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87 Cards in this Set
- Front
- Back
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neurofibromatoses |
composed of 3 disorders
neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis
ALL HAVE DEVELOPMENT OF NERVE SHEATH TUMORS IN COMMON |
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neurofibromatosis type 1 |
characterized by skin and bone abnormalities from tumors growing along the nerves |
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neurofibromatosis type 2 |
bilateral acoustic schwannomas on the 8th cranial nerve, meningiomas, and epedymomas |
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schwannomatosis |
schwannomas and chronic pain |
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neurofibromatosis type 1 |
most common and results in neuropsych deficits
neurocutaneous autosomally dominant genetic disorder, with Sx affecting the CNS and skin |
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neurofibromatosis type 1 DX criteria |
need 2 of the following: -six or more cafe-au-lait macules more than 5 mm in diameter in prepubertal individuals and more than 15 mm in diameter in post pubertal individuals -2 or more neurofibromatomas or one plexiform neurofibroma - freckling in the axilla or groin - Optic glioma - 2 or more Lisch nodules (iris haratomas) - a distinctive bony lesion (such as sphenoid dysplasia or psuedoarthrosis) -1st degree relative with NF1
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NF1 neuropathology |
- 15% have brain tumors, often present by age 6 - most are benign optic giomas and do not require treatment - little cog effect unless cranial radiation necessary - T2 hyperintensities in 60-7-% of children with NF1, freq occur in basal ganglia, cerebellum, thalamus, brainstem, and subcortical white matter - not consistently assoc w cog impairment - Macrocephaly/megalencephaly seen in 30- 50% of people with NF1 |
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NF1 co morbidities/mortality |
30-65% have LD- written expression, math, reading
30-50% have ADHD (equally occuring in males/females)
average lif span 50-60 years, milder forms have average life expectancy |
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NF1 presentation and disease course |
- clinical features present at different ages, may not meet Dx criteria until later childhood - most sx worsen over time - neurofibromatomas inc in puberty and during pregnancy - one exception is T2 Hyperintensities, which resolve by adulthood - clinical features vary from mild to severe and debilitating - cog deficits can be identified early and persist through life, children can have developmental delays - no recovery, deficits remain static |
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clinical trials for what med in NF1 |
lovastatin in children to improve learning- success in mouse models |
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NF1 neuropsychological expectations |
- leftward shift in IQ - FSIQ averages from 89-98 -ID Dx in 4-8% - 75% of children have academic trouble though not all meet crietria for LD - deficits in attn/exec Fx common - visuospatial weaknesses were first identified but recent study did not replicate findings of verbal> visual IQ. -lang deficits, esp in word list generation, naming, reading comprehension and written expression - manual dexterity, motor coord, balance affected - no deficits in motor speed once processing speed controlled for - verbal and visual mem intact -internalizing disorders (anx/dep) more common than externalizing, but poor impulse control can be assoc with ADHD - greater risk for social difficulties - present as socially awkward - not at greater risk for severe psych px |
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Tuberous sclerosis conplex |
A variably expressed, autosomally dominant neuro cutaneous disorder affecting numerous organ systems incl skin, heart, kidney, lungs, and brain but considerable overlap and neuro/cig status shouldn't be based on genetic mutation alone |
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Cortical tubers in TSC |
Cortical tubers- potato like in appearance lesions, proliferation of glial and neuronal cells and kids of 6 layered structure of the cortex/ variable in size and #. Focus of epileptiform discharges |
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Cortical tubers in TSC |
Cortical tubers- potato like in appearance lesions, proliferation of glial and neuronal cells and kids of 6 layered structure of the cortex/ variable in size and #. Focus of epileptiform discharges |
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Subependymal nodules in TSC |
Harmartomas that form in the walls of the ventricles. Usually a symptomatic but some evolve into subepeddymal giant cell astrocytomas, particularly in familial cases and those presenting before age 20 |
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Cortical tubers in TSC |
Cortical tubers- potato like in appearance lesions, proliferation of glial and neuronal cells and kids of 6 layered structure of the cortex/ variable in size and #. Focus of epileptiform discharges |
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Subependymal nodules in TSC |
