depends largely on the location and size of the tumor as well as the extent of metastasis. Types of treatment for primary cardiac sarcoma may include heart transplantation, open heart surgery, or autotransplantation.

If metastasis has occurred, radiation therapy or chemotherapy may be given to help relieve symptoms or improve quality of life.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Results from cardiac imaging; and

• •

  Biopsy results.

4.09

13.04A or B

Meets listing 4.09 only if heart transplant surgery has been performed.

Malignant Melanoma of Meninges; Meningeal Melanomatosis – Diffuse Type - Primary Intracranial Malignant Melanoma; Primary CNS Melanoma; Primary Intracranial Leptomeningeal Melanomatosis; Primary Intracranial Melanocytic Neoplasm; Primary Leptomeningeal Melanoma; Primary Melanocytic Tumor; Primary Melanoma of the Central Nervous System; Primary Melanoma of the Meninges

Primary intracranial malignant melanoma (PIMM) is an extremely rare, aggressive brain malignancy that emerges from the melanocytes lining tissue that surrounds the brain and spinal cord. PIMM lacks specific symptoms and often mimics meningioma on imaging. They are like melanomas of other sites and are diagnosed after melanoma brain metastases have been ruled out. It accounts for approximately 1% of all melanomas and 0.07% of all brain malignancies. PIMM rarely spreads beyond the central nervous system (CNS).

Diagnostic testing: The diagnosis of PIMM is made by:

• •

  Cerebrospinal fluid cytopathology;

• •

  Dermatological skin exam;

• •

  Eye examination;

• •

  Full-body screening;

• •

  Histopathology;

• •

  Magnetic resonance imaging (MRI)/computed tomography (CT);

• •

  Pathology reports; and

• •

  Surgical tissue biopsy.

Physical findings:

• •

  Raised intracranial pressure;

• •

  Headaches;

• •

  Focal neurological symptoms related to tumor location;

• •

  Seizures or subarachnoid hemorrhage;

• •

  Spinal tumor;

• •

  Back pain;

• •

  Muscle weakness;

• •

  Numbness;

• •

  Plegia (a kind of paralysis); and

• •

  Urinary incontinence.

ICD-9: 191.0-191.9; 192.1

ICD-10: C70.9

PIMM is highly aggressive, infiltrating, and responds poorly to treatments. The prognosis is poor due to high recurrence, with an average survival of 23 months with a three-year survival rate of only 13%.

Treatment of PIMM consists of a combination of surgical resection, adjuvant (post-surgical) radiation, and chemotherapy. Targeted immunotherapy may also be used.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Pathology reports of the cancer biopsy or surgical specimen are the critical information necessary for disability evaluation;

• •

  Operative reports; and

• •

  Results of neuroimaging (e.g. CT, MRI).

Suggested Listings for Evaluation:

Meets

Equals

13.29C

Adenylosuccinase Deficiency; Adenylosuccinate Lyase Deficiency Neonatal Form; Adenylosuccinate Lyase Deficiency Type 1; ADSLD; ADSL Deficiency; ADSL Deficiency Type 1; Succinylpurinemic Autism

Adenylosuccinate lyase deficiency (ADSL deficiency) is a rare metabolic disorder caused by mutations in the ADSL gene and is inherited in an autosomal recessive fashion. It is characterized by developmental delay, seizures, learning/intellectual disability, and autism related behaviors.

The most severe forms of ADSL deficiency, based on the severity of the signs and symptoms, are:

• •

  Neonatal form (most severe); and

• •

  ADSL deficiency type 1 (severe and most common).

Neonatal form: The most severe type, with an onset from birth. It presents with fatal neonatal encephalopathy with a lack of spontaneous movement, respiratory failure, and intractable seizures resulting in early death within the first weeks of life.

ADSL deficiency type 1: Presents in infancy or early childhood with a purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features.

NOTE: ADSL deficiency type 2 is the moderate or mild form and has a later onset, usually within the first years of life, with slight to moderate psychomotor retardation and transient contact disturbances and will be evaluated on a case-by-case basis.

Prognosis for ADSL deficiency in the neonatal and type 1 forms is poor.

Newborns with the neonatal form of ADSL deficiency have severe encephalopathy, which leads to a lack of movement, difficulty feeding, and life-threatening respiratory problems. Some affected newborns develop seizures that do not improve with treatment. Because of the severity of the encephalopathy, infants with this form of the condition generally do not survive more than a few weeks after birth.

Infants with ADSL deficiency type 1 develop recurrent seizures that are difficult to treat, and some exhibit autistic traits, such as repetitive actions and a lack of eye contact.

Currently, there is no cure for any forms of ADSL deficiency. Treatment focuses on controlling seizures, although drug resistance can occur. Infants and newborns typically require a multidisciplinary approach involving neurologists, metabolic specialists, and other healthcare professionals to manage their symptoms and provide comprehensive care.

Suggested MER for Evaluation:

• •

  Clinical examination;

• •

  Genetic testing;

• •

  Imaging studies; and

• •

  Laboratory test results.

Suggested Listings for Evaluation:

111.02

112.02

112.05

112.10

112.11

112.14