136: Tuberous Sclerosis Flashcards
What are the common clinical presentations of Tuberous Sclerosis Complex (TSC)?
TSC commonly presents with seizures during infancy and is associated with neuropsychiatric disorders (TAND) that affect cognitive, behavioral, and psychiatric functions.
What is the role of TSC1 and TSC2 in Tuberous Sclerosis Complex?
TSC1 (Hamartin) and TSC2 (Tuberin) are tumor suppressor genes that inhibit growth signaling through the mTORC1 pathway. Inactivating mutations in these genes lead to increased mTORC1 signaling and cell growth.
What are the cutaneous findings associated with Tuberous Sclerosis Complex?
The primary cutaneous finding in TSC is hypomelanotic macules, which are present in over 90% of children at birth or within the first few years of life. These may fade or disappear in adulthood, and detection can be improved with Wood’s lamp or UV light.
What are some worse risk factors associated with Tuberous Sclerosis Complex?
Worse risk factors for TSC include: TSC2 subtype, PKD2-TSC deletion leading to polycystic kidney disease, high tuber count and early onset epilepsy, skin manifestations such as angiofibromas and shagreen patches, and UV exposure.
What is the likely neuropsychiatric condition in a TSC patient with seizures and behavioral difficulties?
The likely condition is TSC-associated neuropsychiatric disorders (TAND), which affect approximately half of patients with TSC.
What are the risk factors for severe outcomes in a TSC patient with seizures and intellectual impairment?
Risk factors for severe outcomes include high tuber count, early-onset epilepsy, and TSC2 subtype.
What gene mutations are associated with Tuberous Sclerosis Complex (TSC)?
Mutations in the TSC1 or TSC2 tumor suppressor genes.
What are common clinical presentations of Tuberous Sclerosis Complex during infancy?
Seizures are commonly presented during infancy.
What is the transmission pattern of Tuberous Sclerosis Complex?
Sporadic cases are more common (2/3) compared to hereditary cases (1/3).
What is the role of the TSC1 and TSC2 genes in cell growth?
They form a complex that inhibits growth signaling through the mTORC1 pathway.
What are some skin manifestations associated with Tuberous Sclerosis Complex?
Angiofibromas, shagreen patches, and fibrous forehead plaques.
What is the significance of hypomelanotic macules in Tuberous Sclerosis Complex?
They are present in over 90% of children with TSC and can be detected using Wood’s lamp or UV light.
What is the clinical significance of TSC-associated neuropsychiatric disorders (TAND)?
They involve difficulties related to cognitive, behavioral, and psychiatric disorders.
What are the two types of skin lesions associated with Tuberous Sclerosis Complex (TSC)?
- Ash-leaf spots: Solitary to multiple, 0.5 to 3.0 cm in diameter, off-white and incompletely depigmented oval macules, commonly seen on the trunk and buttocks; can cause poliosis when located on the scalp.
- Confetti skin lesions: Multiple hypopigmented macules, 2-3 mm, typically occurring on the legs below the knees or forearms.
What is the major criterion for diagnosing hypopigmented macules in TSC?
> 3 hypopigmented macules measuring > 5 mm in longest dimension.
What percentage of patients with TSC develop facial angiofibromas, and at what age do they typically appear?
75-90% of patients develop facial angiofibromas, which typically appear between 2-5 years of age.
Describe the characteristics of facial angiofibromas in TSC.
Facial angiofibromas are solitary to multiple, 1-3 mm pink to red papules with a smooth surface occurring on the central face, particularly concentrated on the alar grooves, cheeks, nose, and chin, with relative sparing of the upper lip and lateral face. They may increase in size and number during puberty and tend to be stable in size in adulthood.
What is a fibrous cephalic plaque and its prevalence in TSC patients?
A fibrous cephalic plaque is an irregular, soft to firm connective tissue nevus that may be congenital or develop gradually over years, occurring in 40% of patients. It typically develops on the forehead but can also occur on the scalp, cheeks, and face.
What is a shagreen patch and its common locations in TSC patients?
A shagreen patch is a 1-10 cm firm or rubbery irregular plaque with coalescing papules and nodules, creating a bumpy or orange skin appearance. It is most commonly seen on the lower back to sacral region, and less commonly on the mid/upper back, buttocks, or thighs.
What are ungual fibromas and their prevalence in adults with TSC?
Ungual fibromas, also known as Koenen tumors, are common in 85% of adults with TSC, primarily found on the toes more than the fingers.
What are periungual fibromas and their characteristics?
Periungual fibromas are red firm, pointed, hyperkeratotic or soft and round papules/nodules that arise in the proximal nail fold and can press on the nail matrix, causing a longitudinal groove.
What is the typical appearance and diagnostic significance of a Shagreen patch?
A Shagreen patch is a firm or rubbery irregular plaque with coalescing papules and nodules, creating a bumpy or orange skin appearance. It is a major diagnostic feature of TSC.
What is the typical location and diagnostic significance of a fibrous cephalic plaque?
A fibrous cephalic plaque is typically located on the forehead and is a major diagnostic feature of TSC.
How can hypomelanotic macules be better visualized?
Hypomelanotic macules can be better visualized using a Wood’s lamp or UV light.
What are Ash-leaf spots and where are they commonly found?
Ash-leaf spots are solitary to multiple hypomelanotic macules 0.5 to 3.0 cm in diameter, typically found on the trunk and buttocks, and can cause poliosis when located on the scalp.
What is the major criterion for diagnosing hypopigmented macules?
