Spinal Muscular Atrophy

Overview

Definition

Spinal muscular atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation (SMA) is a spectrum of autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance syndromes characterized by progressive proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome and atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation, possibly due to degeneration of the anterior horn Anterior horn One of three central columns of the spinal cord. It is composed of gray matter spinal laminae VIII and ix. Brown-Séquard Syndrome cells in the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy and motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology nuclei in the lower brainstem.

Classification

• Type 0: prenatal-onset SMA
  • Presence of only 1 copy of the survival motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron 2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (SMN2) 
  • Decreased fetal movement in late pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Manifests with severe, flaccid paralysis
• Type 1: infantile SMA, also called Werdnig-Hoffman disease
  • Onset before 6 months of age
  • Never able to sit up independently
• Type 2: intermediate form, also called Dubowitz disease
  • 20% of cases
  • Onset between 3 and 15 months of age
  • Unable to stand or walk independently
• Type 3: juvenile form, also called Kugelberg-Welander disease
  • 30% of cases
  • Onset between 18 months and 18 years of age
  • Normal lifespan
• Type 4: adult SMA (mildest form)
  • < 5% of cases
  • Presence of 4–8 copies of SMN2
  • Able to maintain ambulation throughout life
  • Normal lifespan

Epidemiology

• 2nd-most common autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder (after cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans), causing significant morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: calculated to be 1 in 11,000 in the US among all ethnicities
• Carrier Carrier Vaccination frequency: 1 in 47 Caucasians and 1 in 72 African American individuals

Pathophysiology

• Homozygous deletion of the survival motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron 1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (SMN1) → loss of synthesis Synthesis Polymerase Chain Reaction (PCR) of survival motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron protein
• Extra copies of SMN2 determine the phenotypic expression/clinical severity.
• Dysfunctional SMN protein → anterior horn Anterior horn One of three central columns of the spinal cord. It is composed of gray matter spinal laminae VIII and ix. Brown-Séquard Syndrome cells in the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy and motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology nuclei in the lower brainstem undergo degeneration → progressive muscle weakness
• Mechanisms by which the lack of normal SMN protein causes SMA pathology are unclear.
• Pathophysiology in a mouse model (2014) shows skeletal muscle damage preceding motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neuron damage.

Clinical Presentation

Spinal muscular atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation presents as a lower motor neuron Lower Motor Neuron Motor Neuron Lesions lesion syndrome with muscle weakness, which is more severe in types 0, 1, and 2.

Type 0: decreased fetal movement in late pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

• Documented polyhydramnios Polyhydramnios Polyhydramnios is a pathological excess of amniotic fluid. Common causes of polyhydramnios include fetal anomalies, gestational diabetes, multiple gestations, and congenital infections. Patients are often asymptomatic but may present with dyspnea, extremity swelling, or abdominal distention. Polyhydramnios, fetal growth restriction Fetal growth restriction Fetal growth restriction (FGR), also known as intrauterine fetal growth restriction (IUGR), is an estimated fetal weight (EFW) or abdominal circumference < 10th percentile for gestational age. The term small for gestational age (SGA) is sometimes erroneously used interchangeably with FGR. Fetal Growth Restriction, and pulmonary hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS)
• After birth:
  • Severe hypotonia Hypotonia Duchenne Muscular Dystrophy and weakness
  • Areflexia Areflexia Duchenne Muscular Dystrophy
  • Facial diplegia (paralysis on both sides)
  • Arthrogryposis (multiple joint contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing)
  • Congenital Congenital Chorioretinitis heart defects
  • No motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology milestones are achieved.

Type 1: presents before age 6 months of age

• Severe and symmetric flaccid paralysis
• Infants do not achieve the ability to sit without support.
• “Frog-like” posture with hips abducted
• Bulbar weakness:
  • Weak cry
  • Poor sucking and swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility reflexes
  • Pooling of secretions
  • Tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy fasciculations Fasciculations Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations may be visualized as a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of motor neuron disease or peripheral nervous system diseases. Polyneuropathy
  • Increased risk of aspiration and FTT FTT Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive
• Progressive respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
• Bell-shaped chest
• Cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. The 12 Cranial Nerves: Overview and Functions are spared:
  • Preserved eye movement
  • Normal expression/ facial muscles Facial muscles The facial muscles (also called mimetic muscles) control facial expression and are supplied by the facial nerve. Most of them originate from the skull and attach to the skin around the facial openings, which serve as a method to group or classify them. Facial Muscles: Anatomy

