Case: 21-year-old Man with Pain

00:01 In this lecture, we're going to talk about Inherited Tumor Syndromes.

00:05 This is one of my favorite topics in neurology.

00:07 I'm really excited for you to learn this.

00:09 It is complicated and complex.

00:11 These patients are rare, but we see them in neurology, and I want you to understand how to diagnose, monitor, and treat some of these patients.

00:21 Let's start with a case.

00:23 So 21-year-old man who presented with pain.

00:26 He presented to the clinic with increasing pain, limiting activities of daily living.

00:31 Since birth, he has had multiple birthmarks over his body.

00:34 More than six.

00:36 And at puberty, he began to develop small bumps on his skin.

00:40 He was subsequently confirmed to have Lisch nodules.

00:43 Those are iris hamartomas.

00:46 Bumps and spots on the eyes that were evaluated by an eye doctor.

00:51 By the age of 19, he developed progressive pain in the neck, bilateral upper extremities, head, abdomen, pelvis, and at the sites of his cutaneous lesions.

01:00 So what's the diagnosis? Well, there's a few clinical features that we should see in this case.

01:06 The first is this patient has multiple birthmarks.

01:09 They sound hyperpigmented, like dark spots, and they may be cafe-au-lait macules.

01:15 So we want to be thinking about an inherited syndrome.

01:18 The second he has multiple bumps on the skin that are suggestive of neurofibromas.

01:24 So we may be thinking about a tumor condition that results in increased risk or presence of tumors of the nerves.

01:32 And this sounds like a genetic disorder.

01:34 It's been there his entire life.

01:36 So let's look at some of the characteristic findings in our patient.

01:40 Here on the left, we see a skin finding.

01:43 This is this birthmark.

01:44 This well circumscribed, sharply, demarcated lesion, you can draw a line around it.

01:50 It's hyperpigmented.

01:51 And this is the appearance of a cafe-au-lait macule.

01:55 On the right, we see these bumps, the bumps on the skin.

01:58 They're out on the surface.

01:59 Some may be a little bit deeper than in the surface, and there are multiple, all over the arms and legs in this patient.

02:06 And they have the appearance of a neurofibroma.

02:10 So what's the diagnosis? Is this NF1, NF2, schwannomatosis, or tuberous sclerosis? Well tuberous sclerosis, as we'll learn is a condition that often presents with seizures, brain findings, and kidney tumors.

02:24 We don't hear of any of those things in this patient.

02:26 This patient has cutaneous lesions.

02:29 This doesn't sound like a diagnosis of TSC.

02:33 Schwannomatosis.

02:34 This is a condition that is rare, really rare.

02:37 And often presents with pain.

02:39 Our patient has pain, but a lot of skin findings that we don't typically see in schwannomatosis.

02:45 So we don't like a diagnosis of schwannomatosis.

02:49 What about NF2? NF2 is an inherited condition.

02:53 It starts at the beginning of life, but typically presents with hearing loss from bilateral vestibular schwannomas.

03:00 And this patient does not have hearing loss.

03:03 This is the classic presentation of adult onset NF1.

03:08 A very typical presentation of a patient with cutaneous lesions and peripheral nerve lesions that are suggestive of this NF1 diagnosis.

03:18 So in this lecture, we're going to think about some of these inherited tumor syndromes.

03:22 We're going to learn about neurofibromatosis type 1, we're going to learn about neurofibromatosis type 2, and we're going to learn about tuberous sclerosis.

03:31 These are genetic conditions.

03:33 This is a group of autosomal dominant inherited conditions that are characterized by abnormalities in a tumor suppressor gene.

03:41 And that abnormality leads to tumor growth.

03:43 And primarily, we see tumors of the nerves.

03:46 When you think about these three conditions, I want you to think of them as tumor suppressor syndromes.

03:52 And when you think about tumor suppressor syndromes, I want you to think about these three diagnoses.

03:57 NF1, NF2, and tuberous sclerosis.

04:03 This group of conditions falls into a family of disorders that we call, the phakomatoses.

04:09 They are neurogenetic conditions.

04:11 They are neurologic manifestations, and they are genetic conditions.

04:15 We also call them neurocutaneous syndromes because there's neurologic involvement, and cutaneous findings.

04:22 This group we call the phakomatoses includes a lot of disorders.

04:26 Tuberous sclerosis we're going to learn about but other conditions includes Sturge-Weber, Von Hippel Lindau, and Ataxia-telangiectasia.

04:34 In the next part of this talk, I want to focus on neurofibromatosis.

04:39 We're going to talk about NF1, we're going to talk about NF2.

04:42 and I'll mention schwannomatosis.

04:44 Of these conditions NF1 is the most common, and we should spend the most time learning about that.

04:50 NF2 is important.

04:52 It can result in significant manifestations and morbidity from patients that have that disease, and we should also know about that.

05:00 Schwannomatosis is quite rare.

05:02 And I want you to know that it looks a lot like NF2.

05:05 But patients don't have brain tumors and they don't have brain findings.

05:09 And they really commonly present with pain.

05:11 So we don't spend a lot of time talking about schwannomatosis.