Sex Chromosome Disorders Test 2 Flashcards
Turner Syndrome
Pathophysiology
45XO (gondal dysgenesis)
Turner Syndrome
Incidence
1: 2,500 female births, no correlation to advanced maternal age or paternal link
- most common chromosome cause of spontaneous abortions or miscarriage
Turner Syndrome physical features
- webbed neck
- cubital valgus
- dorsal edema of hands and feet
- hypertelorism (wide set eyes)
- epicanthal folds
- ptosis( dropping eyelids)
- elongated ears
- growth retardation
Turner Syndrome
other systems effected
- congenital heart disease( septal defects, heart valve issues)
- kidney malfunction
- hearing loss
- decreased gustatory and olfaction
- deficits in spatial perception and orientation ( problems w/ motor function)
- average intellect in most
- sexual infantilism-don’t develop secondary sex characteristics (breasts, infertile)
Turner Syndrome -skeletal abnormalities
- hip dislocation
- foot deformities
- osteoporosis-low estrogen levels-managed w/ meds
- idiopathic scoliosis- no known cause
Klinefelter syndrome
47XXY
- increased levels of estrogen
Incidence of Klinefelter syndrome
1:1,000
Clinical Pic of Klinefelter syndrome
- testes fail to enlarge
- gynecomastia (male breast development)
- normal IQ
- sterility
Klinefelter syndrome ( severe karotypes)
- severe MR
- microcephaly
- hypertelorism (wide set eyes)
- strabismus
- celft palate
- radioulnar stenosis (limitations in pronation and supination
- genu valgus
- malformed cervical vertebrae( alignment /posture issue)
- pes planus
Fragile X disease pathophysiology
structural abnormality of the X chromosome
- in females the 2nd X can compensate for abnormaility
Fragile X disease incidence
1:1,200 carried on in males
Clinical features of Fragile X disease
- large head/ears/jaw
- myopia (hard to see far away)
- V-shaped palate
- large testes
- active/autistic ( hyperactive
- not any major health issues -may be on track with motor development
Partial Deletion of chromosome
- a section of a chromosome is missing
- often has be been deleted in the replication process during meiosis (gametogenesis)
- named by chromsosome # and location of deletion on the long or short arm (Q-long, P-short)
- deletion may be on any autosome
Partial deletion Syndromes
- Wolf-Hisrchhorn syndrome
- Cri-du-Chat Syndrome
- Prader Willi Syndrome
Wolf-Hisrchhorn syndrome pathophysiology
- partial deletion syndrome
- 46XY-4P or 46XX-4P
Wolf-Hisrchhorn syndrome prevalance
120 cases as of 1992, 2010 ~500 individuals in US
Clinical features of Wolf-Hisrchhorn syndrome
-severe psychomotor and growth retardation
-hypertonicity
- seizures
-microcephaly
-hypertelorism
-cleft lip/palate
-heart malformation
-hip dislocation
-club feet ( PF, supination, Inversion)
(physical and cognitive features)
Cry-du-Chat syndrome pathophysiology
- partial deletion syndrome
- 46XY-5p or 46XX-5p
Incidence of Cry-du-Chat syndrome
1:20,000
Clinical features of Cry-du-Chat syndrome
-high pitched cat like cry
-microcephaly
-intrauterine growth retardation
-hyperteleorism
-strabismus
-low set ears
-severe MR
- tone abnormalities ( typically increased)
-scoliosis
-hip dislocation
-club feet
-mid-line hair (synapharies)
-hyper-extensible fingers/toes ( increased lig. laxity)
respiratory and feeding problems
(typically very involved indiv. -PT works with positioning for breathing and feeding)
Prader Willi Syndrome pathophysiology
-partial deletion syndrome
46XY-15q or 46XX-15q
Incidence of Prader Willi Syndrome
1:10,000
Early Clinical features of Prader Willi Syndrome
- hypotonia,
-expressionless face
-weak cry
-poor feeding
-slow weight gain
-dysmorphic facial features
( may have dx of FTT, uninterested in environment, oral motor issues
typically able to but delayed motor skills; walking running etc
may have cognitive issues throughout life)
Late Clinical features of Prader Willi Syndrome
- improved mm tone w/ coordination and motor delays
- persistent/ compulsive appetite ( hyperphagia- overactive eating (food & nonfood substances))
