Genetics/congenital/metabolic

Question 1

What is Friedreich ataxia?

Answer 1

Autosomal recessive disorder characterized by progressive ataxia that usually affects the arms more than the legs. Also demonstrates severe dysarthria. Usually presents in childhood. Classically associated with loss of reflexes, spasticity, and extensor plantar responses, high-arched feet, hammer toes, and impaired vibration and position sense. Caused by a mutation of the FXN gene on chr 9 (produces a protein called frataxin) leading to increased trinucleotide repeats. Can be associated with sensorineural hearing loss, DM, impaired glucose tolerance, hypertrophic cardiomyopathy with abnormal ECG.

Question 2

What is inherited episodic ataxia (EA)?

Answer 2

Two inherited syndromes characterized by episodes of ataxia, vertigo, nausea, and vomiting. EA-1 is caused my mutations to voltage-gated potassium channels and has brief episodes that are associated with myokymia (facial muscle fasciculations. EA-2 involve mutations to P/Q type voltage-gated calcium channels, and attacks last longer (several minutes) with interictal nystagmus; a progressive

Question 3

What is autosomal dominant spinocerebellar degeneration?

Answer 3

Cerebellar ataxia caused by a trinucleotide (CAG) repeat which affects P/Q type voltage-gated calcium channels. Presents in early adulthood and can cause mild-to-moderate cognitive decline

Question 4

What are the neurotrasmitter changes in hepatic encephalopathy?

Answer 4

Increased brain glutamine concentrations, depressed glutamatergic neurotransmission, and increased expression of peripheral-type benzodiazepine receptors

Question 5

What are complications of central pontine myelinolysis?

Answer 5

Acute confusional state, spastic quadriparesis, locked-in syndrome, dysarthria, and dysphagia

Question 6

What is diabetic proximal motor neuropathy (diabetic amyotrophy)?

Answer 6

Severe thigh and back pain, followed within weeks by mild to severe hip and thigh muscle weakness with muscle atrophy; usually affects older type 2 diabetics

Question 7

What nerve are susceptible to compression in diabetes?

Answer 7

Median nerve at the wrist, ulnar nerve at the elbow and peroneal nerve at the knee

Question 8

What is the genetic problem in Huntington disease?

Answer 8

Unstable CAG repeat on chromosome 4

Question 9

What is Sturge-Webber syndrome (aka encephalofacial angiomatosis)?

Answer 9

Congenital disturbance that produces facial cutaneous angiomas (port-wine nevus over the distribution of the 1st division of CN V) along with intracranial abnormalities such as leptomeningeal angiomas. Patients often exhibit mental retardation and hemiparesis or hemiatriophy on the side of the body opposite of the nevus. Seizures can occur. The intracranial angiomas do not usually develop if the nevus does not involve the upper face

Question 10

What is Landau-Kleffner syndrome?

Answer 10

Associated with loss of language function and an abnormal EEG during sleep

Question 11

What is West syndrome?

Answer 11

A severe epilepsy syndrome composed of the triad of infantile spasms, an interictal electroencephalogram (EEG) pattern termed hypsarrhythmia, and mental retardation

Question 12

What substance accumulates in Gaucher disease?

Answer 12

Glycosylceramide - caused by a beta-glucocerebrosidase deficiency

Question 13

What substance accumulates in metachromatic leukodystrophy?

Answer 13

Galactosyl sulfatides - due to arylsufatase A deficiency

Question 14

What substance accumulates in Krabbe disease?

Answer 14

Galactocerbroside - due to galactosylceramidase deficiency

Question 15

What type of brain cell is most affected by chronic liver failure?

Answer 15

Astrocytes - causes an increase in Alzheimer type II astrocytes

Question 16

What is the vision loss seen in tobacco-alcohol amblyopia and vitamin B12 deficiency?

Answer 16

An enlargement of the blindspot in the eye, called a centrocecal scotoma

Question 17

What is Canavan disease?

Answer 17

Causes developmental regression by age 6 months due to a defect in N-acetylaspartic acid metabolism (increased systemically including in the CNS). Changes in brain white matter are widespread and may result in spongiform appearance. These infants have macrocephaly

Question 18

What is Leber optic atrophy?

