Neurofibromatosis Type 1: Diagnosing Criteria

00:01 These are all genetic conditions and we're going to learn about the genetics of NF1 and NF2.

00:06 First, we'll focus on NF1.

00:08 NF1 results from a mutation in the NF1 gene.

00:12 The NF1 gene encodes a protein called neurofibromin, which you see here.

00:16 And neurofibromin is a break.

00:18 It is a tumor suppressor, it slows down growth.

00:21 And when it's normally functioning in the cell, the RAS pathway, which is the most common cell proliferation pathway is slowed down.

00:29 RAS cannot cause the cells to grow.

00:32 When you lose neurofibromin, cell growth is uninhibited and cells are able to grow.

00:38 And one of those cell growth signals is MEK.

00:40 And we're going to come back to this at the end of the lecture when we talk about treatment.

00:44 But that's an important downstream protein that causes cells to grow and proliferate and contributes to tumor formation in neurofibromatosis type 1.

00:55 So how do we diagnose patients within NF1? Well, it's a genetic condition, but we actually often don't test the genes.

01:02 We can...

01:03 we can look for that specific mutation in the NF1 gene that's causing this condition.

01:07 But as I said, it's one of the most, it's one of the biggest genes in the human body.

01:12 And it's very difficult to test all of the mutations that may occur.

01:16 So primarily, we rely on a clinical diagnosis.

01:19 And there are seven features that I want you to think about when making a clinical diagnosis of NF1.

01:25 The first are Cafe-au-lait macules.

01:27 And we saw those in an image and we'll look at a few more.

01:30 And six or more cafe-au-lait macules is sufficient to make a diagnosis or part of a diagnosis of NF1.

01:36 In prepubertal individuals, those must be greater than five millimeters and postpubertal individuals greater than 15 millimeters.

01:44 The second criterion are neurofibromas.

01:47 And we also looked at those for our patient.

01:49 Those are the lesions that we see out on the skin, the bumps.

01:52 And two or more dermal neurofibromas or one plexiform neurofibroma is sufficient for a major criteria for diagnosing neurofibromatosis.

02:01 We'll look at axillary and inguinal freckling or skinfold freckling, which is also one of the seven criteria.

02:07 Optic pathway gliomas.

02:09 Lisch nodules, which was present in our patient in case.

02:12 Osseous abnormalities.

02:14 We'll talk about sphenoid winged dysplasia, and pseudarthrosis.

02:18 And a family history.

02:20 Patients must have two of these seven criteria to be clinically diagnosed with NF1.

02:27 There are also additional symptoms and signs that we can see in these patients.

02:30 That aren't sufficient to establish a diagnosis, but can be highly contributing to the evaluation and management of these patients.

02:39 Cardiovascular malformations can occur.

02:40 We think of coarctation of the aorta or renal artery stenosis, which can occur later in life or in adolescent individuals.

02:47 Learning disabilities are extremely common in these patients and occur in up to 75% of this group of patients.

02:54 ADHD, Attention Deficit Disorder, as well as Hyperactivity Activity Disorder is also common.

03:00 Osteoporosis in Peenya, thinning of the bones, pectus excavatum, which is invagination of the sternum.

03:07 Bony abnormality that can occur.

03:09 Pheochromocytoma is another tumor that occurs on the adrenal glands and can cause elevated high blood pressure in these patients.

03:16 Glomus tumors on the skin or under the nails.

03:19 Gastrointestinal stromal tumors those are called GIST tumors, neat tumors that occur in the GI tract and are uncommon but can be seen in NF1.

03:28 Juvenile myelomonocytic leukemia, which is a very difficult to complication of this condition.

03:33 It's rare, but can occur in young adolescents.

03:36 Dural ectasia, scoliosis, and early onset breast cancer.

03:40 So almost all organ system can be involved in NF1.

03:44 And we're going to focus on those that establish the diagnosis and other principal organs to be affected.