- obesity
- hypogonadism (don’t develop sexually- male or female)
- mild/moderate MR
- maladapive behaviors( self-injury( head banging, picking, biting)
PT for Prader Willi Syndrome
early- assit w/ eating
late - physical act. to limit obesity
Autosomal Dominant disorders
results from an abnormality or mutation in a single gene
-abnormal or mutated gene overrides the normal allele inherited from the other parent
Osteogenesis Imperfecta phyophysiology
autosomal dominant disorders
deficits in collagen synthesis
-4 types
-different in tissue that are more or less involved
-typically type 4 is the most severe (only 25% of normal collagen is produced)
Osteogenesis Imperfecta incidence
1:20-30,000
Clinical picture of Osteogenesis Imperfecta
types I-IV,
-brittle bone
- hyperextensible lig (dislocations due to laxity)
-blue teeth
-blue sclera in eyes
-skeletal deformities
-small statue
-deafness
- small limbs
-respiratory prob (poor rib mobility, fx, harder to clear secretions)
(may have fx in utero bc tight space or during vaginal birth- C-section with prior knowledge)
Management of Osteogenesis Imperfecta
- proper positioning of feeding /changing
- may lve normal lifew/ major skeletal deformities
- most non-ambulatory( trauma –> fx or hip dislocation)
- just picking them up could lead to fx- pain mgmt
autosomal dominant disorders
- Osteogenesis Imperfecta
- Tuberous Sclerosis
- Neurofibromatsis ( von Recklinghausen disease)
- Huntingtons Chorea
- Charcot-Marie-Tooth Disease
Tuberous Sclerosis pathophysiology
autosomal dominant disease
spontaneous mutation related to increased paternal age
Tuberous Sclerosis incidence
1:10,000
clinical pic of Tuberous Sclerosis
triad of symptoms
-seizures ( result of brain tissue tumor-typically astrocytes)
-MR
-sebaceous adenoma- sebaceous gland tumor or growth
(kidneys may be involved)
mgmt of-Tuberous Sclerosis
depending on size of tumor- may be able to remove if causing seizure
-txt for hydrocephalus
Neurofibromatsis ( von Recklinghausen disease) pathophysiology
autosomal dominant disease
- spontaneous mutation or family related
Neurofibromatsis ( von Recklinghausen disease) incidence
1:3,500
Clinical pic of Neurofibromatsis ( von Recklinghausen disease)
-cafe au lait spots,
-neuromfibroma ( growths on nerves -PNS/CNS-pain & disruption of function
-MR
-seizures
(motor/sensory/autonomic issues)
-may be painful/disfiguring, fatal or decreased life expectancy depending on location
mgmt of Neurofibromatsis ( von Recklinghausen disease)
go in and remove fibromas ( depends on location)
Huntington’s Chorea pathophsiology
gross atrophy of corpus striatum, neuronal degeneration caudate nucleus/ putamen/ deep nuclei, and frontal cortex
Huntington’s Chorea Incidence
6.5:100,000
clinical pic of Huntington’s Chorea
-choreic mvmts
-variable presentation / progression
(cognitive and motor issues)
-typical onset ~40 y/o (may not know before reproduce)
Huntington’s Chorea Mgmt
meds for choreic mvmts ( may have sedation effect)
Charcot-Marie-Tooth Disease pathophysiology
also known as heredity motor and sensory neuropathy or peroneal muscular atrophy (HMSN)
incidence of Charcot-Marie-Tooth Disease
1:2,500 births
- CMT-1
-CMT-2
-CMT-3
-CMT-4
-CMT X
differ in severity and function
clinical pic of Charcot-Marie-Tooth Disease
-significant weakness of foot/ leg
-pes cavus, foot drop, hammer toe
-may affect UE/hands
- motor and sensory loss~pain
-CMT-2 later stages :mm wasting/ atrophy in leg & foot
(inverted champagne botttle- hallux valgus& varus)
Charcot-Marie-Tooth Disease DX
w/ karyotype
Charcot-Marie-Tooth Disease Mgmt
strength & maintain ROM
-use orthoses to improve &maintain function and deformity
Autosomal Recessive
the allele is inherited from each parent is abnormal
- combination of two alleles results in disease state
- parents do not typically have the specific disease
Autosomal Recessive
- hurler syndrome
- Phenylketonuria (PKU)
- sickle cell anemia