Harmartomas that form in the walls of the ventricles. Usually a symptomatic but some evolve into subepeddymal giant cell astrocytomas, particularly in familial cases and those presenting before age 20 |
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Subependymal giant cell astrocytomas in TSC |
Slow growing tumor Most common in TSC (occurring in 10%) Tumors at the foramen of Munro can block CSF and lead to inc intracranial pressure |
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TSC co-morbidities |
-80-90% have epilepsy, often intractable - 45% have ID (children w/ TSC and ID at greater risk for psychiatric/beh Px) - 40-50% have autistic spectrum disorder (Inc risk of ASD with ID in this population) - 20-50% have ADHD, higher prevalance in children with seizures
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TSC mortality |
life expectancy variable and depends on severity of Sx - those with mild sx have normal life expectancy - those iwth life threatening sx like brain tumore, kidney and lung lesions may have shorter life expectancy |
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presentation of TSC |
- cortical tubers and cardiac rhabomyomas can be seen prenatally on US, and some present in infancy w/ seizures - global delays in preschool aged children - ADHD Dx in school age - anx and dep appear in adolesence and adulthood
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TSC disease course |
- variable those with profound intellectual impairment show little cognitive progression past the sensiorimotor stage - infants w early delays tend to remain delayed compared to peers - even children without early delays tend to fall behind peers during school years - NOT assoc with intellectual or beh regression |
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Recovery in TSC |
- no cure - AED used for seizures, not good candidates for epilepsy surgery bc of multiple seizre foci |
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Expectations on NP testing in TSC |
bimodal distribution of IQ, with a minority (30%) of ind in the profound IQ range and 70% near normal. Down shift of mean IQ to 93.
High rates of LD in those with near normal IQ
deficits in attn skills and EF seen in those with near normal IQ.
only 30% have normal language development
deficits in memory recall but recog is spared
more than 50% have behavioral outbursts including tantrums and self injury (ID is a risk factor but seen in children w near normal IQ also)
Severe psych probs are uncommon, though psychosis with temporal lobe epilepsy can be seen
anx and dep can develop in adolescence and adulthood
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Sturge Weber Syndrome (SWS) |
a neurocutaneous disorder with defining characteristic of facial capillary malformation or port wine birthmark (PWB), which usually affects the face in the opthalamic division of the trigeminal nerve
- other major characteristics include vascualr malformation of the brain (leptomeningeal angioma) - which ususally is seen on the same side as PWB affecting occipital and parietal lobes (bilateral brain involvement less common) and glaucoma.
- no known genetic basis and is non familial |
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leptomeningeal angioma (in SWS) |
capillary venous vascular malformation of the brain - a PWB inc risk of brain involvement by 10-20% and risk increases with size and extent of the birthmark |
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cerebral atrophy and cortical calcification in SWS |
most commonly lateralized and seen in occipital and parietal regions. Over time, calcification appears to spread into frontal areas- however it is unlikely to spread and more likely to be easier to capture on imaging over time |
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co-morbities with SWS |
- 75% of those with unilateral brain involvement and 95% with bilateral brain involvement have seizures; which typically occur on the side of the body contralateral to the PWB - headaches and migraines are common and can have sig impact on quality of life in adults - stroke like episodes can be assoc with seizures or migraines and present w/ weakness or sensory disturbance on the side contralateral to brain involvement. Motor weakness can persist or become permanent following prolonged/clustered seizures or a stroke like episode. - 18 fold increase prevalance of growth hormone deficiency seen - 50-60% dx with ID, risk factors include cerebral atrophy, cortical calcification, leptomeningeal angioma, and seizures that onset early and are poorly controlled |
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presentation of SWS |
neuro deficits evolve over time as the result of stroke like episodes and seizures - toddlers vulnerable to stroke like episodes from falls (Ind with SWS have to avoid recreational activities with risk for head injury) - most adults have some focal neuro deficit and hemiparesis |
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presentation of SWS- seizures |