Type 2: presents at 3–15 months of age

• Progressive proximal weakness in legs > arms:
  • The ability to sit independently is delayed and then lost in teenage years.
  • Inability to stand or walk
• Sparing of the face and eye muscles
• Tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy fasciculations Fasciculations Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations may be visualized as a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of motor neuron disease or peripheral nervous system diseases. Polyneuropathy
• Areflexia Areflexia Duchenne Muscular Dystrophy
• Muscular weakness → progressive scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
• Small amplitude myoclonic tremor-like movements of the hands (polyminimyoclonus) 
• Ankylosis of the mandible Mandible The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. Jaw and Temporomandibular Joint: Anatomy
• Joint contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
• Respiratory muscle weakness Respiratory muscle weakness Respiratory Acidosis and scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis from progressive muscular weakness → restrictive lung disease

Type 3: presents from 18 months of age to the end of adolescence

• Achieve independent ambulation → later presents with progressive proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome in legs > arms
  • Falls
  • Difficulty climbing stairs
• May develop foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy deformities
• Most individuals do not develop scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis or respiratory muscle weakness Respiratory muscle weakness Respiratory Acidosis.
• Many individuals become wheelchair-bound as the disease progresses.

Type 4 (mildest phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics): presents in adulthood

• Mild proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome (lower extremities)
• Ambulation is usually maintained.

Diagnosis

Spinal muscular atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation should be suspected in any infant with unexplained weakness or hypotonia Hypotonia Duchenne Muscular Dystrophy. Definitive diagnosis requires genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies.

Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies

• Gold standard
• Targeted mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations analysis to confirm SMN1 deletion
• For parents of an affected child: autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance mode of inheritance →
  • 25% chance of an affected child
  • 50% chance of a carrier Carrier Vaccination
  • 25% chance of an unaffected child
• Slight deviation with SMA:
  • 2% of affected individuals have a de novo SMN1 variant with only 1 parent being a carrier Carrier Vaccination of that variant →
  • Siblings are not at increased risk for SMA.
• Carrier Carrier Vaccination testing is indicated for at-risk relatives.
• Prenatal testing is indicated for women having a family member with a confirmed diagnosis of SMA (by genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies).
• Newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screening Screening Preoperative Care was added to the Recommended Uniform Screening Screening Preoperative Care Panel (RUSP) in 2018, and SMA screening Screening Preoperative Care is being conducted in many states.
  • The RUSP consists of a list of disorders recommended by the US Department of Health and Human Services for newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screening Screening Preoperative Care in the state.
  • Only tests for SMA due to homozygous deletion of exon 7 in SMN1

Electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy (EMG) and muscle biopsy Muscle Biopsy Trichinella/Trichinellosis

• Formerly, a standard component of diagnostic evaluation
• Rarely used now because of the availability of molecular genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies

Management

Current management is mostly supportive and multidisciplinary (including palliative care).

Supportive care

• Respiratory support:
  • Noninvasive: BiPAP BiPAP Noninvasive Ventilation
  • Invasive:
    • Tracheostomy Tracheostomy Surgical formation of an opening into the trachea through the neck, or the opening so created. Laryngomalacia and Tracheomalacia/ ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing
    • Considered when noninvasive ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing is insufficient
  • Chest physiotherapy Physiotherapy Spinal Stenosis for secretion Secretion Coagulation Studies mobilization and clearance
  • Tracking of forced vital capacity Vital capacity The volume of air that is exhaled by a maximal expiration following a maximal inspiration. Ventilation: Mechanics of Breathing
• Nutritional support:
  • Early gastrostomy for growth failure Growth failure Chronic Granulomatous Disease in types 1 and 2
  • Supplemented nutrition reduces the likelihood of aspiration.
• Orthopedic support:
  • Physical therapy Physical Therapy Becker Muscular Dystrophy
  • Spinal bracing for scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis

Disease-modifying therapy

Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics therapy: 3 agents are now available in the US.

