Chromosomal and Genetic Syndromes Flashcards
Three disorders of neurofibromatoses
neurofibromatosis type 1 (NF1) - skin and bone abnormalities resulting from tumors growing along the nerves
most common and associated with ND deficits
neurofibromatosis type 2 (NF2) - bilateral acoustic schwannomas on the eighth cranial nerve, meningiomas, and ependymomas.
schwannomatosis - associated with schwannomas and chronic pain
All have the development of nerve sheath tumors in common.
Neurofibromatosis type 1
neurocutaneous autosomally dominant genetic disorder
diagnostic criteria includes at least two:
- Six or more café-au-lait macules
- Two or more neurofibromas
- Freckling in groin
- Optic glioma*
- Two or more Lisch nodules (iris abnormality)
- A distinctive bony lesion
- A first-degree relative with NF1
NF1 neuropathology
Brain tumors are seen in 15% of people before age 6, usually optic gliomas
- optic gliomas thought to NOT have cognitive impact but radiation to treat can effect functioning
Macrocephaly (30–50%)
Hyperintensities: focal lesions to areas of basal ganglia, cerebellum, thalamus, brainstem, and subcortical white matter (these are not associated with degree or presence of cog impairment)
- resolve by early childhood
NF1 neurocognitive sequelae
- Leftward shift of IQ (89-98)
- 4-8% ID
- 30–65% SLD
- Language deficits
- 30–50% ADHD (EF too); occurs equally in boys and girls
- Higher incident of internalizing disorders and social difficulties
Tuberous sclerosis complex
autosomally dominant neurocutaneous disorder
- multi-system genetic disease that causes non-cancerous (benign) tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin.
arises from one of two genes: TSC1 or TSC2
Tuberous sclerosis complex brain lesions
Cortical Tubers - benign lesions, potato-like appearance on MRI (leads to seizures)
Subependymal Nodules - form in the walls of the ventricles
Subependymal Giant-Cell Astrocytomas (SEGA) - most common brain tumor
Tuberous sclerosis complex clinical manifestations
80–90% seizures
45% ID
40–50% ASD
25–50% ADHD
50% behavior problems (aggression, temper tantrums, self-injury)
The term “tuberous sclerosis-associated neuropsychiatric disorders” (TAND) is now used to describe the constellation of intellectual, behavioral, and psychosocial difficulties associated with TSC.
Sturge-Weber syndrome
neurocutaneous disorder with the defining characteristics:
- port-wine birthmark (facial capillary malformation)
- vascular malformation of the brain (leptomeningeal angioma) usually seen in occipital and temporal lobes on same side as port-wine birthmark
- most people with vascular malformation of the brain have seizures - contralateral side to port wine birthmark
- glaucoma (30–60%)
Common neurocutaneous disorders
NF1 (and 2)
Tuberous sclerosis complex
Sturge-Weber syndrome
Sturge-Weber syndrome clinical manifestations
- Seizures (75-95%) typically occur on the side of the body contralateral to the port-wine birthmark
- Headaches and migraines are common
Sturge-Weber syndrome neuropsychological expectations
50–60% ID
Attention and processing speed
Disruptive behavior
Williams syndrome
spontaneous genetic condition, caused by a deletion of 26 to 28 genes on chromosome 7
connective tissue abnormalities, cardiovascular disease (50-75%), and characteristic facial dysmorphology, including elf-like features
William syndrome neurobehavioral characteristics
- Hypersociability with poor social judgment
- Majority have IQ in the range of ID, with uneven skills.
**Verbal (reading, memory) > nonverbal (math, memory)
Hallmark: impaired visuospatial functioning but object/face recognition intact…
“Individuals with WS tend to take a local/featural rather than a global/configurational approach when completing constructional tasks and processing faces, suggesting that the dorsal visual stream is dysfunctional while the ventral visual stream remains intact.” - Fine and gross motor deficits
- 85–95% sound hypersensitivity
- 50-95% anxiety/specific phobias
- 50–65% ADHD
22q11.2 Deletion Syndrome/DiGeorge syndrome
90% spontaneous mutations
multiple congenital anomalies including cardiac malformations (75%), hypocalcemia, mild conductive hearing loss, and palatal defects (70%)
22q11.2 Deletion Syndrome clinical manifestations
- 30–40% ADHD
- 30–40% anxiety disorders, especially specific phobias and separation anxiety
- 10–30% ASD.
- 82–100% have learning difficulties.
- 20–30% mood disorder, including major depression and bipolar disorder.
- 25–35% psychotic disorder greatest concern
22q11.2 deletion syndrome neuropsychological expectations
- borderline IQ
- verbal (reasoning, attention, memory) > visual (deficits: visuospatial, visual-perceptual, and visual-motor skills, visual memory and attention)
- Math difficulties are common
- Gross motor deficits > fine motor deficits
Adrenoleukodystrophy
neurodegenerative (demyelinating) in nature, with death occurring within 2 to 5 years after clinical onset.
X-linked (males show greater deficits), recessive disorder affecting CNS myelin and adrenal cortex which then results in abnormal breakdown of very-long-chain fatty acids (VLCFA), which then accumulate in plasma, brain, and adrenal cortex.
Adrenoleukodystrophy neuropsychological expectations
No deficits in asymptomatic
Children and adults with ALD present with a cognitive pattern typically seen in other demyelinating diseases such as multiple sclerosis:
- Attention problems are one of the first clinical symptoms to emerge in children
- psychiatric symptoms are among the first in adults.
Greater deficits are seen in nonverbal/visuospatial tasks as opposed to verbal IQ tasks, occurs over time and related to progressing cerebral lesions in parietal and occipital regions visuospatial is an excellent predictor of neurocognitive functioning after stem cell transplant
Klinefelter syndrome
only seen in males
resulting from the presence of an extra X chromosome
associated with characteristic physical features including tall stature, hypogonadism, and fertility problems.
most not diagnosed until after puberty when testosterone deficiency results in slow or incomplete pubertal development
Klinefelter syndrome clinical manifestations
- 35–65% ADHD.
- 5–10% ASD.
- 50–75% LD, predominantly dyslexia
Higher rate of psychotic symptoms
Characteristics of Angelman syndrome
Fair hair, blue eyes, dysmorphic features (wide smiling mouth, thin upper lip, pointed chin), epilepsy, ataxia, microcephaly, happy disposition, hand flapping, intellectual disability, sleep disturbance, possible autistic features, and love of water and music