usually begin in childhood but can present in adults that have been neurologicall normal - usually occur in 1st year with unilateral brain involvement - usually focal motor but can see complex partial seizures - status epilepticus can be seen, usually assoc w stroke like episode - seizures stabalize in late childhood then worsen again in adolescence - later seizure onset (after 9-12 months), good seizure control, and unilateral brain involvement are assoc with better neuro outcome - people w SWS vulnerable to neurological deterioration, thought to be secondary to venous occlusions and assoc hypoxia worsened by seizures - prognosis worse when seizures/stroke like episodes onset before 6 months - neurological deterioration is more common in infants and young children but can be present in adults - early onset dementia has been reported in 50s and 60s
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mortality- SWS |
life expectancy variable and depends on severity of Sx - those with mild sx have normal life expectancy - those with more severe Sx have shorter life expectancy
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recovery- SWS |
no cure AEDs to control seizures- some research shows better cog fx in children treated prophylactically compared to those treated after 1st seizure surgery for epilepsy also used B/C microvascular thrombosis is thought to contribute to neuro decline low dose ASA commonly recommended |
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expectations for neuropsych test results- SWS |
- few large studies - understanding NP Fx in SWS further complicated by variable course and outcome - there may be fluctuation even in the same individual - case studies have shown several risk factors for worse cognitive outcome: freq of seizures seizures onset in infancy more diffuse cortical involvement Hx of stroke like episodes
- 60% have IQ scores in range of ID, though scores can range from far below to above average - learning Px freq reported - attn px common - processing speed is slow - lower IQ and freq sezires inc risk for psych and beh px disruptive beh disorder most common in children, with noncompliance and oppositional beh reported - mood probs, esp anx, often seen in children - emotional distress related to size of PWB in children over age 10 - depression seen in adults who are cognitively intact - substanc erelated disorers and mood disorders most commonly dx psych conditions in adults - aggression and self injurious beh seen in children and adults with intellectual impairment - social px common
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Williams syndrome (ws) |
Mild to moderate cog deficits |
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Neuropathology-ws |
Reduction of cerebral volume, cerebellum preserved (reduced white matter volume preserved gray) splenium and isthmus) (linked to decreased activation in visual cortex during facial processing tasks)
occipitoparietal sulcus- linked to abnormal dorsal stream function activation in response to threatening faces, dorsal stream hypo activation observed during visual processing tasks |
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Co morbidities in ws |
70% failure to thrive as infants Valvar aortic stenosis px |
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Co morbidities in ws |
70% failure to thrive as infants Valvar aortic stenosis px |
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Mortality- ws |
Cardiac disease accounts for most cases of shortened lifespan |
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presentation and course- ws |
- motor delays and hypertonia in infancy - dev language is atypical- usually start using single words before pointing, and look at an adults face rather than where they are pointing -emergence of first word delayed 2 years, but once begin speaking- rate of development is typical -grammatical errors continue into adolescence - considered "talkers" and use language socially
by age 30, most have sensorineural hearing loss(can begin as early as late childhood)
majority of adults have diabetes or prediabetes
premature gray hair, wrinkling
hoarse voice
enhanced affinity for music, earlier interest, greater emotional response- rhythm and timbre are strengths |
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recovery- WS |
No cure music therapyand activities tend to lower anxiety and maladaptive beh. |
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expectations for neuropsych results- WS |
- avg FSIQ is 55, ranges from 40-90; few studies document IQ over 70. - verbal IQ exceeds nonverbal - impaired visuospatial cognition is a hallmark - in contrast, obj and face recognition are often intact - take a local/feature rather than global configurational approach in contructional tasks and processing faces- suggesting dorsal visual stream is dysfunctional and ventral visual stream is intact - auditory remote memory a relative strength, visual rote memory is deficient - greater deficits in spatial memory tasks than object memory tasks - reading relatively better than math (Adults with WS have 5th grade reading level)- but reading decoding often better than comprehension - fine and gross motor deficits - rate of ADHD higher than normal population - anx and persistent fears are common, 54-96% have specific phobias, GAD rate increases in adulthood - hypersociality - with people with WS as overly friendly (can be seen in infancy); however they lack social intelligence and judgment, leading to difficulty forming friendships and social isolation - children with WS exhibit conversational stereotypies - do well in open ended, less constrained social situations where they can take the initiative; struggle in constrained social context where they must adapt to the situation |
