Genetic Disorders Flashcards
Criteria for Neurofibromatosis Type 1
2 or more of the following:
- 6+ cafe au lait macules more than 5 mm in diameter (prepubertal) or greater than 15 mm (postpubertal)
- 2+ neurofibromas or one plexiform neurofibroma
- Freckling in the axilla (armpit) or groin
- Optic glioma
- 2+ Lisch nodules (iris hamartomas)
- a distinctive bony lesion (such as sphenoid dysplasia or pseudoarthrosis)
- a first degree relative with NF1
Neurofibroma
Nerve tumor (peripheral)
Plexiform Neurofibroma
Nerve tumor arisen from a bundle of nerves
What is Neurofibromatosis?
Development of nerve sheath tumors
There is NF1, NF2, and schwannomatosis. NF1 is the most common and is associated with neuropsychological deficits
Neurofibromatosis 1
a neurocutaneous autosomally dominant genetic disorder with symptoms affecting the CNS and skin. Average life expectancy: 50-60 years
Chromosome 17
What % of people with NF1 have brain tumors?
15%, most by 6 years of age
Neuroimaging: NF1
T2 hyperintensities; most frequently in the basal ganglia, cerebellum, thalamus, brainstem, and subcortical white matter; not consistently associated with the presence or degree of cognitive impairment.
% of people with NF1 have macrocephaly/megalencephaly
30-50%
% of people with NF1 have a LD/ADHD
75%
30-65% LD
30-50% ADHD
NF1 NP Profile
“Leftward shift” of IQ = average 89-98
75% of children with NF1 are estimated to have learning difficulties
Deficits in attention, executive function, manual dexterity, coordination, and balance
No deficits seen in memory or motor speed.
What is Tuberous Sclerosis Complex?
variably expressed, autosomally dominant neurocutaneous disorder affecting multiple organ systems including the skin, heart, kidney, lungs, and brain. Genes: TSC1 (chromosome 9q34; generally milder) or TSC2 (chromosome 16p13.3)
Key Characteristics of Tuberous Sclerosis Complex
- Cortical Tubers
- Facial angiofibromas/hypomelanotic macules
- Shagreen patch
- Subependymal nodules
- Subependymal giant-cell astrocytoma (SEGA)
- Cardiac rhabdomyoma
- Lymphangiomyomatosis
- Renal angiomyolipoma
- Epilepsy
Cortical Tubers
potato-like lesions as a result of proliferation of glial and neuronal cells and loss of the 6-layered structure of the cortex; epileptiform discharges
Subependymal Nodules
hamartomas (noncancerous mass) that form in the walls of the ventricles; usually asymptomatic, some will evolve into subependymal giant-cell astrocytomas
Subependymal Giant-Cell Astrocytoma (SEGA)
slow-growing tumor that is most common in TSC (10% of individuals); if at the foramen of Monro, can block CSF, which can lead to increased intracranial pressure
TSC NP Characteristics
Intellectual disability (45%); Autism (40-50%) Deficits in attention, EF (working memory, organization, planning), language (expressive vocabulary, grammar), memory recall (spared recognition)
% of people with TSC diagnosed with epilepsy
80-90%; seizures typically begin in infancy
What is Sturge-Weber Syndrome?
no genetic basis, nonfamilial; neurocutaneous disorder with the defining characteristic of a facial capillary malformation or port-wine birthmark (PWB; trigeminal nerve). Also vascular malformation of the brain (leptomeningeal angioma) and glaucoma. Cerebral atrophy and cortical calcification (commonly lateralized)
Other clinical characteristics of Sturge-Weber Syndrome
Seizures, stroke-like episodes (seizures, migraines, sensory disturbance); growth hormone deficiency
% of people with Sturge-Weber Syndrome with Intellectual Disability
50-60%
Sturge-Weber Syndrome NP Profile
Not a lot of research. Some suggestion of deficits in language comprehension, word-list generation, and verbal memory. Depends on what areas are affected (e.g., seizures, calcification). Low IQ and frequent seizures.
Seizures and Sturge-Weber Syndrome
75% of people with unilateral brain involvement and 95% of those with bilateral brain involvement suffer from seizures, usually on the side of the body contralateral to the PWB.
What is Williams Syndrome?
mild to moderate cognitive deficits with an uneven NP profile, connective tissue abnormalities, cardiovascular disease, and characteristic facial dysmorphology, including elf-like features.
What is Williams Syndrome caused by?
Deletion of 26 to 28 genes on chromosome 7, spontaneous genetic mutation.
What syndrome is associated with deletion of 26-28 genes on chromosome 7?
Williams Syndrome
What syndrome is associated with abnormalities on chromosome 17?
Neurofibromatosis Type 1
Williams Syndrome characteristics:
reduction of cerebral volume with preservation of cerebellar volume (gray matter preserved, generally, white matter reduction); narrowing of the corpus callosum (splenium and isthmus); abnormal cell density in the primary visual cortex; reduced sulcal depth in the Intraparietal/Occipitoparietal sulcus (visuospatial deficits); abnormal neural pathways (increased amygdala activation in threatening scenes; reduced activation with threatening faces - possibly related to hypersocial and anxious traits; dorsal stream hypoactivation during visual processing tasks)
Basically, visuospatial and facial processing difficulties
% of people with Williams Syndrome develop cardiovascular disease
50-75%; accounts for most cases of shortened lifespan
% of people with WS diagnosed with visual acuity problems
50%
% of people with WS with hypersensitivity to sound
85-95%
Correlation between WS and ID
Majority have ID, greater deletions, higher risk for ID
WS NP Profile
IQ average is 55, verbal tends to exceed nonverbal, hallmark sign: visuospatial impairment; object and face recognition intact; hypersociability, anxiety
