is the gene involved in inherited neurofibromatosis types I.
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 16-year-old boy comes to the clinic because of the appearance of several "lumps" all over his body for the past year. He states that they have progressively appeared and growth, are not painful, and none have gone away. Family history is significant for the development of similar symptoms in his father and uncle while in their teens. His temperature is 37.0°C (98.6°F), pulse is 72/min, respirations are 18/min, and blood pressure is 126/73 mm Hg. Physical examination shows numerous small cutaneous tumors all over his body and pigmented hamartomas on each iris. He also has hyperpigmented macules of varying sizes on his back and axillary areas. Which of the following is the most likely diagnosis of the cutaneous lesions?
With neurofibromatoses, neuro refers to the nerves, fibro- refers to fibrous tissue, and -oma means growth, or tumor.
The body’s central nervous system is made up of the brain and the spinal cord, which are surrounded by three protective layers called the meninges.
Part of the central nervous system are the cranial nerves, which originate in the brainstem and innervate the head and neck, and the spinal nerves, which originate in the spinal cord, and supply the rest of the body.
Each nerve is surrounded by a nerve sheath, which is produced by cells called fibroblasts.
Inside, each nerve there are several fascicles, and each fascicle, in turn, is made up of several axons.
The axons are the long projections of neurons, that carry the information as electrical signals running up and down their length.
Along the axon there are cells called Schwann cells, which produce a myelin cover for the axon.
The myelin helps electrical signals travel along the axon faster.
Now, neurofibromatoses are genetic diseases which cause non-cancerous growths to form in the body’s nerve tissue, and there are two types - type I and type II.
They’re caused by inheriting faulty copies of either the NF1 or NF2 gene, which are found on chromosomes 17 and 22, respectively.
Just remember, NF1 goes with chromosome 17 and NF2 goes with chromosome 22.
Both of these have an autosomal dominant inheritance pattern, so a child only needs one faulty copy from either parent to get the disease.
Normally, these are tumor suppressor genes, which means they stop cells from dividing uncontrollably.
So when there’s a mutation in the gene, it leads to uncontrolled growth of fibromas which are growths that have multiple cell types including neurons, Schwann cells, and other supporting connective tissue.
Neurofibromatosis type I, is also called von Recklinghausen’s syndrome typically affects the nerves in the extremities and the skin.
It causes lots of neurofibromas, which are benign tumors that grow from the nerve sheath and are made of a mixture of Schwann cells, fibroblasts, and immune cells.Usually, they grow just beneath the skin surface, but they can also grow along peripheral and spinal nerves.
Cutaneous neurofibromas typically start forming in childhood and increase in number over time. They appear as a painless, mobile lumps under the skin.
On top of that, people with type I neurofibromatosis often have skin markings called café-au-lait spots, which are flat patches that are the color of milky coffee.
These spots typically appear on the back, the buttocks, and the thighs in the first year of life, and increase in number over time.
Also, on an eye exam, there are small tan colored bumps called Lisch nodules can be seen on the iris.
These nodules almost always appear by the age of 6, but don’t usually cause any sight problems.