Approach to neurocutaneous syndromes: Clinical sciences

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Introduction 0:00–0:36

Neurocutaneous syndromes are a heterogeneous group of genetic disorders that affect both the skin and the nervous system.
Although several neurocutaneous syndromes present with manifestations during infancy and childhood, some are not usually diagnosed until adolescence or early adulthood.
The most common neurocutaneous syndromes with childhood onset can be differentiated on the basis of skin lesion morphology.
Now, if a pediatric patient presents with a chief concern suggesting a neurocutaneous syndrome, you should first obtain a focused history and physical examination history, commonly reveals delayed motor skills, cognitive deficits and neurologic symptoms such as weakness.

Focused H&P 0:36–1:18

Additionally, the family history might be positive for a neurocutaneous syndrome. The physical exam typically reveals focal neurologic findings and cutaneous lesions.
With these findings consider the possibility of a neurocutaneous syndrome and then assess the morphology of your patient's skin lesions.
Let's take a look at our first skin lesion. If you identify multiple brown macules known as cafe oet spots, cafe Oula macules or calms, consider neurofibromatosis type one, also known as NF one or Von Recklinghausen disease.

Café-au-lait macules 1:18–5:34

This autosomal dominant condition is caused by mutations of the NF one gene on chromosome 17. These patients often have a family history of NF one in a first degree relative.
Many present with symptoms of neurocognitive dysfunction such as developmental delay, attention deficit hyperactivity disorder or a learning disability.
Meanwhile, the exam typically reveals multiple cafe ole macules, skin fold freckling, especially in the axilla or inguinal regions and neurofibromas which are benign peripheral nerve sheath tumors.
During early childhood, you'll typically see plexiform neurofibromas which are irregular diffuse and poorly defined and involve multiple nerve fascicles.
In late childhood or adolescence, patients may develop dermal fibromas which are small growths just under or above the skin.
These findings are suggestive of NF one but to confirm the diagnosis, you'll also need to look for noncutaneous manifestations to do so, perform an ophthalmologic examination, order skeletal x rays and consider an MRI of the brain.
Then assess NF one, diagnostic criteria criteria for NF one includes six or more cafe ole macules larger than five millimeters before puberty or larger than 15 millimeters.
After puberty, skin fold, freckling in the axillary or inguinal region, two or more dermal neurofibromas or one plexiform neurofibroma and characteristic skeletal dysplasia, such as sphenoid wing dysplasia.
Other criteria include optic gliomas, lych nodules which are pigmented dome shaped iris, hematomas, an affected first degree relative or Noonan syndrome, which is a genetic disorder associated with characteristic, facial features, short stature, heart defects and developmental delay if your patient meets at least two of these criteria.
Diagnose NF one, here's a clinical pearl isolated CALS often occur without underlying pathology, but multiple CALS can be associated with other conditions such as mccune Albright syndrome.
However, in mccune Albright syndrome, cafe huet macules have borders with an irregular coast of Maine appearance and are often isolated to one side of the body.
On the flip side. In neurofibromatosis, cafe, Oula macules have smooth borders resembling the coast of California.
Let's follow that up with a high yield fact, neurofibromatosis type two and schwannomatosis are less common forms of neurofibromatosis that usually present during late adolescence or adulthood.
Neurofibromatosis type two is inherited in an autosomal dominant fashion and is characterized by cutaneous plaques, nodules, meningiomas, cataracts and bilateral vestibular or acoustic schwannomas which can cause sensory neural hearing loss.
On the other hand, schwannomatosis is a distinct form of neurofibromatosis characterized by multiple Schwannomas that affect the peripheral nervous system and spare the vestibular system.
Now, let's switch gears and discuss patients with hypopigmented macules. This finding should make you consider tuberous sclerosis complex or TSC, an autosomal dominant condition caused by mutations in the tumor suppressor TSC genes on chromosome nine or 16 manifestations of TSC are heterogenous and include skin and brain lesions as well as abnormal growths involving the eyes, kidneys and heart.