- Cystic Fibrosis
- Wilson’s disease ( Hepatolenticular Degeneration)
- Fredreich’s Ataxia (Hereditary Spinocerebellar Ataxia)
- Krabbe’s Disease (Globoid Leukodystrophy, Galactosylceramide)
- Tay Sachs
Hurler’s Syndrome pathophysiology
aka: gargoylism & mucopolysacaridosis
- error in metabolism of polysaccrides- severely impacts other body systems
Hurler’s Syndrome Incidence
1:100,000
Hurler’s Syndrome Clinical picture
appear normal at birth with symptoms progressing over 1-3 y/o
- facial deformity
- progressive mental & physical deterioration
- early death 2ndary to cardiac pathology
Pheylketonuria pathophhysiology
-absence of phenylalanine hydroxylase prevents conversion of phenylanlaine to tyrosine ( increased phenylalanine–> CNS defects
Pheylketonuria Incidence
1:10-15,000, northern european ancestery
Pheylketonuria clinical pic
- untreated causes Mental / growth retardation
- seizures
- movement disorders
Pheylketonuria Mgmt
- manage w/ diet; no diet pop, carbs (bread/ cereal)
- caught early may have little to no CNS damage
- caught late- severe CNS disorder
- ongoing throughout life
Sickle Cell Anemia pathophysiology
- recessive autosomal
- chronic hemolytic anemia
-sickle shaped RBCs - inheritance of HbS
(increased likelihood of coagulation–> clot-> stroke
diminishes O2 carrying capacity)
Sickle Cell Anemia Incidence
almost exclusively afroamericans
Sickle Cell Anemia Clinical Pic
- related to anemia and thrombosis/infarction
- severe anemia
- jaundice (body cant break down RBC to decrease bilirubin -> jaundice)
- arthralgia
- aseptic necrosis from femoral head (blood supply cut off due to blockage or disruption)
- hemiplegia ( stroke in brain)
- cranial nerve palsies( disruption of blood to CN or CN nuclei)
- pulmonary and renal hemiplegia
Sickle Cell Anemia Mgmt
blood transfusions
Cystic Fibrosis pathophysiology
-effects exocrine ( excretes to outside environment) glands and sweat glands
Cystic Fibrosis Incidence
1:2,000white, 1:17,000 afroamericans, rare in asians
Clinical pic of Cystic Fibrosis
affects digestive and respiratory systems( enzymes not produced or in an ineffective form)
-decreases lifespan~20-30y/o ( increased risk of respiratory infection
Wilison’s Disease
aka Hepatolenticular degeneration
Wilison’s Disease pathophysiology
abnormality of copper metabolism/ accumulation of copper within body tissues
-onset 12-20 y/o (takes awhile to build up)
- unknown incidence
(metal in body is harmful multiple systems ; CNS, ie lead CNS porb~develop mental issues in children
intentional tremor- tremor w/ mvmt)
Wilison’s Disease incidence
unknown
Wilison’s Disease clinical pic
- intention> resting tremors
- choreoathetoid mvmts
- rigidity
- dysartrhia ( trouble speaking)
- dementia
- cirrhosis( toxic to liver, decreased function)
- Kayser-Fleischer ring(orange copper colored ring around eye)
Wilison’s Disease Mgmt
- medication to help clear levels of copper
- can’t reverse damage but prevent worsening
- manage levels
Fredreich’s Ataxia ( Heredity Spinocerebellar Ataxia) pathophysiology
-degeneration of posterior spinal root( sensory issues ), posterior spinal cord( cordination/ balancing issues/sequencing timing prob.), cerebellum, dorsal and ventral degeneration of spinocerebellar tracts and lateral corticospinal tracts
Fredreich’s Ataxia ( Heredity Spinocerebellar Ataxia) Incidence
1-2:100,000
Fredreich’s Ataxia ( Heredity Spinocerebellar Ataxia) Clinical Picture
- ataxic gait
- dysmetria of UE/LE ( issue w/ timing and accuracy of reach;reach past object-hypermetria, reach for object &fall short-hypometria)
- speech disturbances
- pes cavus
- cardiomyopathies
- disrthmia?- trouble w/ tongue and breathing sequencing problems
Fredreich’s Ataxia ( Heredity Spinocerebellar Ataxia) Mgmt
- supportive
- gait
Krabbe’s Disease (Globoid Leukodystrophy, Galactosylceramide) pathophysiology
deficiency of gaslactocerebroside B-galactosidase
Krabbe’s Disease (Globoid Leukodystrophy, Galactosylceramide) Incidence