> 3 hypopigmented macules measuring > 5mm in longest dimension.
At what age do facial angiofibromas typically appear?
Facial angiofibromas appear between 2-5 years of age in 75-90% of patients.
What are the characteristics of fibrous cephalic plaques?
Fibrous cephalic plaques are irregular, soft to firm connective tissue nevi that may be congenital or develop gradually, typically found on the forehead.
What is a shagreen patch and where is it commonly located?
A shagreen patch is a 1-10 cm firm or rubbery irregular plaque with coalescing papules, commonly seen on the lower back to sacral region.
What percentage of adults with TSC have ungual fibromas, and where are they most commonly found?
85% of adults with TSC have ungual fibromas, which are more common on the toes than on the fingers.
What are periungual fibromas and what effect do they have on the nail matrix?
Periungual fibromas are red firm, pointed, hyperkeratotic or soft and round papules/nodules that arise in the proximal nail fold and can press on the nail matrix causing a longitudinal groove.
What are the major and minor criteria for diagnosing ungual fibromas in Tuberous Sclerosis Complex (TSC)?
Major criterion: > 2 ungual fibromas
Minor criterion: Not specified in the text.
What is dental pitting and how is it identified in TSC patients?
Dental pitting refers to multiple pits (tiny pinpoint or large crater-like lesions) in the enamel, observed in 100% of TSC patients. Identification is enhanced using a dental plaque stain.
What are the characteristics and common sites of intraoral fibromas in TSC patients?
Intraoral fibromas occur in 50% of TSC patients, more commonly in adulthood. The most common site is the gingivae, but they can also appear on the buccal, labial mucosa, hard palate, and tongue. Some patients may experience diffuse gingival overgrowth.
What are some non-cutaneous findings associated with Tuberous Sclerosis Complex (TSC)?
Non-cutaneous findings include: Brain: Cortical dysplasia, subependymal nodules, and subependymal giant cell astrocytomas. Seizures: Occur in 80% of patients, often starting in the first 3 years of life, with treatment options including Vigabatrin and epilepsy surgery. TAND: Behavioral, intellectual, and psychosocial difficulties, with a high prevalence of Autism spectrum disorder, ADHD, and anxiety disorders.
How can dental pits be identified and what is their diagnostic significance?
Dental pits can be identified using a dental plaque stain. They are a minor diagnostic criterion for TSC if more than three pits are present.
What are the alternative treatment options for TSC patients with seizures that are intractable to anticonvulsant therapy?
Alternative treatments include epilepsy surgery, ketogenic diet, vagus nerve stimulation, and mTOR inhibitors.
What is the prevalence of autism spectrum disorder and ADHD in TSC?
Nearly half of patients with TSC will have autism spectrum disorder and ADHD.
What is the treatment of choice for infantile spasms in TSC?
Vigabatrin is the treatment of choice for infantile spasms.
What percentage of TSC patients experience seizures?
Approximately 80% of TSC patients experience seizures.
What are some behavioral issues associated with TSC?
Behavioral issues can include Autism spectrum disorder, ADHD, and anxiety disorders.
What is pachydermodactyly?
Pachydermodactyly is a benign thickening of the proximal fingers.
What are miliary fibromas?
Miliary fibromas are patches of multiple minute papules usually on the neck or trunk that appear like ‘goose-flesh’.
What is the prevalence of subependymal nodules in individuals with Tuberous Sclerosis Complex (TSC)?
Subependymal nodules are present in 80% of individuals with TSC.
What is the common treatment for cardiac rhabdomyomas in TSC patients?
The common treatment for cardiac rhabdomyomas is mTOR inhibitors, which help speed regression.
What percentage of TSC patients are affected by angiomyolipomas, and what is the typical treatment approach?
Angiomyolipomas affect 80% of TSC patients. The treatment approach includes selective embolization followed by corticosteroids for acute hemorrhage, and mTOR inhibitors for asymptomatic growing angiomyolipomas.
What are the common respiratory complications associated with lymphangioleiomyomatosis (LAM) in TSC?
Common respiratory complications of LAM include spontaneous pneumothorax, cyclothorax, dyspnea, cough, and hemoptysis.
What is the most common type of retinal hamartoma found in TSC patients?
The most common type of retinal hamartoma in TSC patients is flat and translucent lesions, while others may be elevated, opaque, or calcified.
What are the potential complications of renal lesions in TSC?
Renal lesions in TSC can lead to renal insufficiency, hypertension, and retroperitoneal hemorrhage.
What is the risk of developing renal cell carcinoma in TSC patients?
The risk of developing renal cell carcinoma in TSC patients is approximately 2-3%.
What are the characteristics of retinal achromic patches in TSC?
Retinal achromic patches in TSC are characterized as hypopigmented patches in the retina.
What is the likely diagnosis and treatment for a TSC patient with dyspnea and spontaneous pneumothorax?
The likely diagnosis is lymphangioleiomyomatosis (LAM), which is common in adult females with TSC. Treatment includes mTOR inhibitors for patients with moderate to severe lung disease or rapid progression.
What is the typical course and management for cardiac rhabdomyomas in TSC?
Cardiac rhabdomyomas in TSC are often asymptomatic and spontaneously regress. If symptomatic, mTOR inhibitors can be used to speed regression.
What is the first-line treatment for renal angiomyolipomas with acute hemorrhage?
The first-line treatment for renal angiomyolipomas with acute hemorrhage is selective embolization followed by corticosteroids.