• Nusinersen (Spinraza): antisense oligonucleotide that increases SMN protein synthesis Synthesis Polymerase Chain Reaction (PCR)
  • Administered by intrathecal injection
  • Direct comparisons with other agents are not yet available.
• Onasemnogene abeparvovec (Zolgensma):
  • 1-time IV infusion for children < 2 years of age
  • Recombinant viral vector containing complementary DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure that encodes normal human SMN protein
• Risdiplam (Evrysdi):
  • Oral medication for all types of SMA in individuals > 2 months
  • Corrects SMN2 splicing errors and increases the concentration of SMN protein

Complications

• Failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive ( FTT FTT Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive) in infants:
  • Bulbar dysfunction affects swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility.
  • → Growth failure Growth failure Chronic Granulomatous Disease due to inadequate caloric intake Inadequate Caloric Intake Failure to Thrive
• Respiratory complications:
  • Aspiration
  • Mucus plugging
  • Recurrent infections Recurrent infections Common Variable Immunodeficiency (CVID)
  • Restrictive lung disease
• GI complications:
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Delayed gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility
  • Gastroesophageal reflux with potential aspiration
• Musculoskeletal complications:
  • Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
  • Joint contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
  • Hip subluxation Subluxation Radial Head Subluxation (Nursemaid’s Elbow)
  • Susceptibility to fractures
• Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep difficulties

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Types 0, 1, and 2: death due to restrictive respiratory disease and respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
  • Type 0: death at birth or in the 1st month of life
  • Type 1: death at < 2 years of age
  • Type 2: Life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids is variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables and ⅔ of individuals live up to 25 years of age.
• Type 3: slowly progressive worsening of motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology weakness, but individuals have a normal lifespan
• Type 4: normal lifespan

Differential Diagnosis

• Prader-Willi syndrome Prader-Willi syndrome Prader-Willi syndrome (PWS) is a rare autosomal neurodevelopmental genetic disorders mapped to a specific region of chromosome 15 attributed to genomic imprinting. A paternally derived chromosome 15 with this deletion results in 15q11-13 paternal deletion syndrome, or PWS. Prader-Willi Syndrome and Angelman Syndrome: a condition associated with the loss of the paternal chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 15q11-13 region, which manifests as intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment, short stature, underdevelopment of sexual organs, and obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity in newborns. At birth, Prader-Willi syndrome Prader-Willi syndrome Prader-Willi syndrome (PWS) is a rare autosomal neurodevelopmental genetic disorders mapped to a specific region of chromosome 15 attributed to genomic imprinting. A paternally derived chromosome 15 with this deletion results in 15q11-13 paternal deletion syndrome, or PWS. Prader-Willi Syndrome and Angelman Syndrome presents with hypotonia Hypotonia Duchenne Muscular Dystrophy and lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, and feeding and breathing difficulties similar to those in SMA. Diagnosis is made based on DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids testing to detect parent-specific imprinting Imprinting The variable phenotypic expression of a gene depending on whether it is of paternal or maternal origin, which is a function of the DNA methylation pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. Epigenetic Regulation of specific regions of chromosome 15 Chromosome 15 Marfan Syndrome. Management is supportive.
• Duchenne muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy: an X-linked recessive X-Linked Recessive Duchenne Muscular Dystrophy genetic disorder in children caused by a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the DMD DMD Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder that is caused by a mutation in the dmd gene. The mutation leads to the production of abnormal dystrophin, resulting in muscle-fiber destruction and replacement with fatty or fibrous tissue. Duchenne Muscular Dystrophy gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics, leading to muscle-fiber destruction and replacement with fatty or fibrous Fibrous Fibrocystic Change tissue. Affected boys present with progressive proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome that eventually leads to loss of ambulation, and contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing, scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis, cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types, and respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure. Diagnosis is based on laboratory and genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management is supportive and aimed at slowing disease progression and complications.
• ALS ALS Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a sporadic or inherited neurodegenerative disease of upper motor neurons (UMNs) and lower motor neurons (LMNs). ALS is the most common progressive motor neuron disease in North America, primarily affecting men and individuals of Caucasian ethnicity. Amyotrophic Lateral Sclerosis ( Lou Gehrig’s disease Lou Gehrig’s disease Amyotrophic lateral sclerosis (ALSs), also known as Lou Gehrig’s disease, is a sporadic or inherited neurodegenerative disease of upper motor neurons (UMNs) and lower motor neurons (LMNs). Als is the most common progressive motor neuron disease in North America, primarily affecting men and individuals of caucasian ethnicity. Amyotrophic Lateral Sclerosis): a sporadic Sporadic Selective IgA Deficiency or inherited neurodegenerative disease in adults that affects the upper motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology (UMNs) and lower motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology (LMNs). Amyotrophic lateral sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor is characterized by symptoms indicating that both the UMNs and LMNs are affected concurrently. The diagnosis is made clinically. Management is supportive and symptomatic, progressing to end-of-life care.