Genetic & Developmental Disorders Part 1 PDF

GENETIC & DEVELOPMENTAL DISORDERS PTA 104: FUNDAMENTALS OF DISEASE  COURSE OBJECTIVES 4. List and describe common diagnostic studies and tests used to diagnose and monitor diseases. 5. Discuss the use of pharmacological agents in the treatment of disease and...

GENETIC & DEVELOPMENTAL DISORDERS PTA 104: FUNDAMENTALS OF DISEASE  COURSE OBJECTIVES 4. List and describe common diagnostic studies and tests used to diagnose and monitor diseases. 5. Discuss the use of pharmacological agents in the treatment of disease and associated implications for physical therapy. 6. List and describe major disorders and diseases caused by inherited genetic code defects. BUT FIRST, A LITTLE BACKGROUND INFORMATION… https://www.youtube.com/watch?v=hywRdDVR76A  DNA, GENES, AND DNA = composed of different combinations of ALLELES molecules called nucleic acids Sequence of nucleic acids provides instructions for assembling amino acids, which are the basic structural units of proteins Genes = chemical messengers of heredity 30,000 human genes Passed from parent to offspring Change in normal DNA pattern of particular gene = mutation Allele = variant of a gene Dominant or recessive  DOMINANT VS RECESSIVE ALLELE Dominant Recessive Characteristic it is Characteristic it is connected to will be connected to is less likely expressed in an individual to be expressed Can mask the Only manifest when presence of a both alleles are recessive gene recessive in an individual  FATHER MOTHER (CARRIER) (CARRIER) Dominant expression Dominant Recessive (Carriers) 25% 50% 25%  GENOTYPE AND PHENOTYPE Genotype: Individual’s collection of genes, genetic makeup or allele combination Refers to the two alleles inherited for a particular gene (one from each parent) Homozygous = same alleles Heterozygous = different alleles Phenotype = the expression of the genotype contributes to the individual's observable traits, called the phenotype  CHROMOSOME DNA storage unit Human DNA organized into 2 sets of 23 chromosomes 22 pairs of autosomes carry matched information 1 pair of sex chromosomes Males have XY, females have XX sex chromosomes (#23) A male child receives the X chromosome from the female parent & a Y chromosome from the male parent A female child receives an X chromosome from each parent  BASIC TERMINOLOGY Congenital – present at birth, inherited, genetic or developmental defects due to damage in utero Genetic – consequence of gene changes to the 23 chromosomes in each cell Chromosomal – abnormal or dislocation of chromosomes Developmental – damage to body structures during development or shortly after birth Multi-factorial – combo of genetic predisposition and exposure  DIAGNOSTIC TESTS Bone scan – injection of radionuclide into the body; body scanned with a gamma camera to see which bones have taken up radioactive material; shows areas of high bone remodeling Electromyography (EMG) – recording of electric activity of a muscle/muscle group Nerve Conduction Velocity Test (NCV) – used to determine extent of nerve damage by measuring speed of electrical impulse through the nerve Muscle biopsy – removal of sample of tissue for study Magnetic Resonance Imaging (MRI) – uses magnetic fields and radio waves to produce cross sectional images of the body Useful for imaging soft tissues (muscles/tendons, ligaments, discs) X-ray – commonly used to diagnose issues with bone (fractures, dislocations, arthritis, bone infections) CHROMOSOMAL DISEASES  DOWN SYNDROME Trisomy 21 (extra chromosome) Occurs due to faulty cell division, which results in 47 chromosomes Advanced maternal age (>35 y/o) increases risk Characterized by muscle hypotonia, cognitive delay, abnormal facial features Alzheimer’s disease more common and occurs at an earlier age Symptoms seen in almost all people with Down syndrome by age 40  DOWN SYNDROME - PRESENTATION Alzheimer’s is more Muscle hypotonia common Intellectual disability Joint hypermobility Atlantoaxial instability of Flattened nasal bridge the cervical spine Almond eye shape – Subluxation between epicanthal folds C1 and C2 Shorter limbs Overall reduction in brain Small mouth weight Flat occiput Delayed motor development Congenital heart Flat feet disease Slower postural reactions Scoliosis Visual and hearing loss Single palmar crease  DOWN SYNDROME – PT INTERVENTIONS What PT interventions would be beneficial for patients with Down Syndrome? General exercise and fitness – avoid inactivity/obesity Stability, strength, endurance Maximize function Teach optimal movement patterns during developmental activities Maximizing respiratory function (decreased muscle tone can impact respiratory expansion) Caregiver education Atlantoaxial Instability (AA) – don’t want to compress spinal cord = avoid excessive neck flexion/extension - gymnastics, diving, butterfly stroke, etc.)  