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22q11.2 delection syndrome |
AKA DiGeorge Syndrome, Shprintzen syndrome, or velo-cardio-facial syndrome |
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22q11.2 delection syndrome |
characterized by mulyiple congenital malformations, hypocalcemia, mild conductive hearing loss, and palatal defects
90% are de novo mutations,
10% inherited from parent in autosomally dominant pattern |
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22q11.2 delection syndrome
neuropathology |
decrease in total brain volume by about 10% (white matter more decreased than gray, frontal volume more preserved, parietal volume reduced- general anterior to posterior pattern of progressive volume reduction)
reduced cerebellar volume (assoc with decrease of vermis and pons)
hippocampal reduction (can be commensurate or disproportionate to overall volumetric decrease)
disorganized axonal tracts(parietaoparietal, frontofrontal, and frontotemporal connections)
cortical thinning (in parieto-occipital and orbitofrontal regions) |
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co- morbidities
22q11.2 delection syndrome |
75-80% have congenital heart defect ( account for most cases of mortality) 69% have palatal abnormalities that result in speech and feeding difficulties 30-40% have ADHD 30-40% have anx d/o, esp spec phobias and separation anx 10-30% have ASD 82-100% have learning difficulties 20-30% have mood disorders 25-30% dx w psychotic d/o |
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22q11.2 delection syndrome presentation and course |
dev delays often masked by health px in infancy, focus is on cardiac defects and palatal malformations
expressive language more delayed than receptive, many are non verbal until age 3- improves w time but higher order language remains impaired
controversial if these patients have non verbal LD. verbal stronger than non verbal but some studies only show 4-5 pt IQ discrepancy
have strong rote memory and good reading decoding compared to poor math, attn/EF, and mood/psychiatric disorders
avg age onset psychosis and schiz is late teens early 20s, subthreshold symptoms present in 30-50% of adolescents - subthreshold sx, anx/ocd sx, dep, and lower verbal iq scores are predictors of onset of psychosis in adolescence
adults w schiz perform more poorly on preforntal NP tasks, includ spatial working memory, strategy formation, verbal reasoning, visual recog, and attn- compared to those without schiz
- stimulant medications usually effective for attn, but dont respond as well to antipsychotics |
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22q11.2 delection syndrome
expectations for NP results |
- IQ ranges fr mild ID to avg, mean scored in borderline range
language skills better than nonverbal, though children perform worse on language testing than would be expected given verbal IQ scores, with weaknesses in expressive and pragmatic skills
- deficits in nonvebal skills, including visuospatial, visual perceptual, and visuomotor skills are common- px with math and numerical processing
- trouble manipulating quantities, calculation and word prob solving
-number reading and math facts are intact
- reading spelling and processing phonologically are areas of strength, though behind peers- reading comprehension lags behind.
- verbal better than vis mem
- better on rote verbal learning (lists) than complex verbal memory tasks (strories)
- visual, auditory, and spatial attn deficits seen, more problems as tasks load in complexity
_EF deficits common
- children tend to be rigid, perseverative, and infelxible in probklem solving approach
- deficits in gross motor more marked than fine motor
anx, specific fears, and OCD common
bland affect with minimal facial expression
risk of developing schiz 25 times that of general population
also greater risk for mood d/o |
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Adrenoleukodystrophy (ALD) |
X linked recessive d/o affecting CNS myelin and adrenal cortex
biochemically, there is defective oxidation of very long chain fatty acids (VLCFA) which accumulate in plasma, brain , and adrenal cortex
neurodegenerative= death 2-5 years from onset
males show greater deficits
heterozygous females may demonstrate mild to mod myeloneuropathy, typically after age 40, adrenal and cerebral involvement is rare
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ALD
4 main phenotypes in males |
SEE CHART pg 245
cerebal inflammatory (4 types, childhood cerebral is the classic type and most common (31-35%)
Adrenomyeloneuropathy Addison only asymptomatic
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ALD neuropathology |
inflammatory brain demylination (posterior pattern seen in 80%- demylination starts in the splenium of the corpus callosum and streads into parieto occiptal white matter
Arcuate fibers are spared
non inflammatory distal axonpathy- involves long tracts of spinal cord and associated with AMN phenotype |
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ALD comorbidity |
- 90% have adrenal insufficiency - 56% of adults have psych sx - 100% of males with cerebral inflammatory ALD have neurological deterioration, death occurs within several yrs of cerebral involvement
- death with males who have AMN occurs after several decades |
