Development Regression, Neurocutaneous Disorders and Tuberous Sclerosis

00:01 Developmental regression: Loss of previously attained developmental milestone.

00:06 So we’re going back from that milestone, back towards a primitive type of behavior.

00:11 Almost always has a bad prognosis, keep that in mind.

00:15 Onset age, before 2.

00:18 Here, you might be thinking about mitochondrial disorders including your mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms.

00:27 Hypothyroidism, cretinism.

00:30 Neurocutaneous disorders such as neurofibromatoses.

00:34 And gray matter disorder.

00:35 Remember, bad prognosis.

00:37 Onset before age of two.

00:39 White matter disorder, metachromatic leukodystrophy.

00:43 Amino acid metabolism such as PKU or phenylketonuria.

00:47 And enzymatic disorders.

00:49 These are developmental regression.

00:52 Clinical pearl, bad prognosis, here, referring to those differentials before the age of 2.

01:00 The neurocutaneous disorders that we’ll walk through quickly.

01:03 It’s called tuberous sclerosis complex.

01:06 Not tuberculosis, but tuberous sclerosis.

01:09 This is an inherited, hereditary issue.

01:13 Neurofibromatosis, specially we have neurofibromatosis type 1, which is known as your neurofibromin protein or neurofibromin 1 protein.

01:23 And with this, you’ve heard of Café au lait spots and so on and so forth.

01:28 Sturge-Weber.

01:29 In vascular pathology, with Sturge-Weber, you’ve talked about port wine syndrome.

01:35 Remember with Sturge-Weber, it’s a problem with the leptomeningeal blood vessels, and therefore may result in new onset seizure in this patient.

01:43 Familial telangiectasia or you’ve heard of hereditary, hemorrhagic telangiectasia, Osler–Weber–Rendu.

01:51 Von Hippel-Lindau disease.

01:52 Remember with Von Hippel-Lindau disease, you could have bilateral renal cell carcinoma in a very young patient.

02:00 Along with this, there could be hemangioblastomas of the cerebellum and the retina.

02:05 And we have incontinentia pigmenti.

02:08 And ataxia telangiectasia.

02:12 Let’s talk about tuberous sclerosis.

02:14 Autosomal dominant disorder To begin with, please understand that this has nothing to do with an infection.

02:21 Incidence: 1 in 10,000.

02:23 There are two gene loci.

02:25 You have TSC1 on chromosome 9.

02:28 Please memorize hamartin.

02:31 Now, with hamartin, you can play with that a little bit more and this is what I recommended to do.

02:36 You’ve heard of, in pathology, hamartomas and hamartoma would mean increased proliferation of cell, but completely, completely, non-neoplastic by definition.

02:47 With tuberous sclerosis, there are important hamartomas that may be seen.

02:53 And one of these hamartoma could be seen, well, perhaps in the heart.

02:57 What I’m saying is hamartin chromosome 9, at least know TSC1.

03:04 TSC2, T as in two and use that to your advantage with the gene tuberin, T.

03:13 At least know hamartin with TSC1 at this juncture.

03:18 The classic Vogt triad of syndrome include the skin lesions.

03:23 Our topic is under neurocutaneous and skin lesions include something like your ash-leaf spots, shagreen spots.

03:31 There might be convulsions and these are your tubers that you might find in the brain and there might be intellectual disability.

03:39 With tuberous sclerosis, things that you’re paying attention to, the primary symptoms cluster.

03:45 Remember that skin? In the skin, it’s called adenoma sebaceum, ungual fibroma, cortical tubers.

03:52 Those tubers will be found in the brain.

03:54 And we have subependymal nodules and multiple retinal astrocytomas.

04:01 The secondary symptoms: Infantile spasms.

04:04 The ash-leaf spot, as the name implies, will be white and it’s hypomelanotic macule.

04:13 And of course, that’s referring to blanch – I shouldn’t use the word blanch, but we’ll say pale and it would be hypopigmented.

04:23 In the heart, we have these rhabdomyomas.

04:26 Remember, in the heart, in cardiology, very rare that you might have a cancer in the heart.

04:33 However, if by chance you think of a benign tumor that might be located in it, and it’s a rhabdomyoma, then please know that this could be part of tuberous sclerosis, which is my topic.

04:45 Renal angiolipoma in the kidney.

04:48 And first degree relative with tuberous sclerosis complex or TSC.

04:54 And keep in mind once again, at least know TSC1, which then represents hamartin.

04:59 There is no condition that we see here, either primary or secondary, in terms of symptom that truly would be malignant, is there? No.