DOWN SYNDROME – INTERVENTIONS Other: May require surgical intervention for cardiac abnormalities DS also associated with epilepsy, celiac disease, constipation, blood, dermatologic, and musculoskeletal disorders Prognosis: Shorter life expectancy Majority do reach age 55  DOWN SYNDROME https://www.youtube.com/watch?v=4JP1epzbZqc&t=2s https://www.youtube.com/watch?v=OeSUSECYnIQ  PRADER-WILLI SYNDROME RARE genetic disorder due to a partial deletion of chromosome 15 Signs and Symptoms: Short height, small hands, feet, and sex organs Hypotonia Obesity and constant desire for food (starts age 2-6) Decreased coordination Intellectual disability, behavioral symptoms PT treatment: Postural control Exercise and fitness Gross and fine motor skills training AUTOSOMAL DOMINANT DISEASE  TYPES OF AUTOSOMAL DOMINANT DISEASES Huntington’s Disease Osteogenesis Imperfecta Marfan Syndrome  HUNTINGTON’S DISEASE Autosomal Dominant = Everyone with the gene will have the disease 50% chance of inheriting the gene from a parent Progressive neurological disease Common symptoms include choreic movements, changes in personality, ataxic gait, speech disturbances, mental deterioration Symptoms typically start in middle age 35-55 15-20 year life span after clinical manifestation Genetic testing is available, but controversial  OSTEOGENESIS IMPERFECTA (AKA: BRITTLE BONE DISEASE) Etiology: can be either autosomal dominant or autosomal recessive; about 25% have no family history (spontaneous mutation) Equal likelihood boys and girls Genetic defect on genes responsible for type I collagen synthesis Type I collagen is found in extracellular matrix of bone, skin, and tendon – Major structural protein Four primary types with widely varying degrees of severity (type II most severe)  OSTEOGENESIS IMPERFECTA – TYPES Type I: mildest form; near normal growth and appearance Frequency of fractures usually cease after puberty Type II: most severe form; child usually dies in utero or in early childhood Significant fragility, multiple fractures with severe deformities, soft skull Type III: severe, but greater ossification of skull Significant growth retardation and limitations in functional mobility, progressive deformities, ongoing fractures, severe osteoporosis Type IV: milder; mild to moderate fragility and osteoporosis Some may improve after puberty; near normal life expectancy  OSTEOGENESIS IMPERFECTA – PRESENTATION Osteoporosis/pathological fractures Deformity/Bowing of long bones Thin skin; Blue sclerae (abnormally transparent) Weakness – delayed motor skills Deformed teeth Impaired cardiopulmonary function Mobility depends on type Short stature ○ Type I – ambulatory Joint hypermobility ○ Type II – life-threatening complications at, or shortly Hearing impairment after, birth Scoliosis, kyphosis ○ Type III – power mobility Normal cognition ○ Type IV – variable  OSTEOGENESIS IMPERFECTA - TREATMENT AND MANAGEMENT Fracture and deformity prevention - positioning, facilitate safe mvmt, braces Maximize functional mobility & Independence Education - careful handling Assisted ambulation/mobility (scooters, walker, w/c), encourage weight-bearing Swimming, walking Strengthening – avoid rotational force, avoid long lever arms Avoid passive stretching – risk of fx or joint subluxation Focus on AROM, positioning, fracture management, use of splints/braces, weight-bearing Wheelchair Rx and training Prognosis varies  OSTEOGENESIS IMPERFECTA https://www.youtube.com/watch?v=o4m7cSeft4g  MARFAN SYNDROME The coding for the formation of connective tissue is affected = connective tissue is less elastic and more fragile The messaging system to turn off growth in the long bones is turned off = the individual tends to be very tall, with long arms, legs, fingers, and toes Scoliosis