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ALD presentation and course |
- childhood develoment typically normal prior to onset - CCALD has onset btwn ages 3-8 with ADHD like Sx, followed by intellectual , beh, and neuro deterioration - minimally responsive state within 2 years of disease onset, followed by death - adolescent form is less severe and may first present with adrenal insufficiency, neuro dysfunction , or psych sx--- death within 1-2 years of cerebral involvement - for adults, mania and psychosis may be seen years before motor signs (abnormality of gait and upper motor neuron involvement)
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ALD therapies |
Adrenal hormone replacememt
low fat diet with lipid supplement awith lorenzo's oil normalizes plasma VLCFA but does not seem to alter progression unless asymptomatic - bone marrow transplant is the only effective long term tx if done at early stage of cerebral disease. after BMT, improvement can be seen in non verbal IQ- verbal remains stable. Children also have fewer beh difficulties after tx. - predictors of good outcome following BMT = few or no neuro deficits, nonverbal IQ greater than 80, less sig findings on MRI. A 68% 5 year survival rate for related and 54% for unrelated donors is reported |
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ALD neuropsych expectations |
no deficits for asymptomatic boys
possible decline in visual perceptual/motor skills with maturity
cognitive pattern similar to demyelinating diseases like MS
attn px usually seen first in children, psych px seen 1st in adults
greater non verbal than verbal deficits
memory deficits, particularly visual, in adults with AMN
EF deficits in children and adults
worsening motor, sensory, and beh probs as disease progresses |
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Klinefelter syndrome
(KS, 47,XXY) |
most common sex chrom aneuploidy seen in males
extra x chromosome
- tall stature, hypogonadism, fertility problems |
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KS neuropathology |
reduced overall brain volume= limbic, caudate nucleus, and cerebellum in particular, enlarged lateral ventricles
reduced overall tenporal lobe gray matter volume (worse on left than R)- presevration seen in those Tx with testosterone during development
inc rates of anomalous cerebral dominance= reduced hemispheric specialixation for language, prominent in superior temporal gyrus, inc activity in lang areas of R hemisph.
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co morbidity of KS |
35-65% have ADHD
5-10% have ASD
50-75% have LD, predominately Dyslexia
- inc mortality with median loss of 2.1 years |
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presentation and course
KS |
absent or subtle in early childhood
may have motor or speech delay
language milestones delayed
tall stature in childhood but more apparent in adolescence
adults about 3 inch taller than predictions based on fam hx
testosterone deficiency results in incomplete puberty- reduced or diminished growth of facial, chest, pubic hair
microorchidism (small testes) in almost all, gynecomastia in 25-30 %
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tx- ks |
testosterone replacement therapies
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KS
Neuropsych expectations |
IQ generally avg but 5-10 pts lower than siblings, polulation cohorts
better non verbal than verbal, deficits in specific language skills (higher level, verbal expression) and verbal exec tasks
dyslexia common
language deficits more common as children not as pronounced in adults
visual mem performance enhanced
High rate of ADHD (more inattentive than hyperactive)
proc speed slow
other deficits in: strength, agility, hand/finger dexterity, hand speed, running speed
high rates of dep/anx, including social anx and withdrawal
shy, emotionally sensitive, socially immature
peer difficulties are common
higher rates of ASD and psychosis
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fragile X syndrome (FXS) |
repetition in the CGG trinucleotide sequence at Xq27.3, in typical individual, up to 44 repeats. 45-54 repeats in the gray zone (do not have expression of the disease but repeats may expand with future generations)
premutation carriers have 55-200 repeats, full mutation over 200 repeats
causes deficit or absence of FMR1 protein
males more affected than females (females have 2 X chromosomes, so if mutation only on one, than the other X can produce the protein and lessen impact of disease)
LEADING CAUSE OF INHERITED ID AND MOST COMMON SINGLE GENE DISORDER ASSOC WITH AUTISM |
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neuropathology
FXS |
most imaging studies done with females and higher Fx adults, which may limit findings
- enlarged hippocampus, caudate nucleus, thalamus, and amygdala (caudate nucleus 20% larger/correlates with inc severity of autistic beh and stereotypic tendancies)
- reduction in size of cerebellar vermis - dysmorphia of cerebellar vermis and caudate nucleus - predictive of poor cognitive testing and lower IQ |
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co morbidity FXS |
10-20% epilepsy, more common in males (pattern in EEG is unique to FXS, resembles benign rolandic epilepsy) seizures often resolve after childhood or adoles.
