Genetic Disorders

Question 1

Criteria for Neurofibromatosis Type 1

Answer 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

Question 2

Neurofibroma

Answer 2

Nerve tumor (peripheral)

Question 3

Plexiform Neurofibroma

Answer 3

Nerve tumor arisen from a bundle of nerves

Question 4

What is Neurofibromatosis?

Answer 4

Development of nerve sheath tumors

There is NF1, NF2, and schwannomatosis. NF1 is the most common and is associated with neuropsychological deficits

Question 5

Neurofibromatosis 1

Answer 5

a neurocutaneous autosomally dominant genetic disorder with symptoms affecting the CNS and skin. Average life expectancy: 50-60 years
Chromosome 17

Question 6

What % of people with NF1 have brain tumors?

Answer 6

15%, most by 6 years of age

Question 7

Neuroimaging: NF1

Answer 7

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.

Question 8

% of people with NF1 have macrocephaly/megalencephaly

Answer 8

30-50%

Question 9

% of people with NF1 have a LD/ADHD

Answer 9

75%
30-65% LD
30-50% ADHD

Question 10

NF1 NP Profile

Answer 10

“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.

Question 11

What is Tuberous Sclerosis Complex?

Answer 11

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)

Question 12

Key Characteristics of Tuberous Sclerosis Complex

Answer 12

• Cortical Tubers
• Facial angiofibromas/hypomelanotic macules
• Shagreen patch
• Subependymal nodules
• Subependymal giant-cell astrocytoma (SEGA)
• Cardiac rhabdomyoma
• Lymphangiomyomatosis
• Renal angiomyolipoma
• Epilepsy

Question 13

Cortical Tubers

Answer 13

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

Question 14

Subependymal Nodules

Answer 14

hamartomas (noncancerous mass) that form in the walls of the ventricles; usually asymptomatic, some will evolve into subependymal giant-cell astrocytomas

Question 15

Subependymal Giant-Cell Astrocytoma (SEGA)

Answer 15

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

Question 16

TSC NP Characteristics

Answer 16

Intellectual disability (45%); Autism (40-50%)
Deficits in attention, EF (working memory, organization, planning), language (expressive vocabulary, grammar), memory recall (spared recognition)

Question 17

% of people with TSC diagnosed with epilepsy

Answer 17

80-90%; seizures typically begin in infancy

Question 18

What is Sturge-Weber Syndrome?

Answer 18

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)

Question 19

Other clinical characteristics of Sturge-Weber Syndrome

Answer 19

Seizures, stroke-like episodes (seizures, migraines, sensory disturbance); growth hormone deficiency

Question 20

% of people with Sturge-Weber Syndrome with Intellectual Disability

Answer 20

50-60%

Question 21

Sturge-Weber Syndrome NP Profile

Answer 21

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.

Question 22

Seizures and Sturge-Weber Syndrome

Answer 22

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.

Question 23

What is Williams Syndrome?

Answer 23

mild to moderate cognitive deficits with an uneven NP profile, connective tissue abnormalities, cardiovascular disease, and characteristic facial dysmorphology, including elf-like features.

Question 24

What is Williams Syndrome caused by?

Answer 24

Deletion of 26 to 28 genes on chromosome 7, spontaneous genetic mutation.

Question 25

What syndrome is associated with deletion of 26-28 genes on chromosome 7?

Answer 25

Williams Syndrome

Question 26

What syndrome is associated with abnormalities on chromosome 17?

Answer 26

Neurofibromatosis Type 1

Question 27

Williams Syndrome characteristics:

Answer 27

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

Question 28

% of people with Williams Syndrome develop cardiovascular disease

Answer 28

50-75%; accounts for most cases of shortened lifespan

Question 29

% of people with WS diagnosed with visual acuity problems

Answer 29

50%

Question 30

% of people with WS with hypersensitivity to sound

Answer 30

85-95%

Question 31

Correlation between WS and ID

Answer 31

Majority have ID, greater deletions, higher risk for ID

Question 32

WS NP Profile

Answer 32

IQ average is 55, verbal tends to exceed nonverbal, hallmark sign: visuospatial impairment; object and face recognition intact; hypersociability, anxiety