and abnormal formations of the rib cage are also common Pectus carinatum Pectus excavatum  MARFAN’S SYNDROME The most serious effects - in the aorta Because of weak connective tissue in the walls of the aorta - prone to aneurysm and dissection (tear) These can be fatal occurrences and can happen without warning to a seemingly healthy individual Other problems: Pneumothorax (air b/w lung & chest wall) Detached retina or dislocated lens in the eye Mitral valve prolapse in the heart  MARFAN SYNDROME https://www.kennedykrieger.org/stories/potential-magazine/summer- 2020/awe-inspiring-determination-ellie-marfan-syndrome AUTOSOMAL RECESSIVE DISEASE  TYPES OF AUTOSOMAL RECESSIVE DISEASES Spinal Muscular Atrophy (SMA) Cystic Fibrosis Sickle Cell Anemia Phenylketonuria  SPINAL MUSCULAR ATROPHY (SMA) A group of genetic diseases that cause muscle weakness Neuromuscular disease characterized by progressive weakness and wasting of skeletal muscles Results from degeneration of anterior horn cells Typically more pronounced in proximal muscles - such as the shoulders, hips, and back 2nd most fatal autosomal recessive disorder (after cystic fibrosis) Involves mutation on 5th chromosome Signs/Symptoms: Progressive muscle weakness and atrophy, diminished or absent deep tendon reflexes, normal intelligence, intact sensation, end-stage respiratory compromise Symptoms typically start between 6 and 18 months  SPINAL MUSCULAR ATROPHY Diagnosis: ○ Suspected due to clinical presentation ○ Muscle biopsy and Electromyogram (EMG) Treatment: ○ Prevent pulmonary infections ○ Facilitate positioning, feeding, access to play, and mobility ○ Scoliosis (fusion often required) ○ Caregiver education ○ Use of AD and adapative equipment Prognosis – varies dependent on age of onset (3 types) Type 1 – death occurs before age 3 Type 2 – most are nonambulatory by age 12 (live to 20-40) Type 3 – can remain ambulatory, life expectancy not impacted  SPINAL MUSCULAR ATROPHY (SMA) Medical Treatment: No cure but new medications are being used (gene therapy) Physical Therapy: Positioning and facilitation of optimal function Assistive devices and adaptive equipment Contracture management/prevention Scoliosis management Facilitate independence with function and mobility Facilitate the highest level of function Improve or maintain joint ROM/contracture management and or prevention Improve or maintain endurance Improve or maintain balance  SMA https://www.youtube.com/watch?v=tNyL2vZfq2I https://www.youtube.com/watch?v=eSPWxB8lUrQ  CYSTIC FIBROSIS Most common genetic inherited disease in caucasian population in the US Disorder of ion transport in exocrine glands that affects hepatic, digestive, reproductive and respiratory systems Predisposes to chronic bacterial airway infections Almost all develop obstructive lung disease  progressive loss of pulmonary function Severity of disease strongly correlated with socioeconomic status and access to health care Defective gene and protein on chromosome 7  CF https://www.youtube.com/watch?v=3N8kyc7AqKU  SICKLE CELL ANEMIA Most prevalent in people of African, Mediterranean, and Middle Eastern descent Presence of abnormal form of hemoglobin Causes RBCs to change from biconcave disk shape to a crescent or sickle shape once oxygen is released  SICKLE CELL ANEMIA Symptoms: Fatigue – anemia Pain Ulcers – common on legs, painful Blood clots CVA Acute chest syndrome (lung-related complication where sickled cells cannot be re-oxygenated in the lungs and adhere together causing infarction)  PHENYLKETONURIA (PKU) Autosomal recessive; most common in caucasian populations Rare, inherited disorder, presents w/in a few months of birth disorder prevents the body from breaking down phenylalanine (an amino acid in plant and animal foods, such as meat, eggs, fish, and soy products) Causes phenylalanine to build up in the blood, which can be toxic to the brain MR, behavioral, and cognitive issues due to elevated serum phenylalanine Signs and symptoms: typically present within a few months of birth; if untreated, severe intellectual disability occurs; may experience gait disturbances, hyperactivity, psychoses, abnormal body odor, and display features that are lighter in color Treatment: dietary restriction of phenylalanine; adequate prevention avoids all manifestations of disease