Question

• Describe the genetic components, pathophysiology, and major neurologic features of neurofibromatosis, Cri du chat syndrome, Tay-Sachs disease, and Parkinson disease (early onset).

Answer 1

#.1. Tay Sachs Disease

Etiology: lysosomal storage disease; mutation on chromosome 15; hexosaminidase A severely deficient

Clinical manifestations: motor incoordination, lethargy, muscle flaccidity, high cognitive impairement, "cherry red spot" appears on retina

Epidemiology: 1 in 30 carrier rate in Ashkenazi Jews

Pathophysiology: accumulation of ganglioside causes progressive destruction of neurons and brain cells

Diagnosis: genetic testing, "cherry red spot" on retina on ophthalmological exam

Prognosis: death occurs at age 3

2. Neurofibromatosis

Etiology: autosomal dominant; NF1-mutation in NF1 gene which is tumor suppressor gene coding for neurofibromin in chromosome 17; NF2-mutation in NF2 gene which is tumor suppressor gene coding for merlin

Clinical manifestations: 6 or more cafe-au-lait spots, axillary or inguinal freckles, neurofibromas, optic nerve tumor, iris tumors, long bone abnormalities

Epidemiology: NF1- 1 in 3,000 (more common); NF2- 1 in 37,000

Pathophysiology: NF1- decreased production of neurofibromin results in various clinical manifestations; NF2- decreased production of merlin results in predisposition to develop tumors of CNS and PNS

Diagnosis: first degree relative with NF1, genetic testing, CT, MRI, neurological evaluation, acoustic and ophthalmological exams

Prognosis: NF1- reduces life expectancy by 15 years; NF2-surgery may improve life expectancy to 15 years

3. Parkinson's Disease is a progressive neurodegenerative

condition caused by insufficient quantities of the neurotransmitter Dopamine in the brain, this deficiency causes motor and non-motor symptoms.

Pathophysiology:

Parkinson disease is caused by the progressive impairment or deterioration of neurons (nerve cells) in an area of the brain.

• Neurons produce a vital brain chemical known as dopamine

• Dopamine serves as a chemical messenger allowing communication between areas of the brain.

• A lack of dopamine results in abnormal nerve functioning, causing a loss in the ability to control body movements.

Clinical manifestations :-

- stopping posture

- blinking of eyes

- tremor

- bradycardia

- rigidity

- micrographia

- masked facial expression

4. Cri-du-chat syndrome

congenital microdeletion of short arm of chromosome 5

-findings: microcephaly, moderate to severe intellectual diability, high pitch crying and mewing, cardiac issues.