40% of premutation males and 10% of females develop FXS assoc tremor/ataxia syndrome with progressive gait ataxia, intention tremor, parkinsonianism, peripheral neuropathy, STM loss and Exec dysfunction
45-47% of males Dx autism
70-90% of males and 30-50% of females Dx ADHD (hyperactivity, impulsivity, inattention, hyperarousal)
80% males and 30% females have ID- males mod to severe; females more often mild
Lifespan is normal |
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presentation, course
FXS |
most males have ID, females less severe cognitive and beh/soc Px
premutation carriers have normal IQ, but ADHD, anx, shyness, and social Px seen - some studies say also at risk for EF deficits
developmental delays usually the first sign, mean dx age is 8 years
develop large testes in puberty. inc in size until 2-4 times normal size at age 15, then stabalizes
fertility is normal but cognition interferes with reproduction
no cure |
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FXS
Neuropsych results |
Mean IQ for males in mid 40s
females=mild ID to Avg
in females without ID, inc risk of math disability seen as early as Kindergarten
reading is a relative strength
"cluttering" speech- incomplete sentences, 203 word phrases, echolalia, palilaia, perseveration, poor articulation, stuttering
memory better for structures more cohensive info (stories) than for abstract info
EF deficits greater than would be expected by IQ
proc speed and attn generally commensurate with IQ
hypotonia, balance probs, fine motor, and oral motor skills weak
poor etye contact abd gaze aversionin males
rigid, difficulty with transitions, social anx and abnormal social beh
approach- withdrawal behavior (they want to approach but instead withdraw)
self injurious beh more commonly in males |
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Turner syndrome (TS) |
missing or abnormal second X chromosome (only occurs in females)
characteristic physical features (short stature, webbed neck) cradiovascular malformations, congenital heart disease, kidney malformations |
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TS neuropathology |
decreased volumes or parietal and occipital cortices (assoc with deficits in visuospatial processing)
abnormal structure and function of amygdala, insula, anterior cingulate, ventromedial frefrontal cortex, and orbitofrontal cortex- related to social/affective difficulties
dysfunctional frontoparietal circuitry- assoc with deficits in visuospatial working mem
agenesis or anatomical differences in the corpus collosum |
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TS comorbidities |
17-45% have cardiovascular malformations - higher prevalnec in those with 45, X as opposed to mosaic karyotype
avg height 4'7 - almost all short stature
osetoporosis, inferitilty poor estorgen production and absent overian tissue
30% have thyroid d/o , most often hypothyroidism
25% ADHD
45-55% dx with math disability
reduced life expectancy up to 13 years, usually related to cardiac malformations |
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presentation and course- TS |
developmental motor delays early
45, X usually dx earlier than mosaicism
media age of dx is 6 estrogen/progesterone repleacement usually required for breast dev and bone density
tx results in improvement in processing speed, motor skils, and math
growth hormone initiated in childhood |
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expectations for NP results- TS |
traditional features of NLD, but considerable variability in neurocognitive profile
mean IQ 92-100, sig stronger verbal than non verbal IQ (though the discrepancy less apparent over time)
nonverbal deficits are a hallmark of TS
math disabilities common
early motor deficits
risk for early hearing loss
socially immature, lack connectedness w peers,
poor social competence
trouble reading social and non verbal cues
less interested in sex and sexual relationships
inc risk depression
struggle w issues related to fertility |
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Phenylketonuria (PKU) |
mutation in the phenylaline hydroxylase gene, which inhibits the metabolism of Phe into Tyr
requires a Phe restricted diet, which can mitigate many cognitive and neuro deficits
autosomal recessive disorder
more common in North Am and Europe and less common in Asia and Africa
usually identified through newborn screening blood tests |
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neuropathology PKU- untreated |
hypomyelination and gliosis in systems that myelinate postnatally
progressive white matter degeneration (less freq and mostly in adults)
delayed or arrest in development of cerebral cortex
diffuse cortical atrophy and reduced dendritic arborization seen |
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neuropathology PKU- treated |
white matter abnormalities (abnormal myelination, T2 hyperintensities- most commonly occipital parietal but can extend to frontal parietal)
volume loss- in cerebrum, corpus collosum, hippocampus, and pons
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comorbidities PKU |
75% of untreated have sig neurological dysfunction
- 5% untreated have progressive neurological d/o, usually supranuclear motor disturbance
- 13-46% ADHD
treated have a normal lifespan |
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presentation and course- PKU |
the course is sig different if treated early
untreated infants- musty odor. hypotonia, irritability, feeding difficulties
4-6 months, progressive psychomotor retardation and seizures
cog deterioration over next 3-4yrs
sig beh px, including obsessive compulsive rituals, self injurious beh, extreme tactile sensitivity