Answer 18

A mitochondrial disease that causes loss of central vision (centrocecal scotoma)

Question 19

What is Pelizaeus-Merzbacher disease?

Answer 19

A demyelinating disorder that affects children and is a part of the sudanophilic leukodystrophies (the involved white matter stains with Sudan staining). Symptoms occur in the first months of life, but patients may survive into their 30s

Question 20

What is the most appropriate treatment for the hemangioblastomas seen in vHL?

Answer 20

Surgical resection due to a high risk of intracranial bleeding

Question 21

What is Aicardi syndrome?

Answer 21

A genetic condition that leads to agenesis of the corpus callosum, retardation, epilepsy, vertebral anomalies, and chorioretinitis

Question 22

What is Hartnup disease?

Answer 22

Causes intestinal malabsorption of tryptophan and other neutral amino acids. Tryptophan is a precursor for nicotinamide so children can develop a rash similar to the one seen in pllagra and they may get episodic ataxia, as well as have developmental delay. Autosomal recessive

Question 23

What is Sturge-Weber syndrome?

Answer 23

STURGE: seizures, trigeminal port-wine stain/tram track calcifications on gyri, unilateral weakness (hemiparesis), retardation in some, glaucoma, eye problems (e.g. buphthalmos = eye enlargement)
Neurologic symptoms occur on the side OPPOSITE the port wine stain. These could be seizures or hemiparesis.

Question 24

What is abetalipopreteinemia (Bassen-Kornzweig syndrome)?

Answer 24

It is a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins. It leads to progressive ataxia, peripheral neuropathy, retinitis pigmentosa and acanthocytosis, which begins in childhood. Supplementation with vitamin E may help slow progression

Question 25

What autosomal dominant disorder is associated with adenoma sebaceum (angiofibromas)?

Answer 25

Tuberous sclerosis

Question 26

What mnemonic is helpful for remembering tuberous sclerosis?

Answer 26

HAMARTOMA:
Hamartoma
Adenoma sebaceum
Mitral regurgitation
Ash-leaf spots
Rhabdomyoma
(Tuberous sclerosis)
dOminant inheritance
Mental retardation (65%)
Angiomyolipoma (of kidney)

Question 27

What genetic disease has retinal phakomas (gliomatous tumors of the retina)?

Answer 27

Tuberous sclerosis - part of principal criterion for making the diagnosis. Do not require treatment

Question 28

What structures may get calcified in the CNS in a patient with tuberous sclerosis?

Answer 28

Subependymal glial nodules

Question 29

What is the shape of the brain in Down syndrome?

Answer 29

The brain is typically foreshortened (smaller) with a simplified gyral pattern and small frontal lobes

Question 30

What symptom usually presents in Chiari type 1 vs type 2 malformations?

Answer 30

Cerebellar signs - May not present until adulthood. Chiari type 2 often produces hydrocephalus with retardation.

Question 31

What nerves are damaged in Friedrich’s ataxia that lead to ataxia?

Answer 31

Causes degeneration of the dorsal and ventral spinocerebellar tracts in the spinal cord

Question 32

What are the genetics of Friedrich’s ataxia?

Answer 32

Expansion of a GAA repeat of the FXN gene which codes for the frataxin protein. On chromosome 9. Autosomal recessive

Question 33

What nerves in the spinal cord are damaged in Friedrich’s ataxia?

Answer 33

The sponocrebellar tracts (ataxia) and the dorsal columns (peripheral neuropathy)

Question 34

What is Parsonage-Turner syndrome?

Answer 34

It is an acute brachial plexopathy. Usually begins with acute onset of neck, shoulder, or upper arm pain, followed by rapid evolution of weakness of the proximal arm. Can be inherited as an autosomal dominant syndrome

Question 35

What is familial dysautonomia (Riley-Day disease)?

Answer 35

AR disorder of primarily Jewish children. Characterized by small fiber neuropathy so affects pain and temp, as well as sympathetic and parasympathetic ganglia leading to autonomic features (e.g. loss of tears on crying, corneal ulceration, excessive perspiration, abnormalities of BP control, dysphagia, recurrent vomiting, and gastric and intestinal dilation). There is also absence of papillae of the tongue