1:100,000-200,000
Krabbe’s Disease (Globoid Leukodystrophy, Galactosylceramide) Clinical Picture
-may appear normal at birth
-progressive retardation
-paralysis
-blindness
-deafness
-pseudobulbar palsy
-fatal generally within 2 years
(may have CP presentation, effects CN, may live to be older- hunter kelly 7ish )
Krabbe’s Disease (Globoid Leukodystrophy, Galactosylceramide) Mgmt
- supportive
- rare
- don’t typically have successful txt ( hard to deliver, blood brain barrier)
- identification is hard
Tay Sachs Pathophysiology
genetic mutation on chromosomes 15q
- inability to produce hexosaminidase
- CNS degenation
Tay Sachs Clinical Picture
- decline in infant ( early death, develop in utero-see by 3-6mo, die by 4-5 y/o, juvenile~less common)
- blind/ deaf
- decreased eye contact
- decreased strength
- decreased life expectancy (death at a young age)
- delay or decline in motor control
- seizures
- dementia
Tay Sachs Prevalence
-more prevalence in Ashkenazi jewish community bc they all marry each other (high as 1/27 births)
Tay Sachs Mgmt
-supportive
X-linked Recessive Inheritance
-also called sex linked inheritance
-only males affected
- females are carriers
-family history: normal females and affected males
(females extra X chromosome~ may see some characteristic w/ disease process but don’t have disease)
Sex linked inherited disorders
- Lowe’s syndrome ( Oculocerebrorenal)
- Lesch-Nyhan Syndrome ( Heredity Choreathetosis)
- Hemophilias
- Muscular dystrophy
-Lowe’s syndrome ( Oculocerebrorenal) pathophysiology
- sex linked disorder
- metabolic acidosis develops by 6 mo
Lowe’s syndrome ( Oculocerebrorenal) Incidence
rare, all male
Lowe’s syndrome ( Oculocerebrorenal) Clinical Pic
-progressive MR
-renal dysfunction (inability to balance)
- cortical cataracts( center of eye(
-glaucoma ( build-up of pressure in eyes)
-demyelination
-gliosis(reaction of glia cells to damage, compensate for damage~proliferation of astrocytes&olgiodentrites)
-hypotonicity
-growth retardation
- failure to thrive
-piercing cry
-death 2ndary to renal failure
( eyes/kidneys/CNS affected, may not be evident at birth by 6 mo begin to develop signs/symptoms, decline in cognitive function)
Lowe’s syndrome ( Oculocerebrorenal) Mgmt
-supportive
Lesch-Nyhan Syndrome ( Heredity Choreathetosis) pathophysiology
overproduction of uric acid causing deficiency in hypoxanthine-guaninephospho-robosyltransferase (HGPRT) in brain, liver and amniotic cells
- issues in brain, liver & amniotic cells as developing
- difficulty swallowing /speaking
Lesch-Nyhan Syndrome ( Heredity Choreathetosis) Incidence
1:10,000 males
Lesch-Nyhan Syndrome ( Heredity Choreathetosis) Clinical Picture
- appear normal at birth
- at 1-2 y/o begin self mutilation
- normal pain perception
- progressive spastic paresis/plegia by 1 y/o
- chorea
- tremor
- growth retardation
- dysarthria
- dyspahgia
- MR
- skeletal deformity (bony deformity, contractures, scoliosis)
Lesch-Nyhan Syndrome ( Heredity Choreathetosis) Mgmt
meds to manage levels of uric acid
Hemophilias pathophysiology
bleeding disorders due to inherited deficiencies or abnormalities of coagulation factors
- inability to clot
- or increased brusing to less force
- minor injury could be life threatening
Hemophilias Incidence
1:10,000 males (female transmit abnormal gene)
Hemophilias Clinical features
- hemarthrosis( blood in joint, painful/inflamed/ degeneration of joint over time)
- hemotoma
- hemauria
- hemorrhages from minor injuries
Muscular Dystophy
-sex linked disorder
Types
-Duchenne’s MD (pseudohypertrophic MD, Progressive MD [at mm level])
-X-linked
-Becker’s X-linked
-Congenital Autosomal Recessive
-Congenital Myotonic Autosomal Dominant
-Childhood Onset Facioscapulohumeral (affects proximal UE)
-Emery-Dreifus
-Spinal muscular atrophy ( ant horn cells)
( all slightly different clinical pictures/time onset/challenges/severity of impairments)
Pathophysiology of Muscular Dystrophy- Duschenne’s
-mutation of dytropha?