IQ below 50
IF TREATED- late treated have mostly IQs in mild to mod ID range, learning probs even if IQ is avg
treated early0 more subtle neuro deficits
low Phe diet is Tx
age of initation of tx sig assoc with degree of cog imp
white matter abnormalities reversible w treatment
stimulants can help w ADHD
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NP expectations- early Tx PKU |
avg range but lower than sibling controls
reading and spelling intact, math deficient
academic scores related to length of dietary treatment- better scores for those tx longer
reduced processing speed primary deficit in adults
fine motor deficits
at risk for emotional and beh px, incl hyperactivity, impulsivity, and limited task persistence
poor social competence and at risk for social isolation
dep common, esp in women
anxiety also common, agoraphobia linked to higher Phe levels |
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Prader Willi Syndrome (PWS) |
lack of paternally expressed genes in the q11-13 region of chromosome 15
excessive eating is a hallmark (hyperphagia)
also characterized by neonatal hypotonia, hypogonadism, obesity, and mild to mod ID |
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neuropathology - PWS |
morphological changes in pituitary gland, reduction in # of cells in paraventricular nuclues of thalamus, ventriculomegaly, decreased tissue volume in parietal occipito lobe, sylvian fissure polymicrogyria, and incomplete insular closure
connectivity abnormalities difficusely
abnormalities in brain regions assoc with eating- differences in amygdala and orbitofrontal cortex, including delayed response to glucose ingestion in arease related to satiety |
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comorbidities- PWS |
majority have IQ in mild to mod ID
25% ASD, inc risk of psych disorders
hypotonia at birth and through lifespan
hypogonadism- at birth, females have pubery but abnormal menstruation and early menopause, males do not progress past mid puberty
respiratory issues including neurmuscular OSA
GI complications, swallowing OX, decreased salivia production, decreased or absent ability to vomit
obesity- with assoc type II diabetes and cardiovascular px
short stature, avg height 5 ft
diminished lifespan, most often related to respiratory px, choking, gastric necrosis and rupture |
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presentation and course of PWS |
2 clinical phases_ neonatal and hyperphagic
first phase at birth and lasts 1-3 years: hypertonia, feeding difficulties, poor suck, lethary, failure to thrive- motor and labguage delayed
hyperphagic phase starts age 2-6. interest in food becomes more normal then excessive
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recovery PWS |
no cure growth hormone tx used dietary recommendations complete food restrictions often recommended
SSRI for self injurious and compulsive beh, antipsychotics for aggression and disruptive beh |
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NP expectations- PWS |
IQ in mild to mod range of ID, mean IQ 62-73, range from 39-96
adaptive functioning typically worse than IQ
performance IQ generally higher than verbal
speech deficits above what would be expected for cognitive functioning, poor speech sound development and reduced oral motor skills
more academic difficulties than suggested by IQ
hypotonia and motor px throughout life
proeoccupation w food
compulsive beh not food related also seen
ritualistic, self injurious beh (esp skin picking)
temper tantrums, rigidity, low frustration tolerance ,impulsivity
beh px diminish in older adults
overlap with ASD sx
greater risk for psych px, incl bipolar with psych features, nonpsychotic mood d.o, and anx |
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angelman syndrome (AS) |
lack of maternally expressed geners n the q11- q13 region of chromosome 15
severe ID, ataxia, epilepsy, severe speech.lang delays, repetitive/stereotyped beh, sensory seeking beh
happy dispostion with easily provoked and inappropriate laughter |
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neuropathology of AS |
general normal brain structures
characteristic EEG pattern (see pag 256 for detail on EEG pattern)
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co morbidities of AS |
80-90% epilepsy 100% movement or balance disorder w ataxia of gait 100% have severe developmental delay, particularly in speech and language
sleep disorders common, freq night waking, early wakening, decreased need for sleep - normal lifespan |
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presentation and course- AS |
dev delay noted around 6 mon, platuea in development around 24-30 months
seizure onset age 1-5 years- difficult to control, often need multiple AEDs
hyperkinetic movements of trunk and limbs in infancy, 10% fail to achieve walking
motor streotypes (flapping, waving) common
facial characteristics more pronounced in adolesence and adulthood
no cure, may have some benefot from stimulants for htyperactivity, speech tx focused on non verbal communication, incl gestures and assited devices is essential |
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expectations for NP results- AS |
few studies as testing difficult due to intattention, hyperactivity, and lack of speech and motor control.
speech absent or a few words
receptive better than expressive but far below expectation for age
attn span short, hyperactivity
hypotonia of limbs and trunk
freq laughter, excitable as early as infancy
more social than expected given IQ
eye contact good, seek out interaction
fascination w water and reflective surfaces |