Hypopigmented macules5:34–8:50

The family history commonly reveals a first degree relative with TSC and affected Children often have intellectual disabilities or autism spectrum disorder.
Many infants with TSC present during infancy with intractable seizures, especially infantile spasms. As for the skin exam, you'll typically see characteristic lancet hypomelanotic macules also called ash leaf spots which are best visualized under a woods lamp.
Additionally, you might notice shagreen patches which are raised lesions with an orange peel texture that are often found in the lumbosacral region.
Some Children develop facial angiofibromas on the nose and cheeks that mimic acne or raised yellow, brown or flesh colored collagen plaques on the forehead.
If your patient is an adolescent, you may notice periungual fibromas or small skin nodules under or around the fingernails or toenails.
Since these findings are highly suggestive of TSC, you should also perform an ophthalmologic examination and order skeletal x-rays, an MRI of the brain and cardiac and renal ultrasounds to look for noncutaneous manifestations of TSC, then assess the TSC clinical diagnostic criteria.
Major criteria include three or more hypomelanotic macules, three or more angiofibromas, ual fibromas and chagrin patches, noncutaneous major criteria.
You might see on imaging include cardiac rhabdomyomas, pulmonary lymphangioleiomyomatosis, angiomyolipomas, and retinal hamartomas as well as brain lesions such as cortical dysplasia, subependymal nodules and subependymal giant cell astrocytomas.
Minor criteria include confetti skin lesions, dental enamel pits, intraoral fibromas, retinal achromic patches, multiple renal cysts and nonrenal hamartomas.
If your patient meets two major criteria or one major plus at least two minor criteria, diagnose tuberous sclerosis complex.
Now, let's discuss patients with a facial port wine stain, which also goes by the name nevus flammeus whenever you see this congenital capillary malformation.

Port-wine stain 8:50–11:01

Consider sturge Weber syndrome. Here is another clinical pearl in the newborn period.
Nevus flammeus can be mistaken for nevus simplex. A common benign congenital capillary malformation that is affectionately called a stork bite or angel kiss.
Unlike nevus flammeus, nevus simplex is usually found on the glabella eyelids or nape of the neck. It blanches with pressure and becomes more prominent with crying.
In contrast, nevus flammeus is often associated with Sturge Weber syndrome, especially when it's located on the upper eyelid and forehead in the distribution of the first or second division of the trigeminal nerve.
Now, Sturge Weber has a heterogenous presentation and affected patients often have a history of seizures, transient stroke like episodes and glaucoma.
Later in childhood, these patients often develop intellectual and learning disabilities. The exam typically demonstrates a facial port wine stain.
And in some cases, you may see hemiparesis to evaluate further order. An MRI of the brain imaging typically reveals subcortical laminar calcifications due to leptomeningeal angiomatosis and white matter abnormalities, IPs so lateral to the facial port wine stain which confirms the diagnosis of Sturge Weber syndrome.
Here's another clinical Pearl intracranial involvement places patients with sturge Weber at risk of hypopituitarism. So be sure to monitor your patient's growth, also monitor levels of TSH and free T four growth hormone ACTH and gonadotropic hormones like FSH and LH.
Finally, if the exam reveals oculocutaneous telangiectasias, consider ataxia telangiectasia, which is also known as at or Louis Barre Syndrome.

Telangiectasia 11:01–13:28

At is an autosomal recessive neurodegenerative disorder caused by mutations in the ATM gene on chromosome 11 Q 2223. So, in some cases, the family history is positive.
This mutation impairs the cell's ability to effectively repair damaged double stranded DNA, which ultimately impacts immune function.
Consequently, patients often experience recurrent sinopulmonary infections and malignancies such as acute lymphocytic leukemia and lymphoma.
Many patients present with developmental delay and progressive ataxia which eventually leads to loss of ambulatory function.
The exam often reveals oculocutaneous telangiectasia and occasionally telangiectasias of the nasal bridge and ears. You're also likely to notice truncal ataxia and oculomotor apraxia, which is the inability to coordinate head and eye movements while shifting gaze rapidly to evaluate further order labs and imaging.
This includes a CBC serum immunoglobulins and alpha fetoprotein and obtain an MRI of the brain. The labs might demonstrate decreased lymphocyte and immunoglobulin levels and elevated alpha fetoprotein levels.
While the MRI shows cerebellar atrophy, these results are highly suggestive of ataxia telangiectasia and you can confirm the diagnosis with genetic testing.
Here is your last clinical Pearl Von Hippel Lindau syndrome is an autosomal dominant neurocutaneous disorder that usually presents during early adulthood.
This syndrome is caused by mutations of the VHL gene on chromosome three and is associated with multiple tumors such as pheochromocytoma, brain or spinal hemangioblastoma, pancreatic neuroendocrine tumors and renal cysts or carcinoma.
All right, as a quick recap neurocutaneous syndromes that present during childhood can be differentiated based on skin lesion morphology.

Review13:28–14:16

Patients with cafe Oula macules who meet diagnostic criteria have NF one while those with hypopigmented macules who meet diagnostic criteria have TSC if your patient has a facial port wine stain and neuroimaging reveals leptomeningeal angiomatosis diagnose sturge Weber syndrome.
Finally, the combination of oculocutaneous telangiectasia, immunosuppression, ataxia, elevated alpha fetoprotein levels and cerebellar atrophy suggests ataxia telangiectasia.
Approach to neurocutaneous syndromes: Video, Steps | Osmosis