(protein on the level of the sarcomere that helps to rebuild mm when stressed or damaged)
-mm strain/stress leads to damage -not able to be repaired- mm tissue is replaced w/ connective tissue and fat: pseuohypertrophy)
-mm less effective at generating force
-affects all skeletal mm
-leads to death (bc involves diaphragm-respiratory death)
-less able to clear secretions, increased risk of iinfection
Muscular Dystrophy- Duschenne’s Incidence
20-30/100,000 live births, males only
Muscular Dystrophy- Duschenne’s : Grower’s Sign
characteristic way of getting off the floor
-apparent issue by 2 y/o, child is becoming weaker
-child attempts to get off floor using UE for help
( floor-> bear walk postion-> walk up legs to get into standing, due to decreased hip/knee ext.)
Muscular Dystrophy- Duschenne’s Clinical Picture
–apparent weakness at 2 y/o
-unable to walk by 9-10 y/o
-clumsy, fall down
-waddling gait w/trendelemburg
-trouble w/ standing
-weakness occurs proximal -> distal * hips/shldrs
-psuedohypertrophied gastrocs
-hip flexor contracture
-increased lumbar extension
-hang out on lig.
use wheelchair~typically not self propelled (power WC) bc increased damage to mm
-linked to scoliosis-when no longer can walk
-may use stander walker or tilt table to decrease risk of scoliosis
-may result in restrictive lung disease bc of atrophy in diaphragm and rib mm
Muscular Dystrophy- Duschenne’s Mgmt
- manage symptoms
- typically only live into early 20s
- often trached to help breathe and clear secretions
- ventilators can be attached to WC
Dx of Muscular Dystrophy- Duschenne’s
- mm biopsy (punch biopsy)
- genetic testing
- mm EMG
- look at serum enzymes (CPK- increased levels in blood with damage to mm)
- use U.S. to examine heart
Spinal Muscular Atrophy pathophysiology
-type of muscular dystrophy
-disease in ant horn cells
-accelerated rate of neuronal cell apoptosis
(damage at mm level or lack of innervation -> mm damage, both have increased CPK)
-4 types
Spinal Muscular Atrophy Incidence
1/6,000
-more common in males and more severe in males
Dx of Spinal Muscular Atrophy
- serum enzymes (CPK
- EMG
- mm biopsy
Types of Spinal Muscular Atrophy
4
Type I of Spinal Muscular Atrophy
- more severe
- affects younger infants( birth to first few mo)
- decreased life expectancy
Type II of Spinal Muscular Atrophy
- onset 6-12 mo
- live awhile , progresses slower
Type III of Spinal Muscular Atrophy
-early childhood 3-5 to adolescence
Type IV of Spinal Muscular Atrophy
- after 30 y/o
- maintain higher level of function
- weak, develop contractures
- use of mobility based ADs
- decreases life expectancy
Multifactorial disorders
- combination of genetic and environmental factors are thought to create certain birth defects
- cleft palate
- Spinia Bifida (myelomeningocele)
- heart disease
- diabetes
Cleft Palate
environmental and genetic predispostion
- unable to breathe /suck/ swallow
- cannot close mouth around bottle or nipple
- can fix within few mo of life or wait if medically unstable or cleft closed-only lip affected
- can have w/out other disease processes
Spinia Bifida (myelomeningocele)
folic acid deficiency
-genetic predisposition
Diabetes
type I -genetic predispostion or environmental virus-> autosomal effect
Cornelia DeLang Syndrome pathophysiology
unknown, Mediterranean background
-possible genetic link & environmental factors
Cornelia DeLang Syndrome Incidence
unknown, several cases in western NY
CLinical Presentation of Cornelia DeLang Syndrome
-hairy
-synapheries
-severe MR
-congenitally malformed limbs
-very small statue (limbs& trunk)
(may have absence of bone or shortened and unable to function)
Cornelia DeLang Syndrome Mgmt
supportive
Torsion Dystonia pathophysiology
genetically linked progressive disorder
Torsion Dystonia Incidence
rare
Torsion Dystonia Clinical Picture
-gradual onset of slow spasmodic, twisting mvmts causing dystonia
(challenging to develop and maintain function)
