Edit concept Question Editor Create issue ticket

Tuberous Sclerosis

TS

Tuberous sclerosis, otherwise referred to as Bourneville's disease or tuberous sclerosis complex, is an inherited disease that affects multiple systems. It is an uncommon condition, which leads to the formation of many tumors in various locations of the body, which are non-malignant.

Tuberous Sclerosis - Symptom Checker

Ad Check possible symptoms of Tuberous Sclerosis now!

Presentation

Tuberin and hamartin, the two proteins related to the inhibition of cellular growth and differentiation are responsible for mediating these processes in the entire body. Their failure to serve their purpose practically implies that tumors, benign in nature, are allowed to develop nearly everywhere throughout the body. A defined set of diagnostic criteria have been established by the Diagnostic Criteria Committee of the National Tuberous Sclerosis Association (USA) [4].

Patients affected by tuberous sclerosis may present with the following tumors and symptoms:

  • Skin: Patients may present with facial angiofibromas [5], ash-leaf spots, confetti lesions, shagreen patches, fibrous plaques, and periungual fibromas.
  • Heart: Rhabdomyomas are the type of tumor that most commonly forms.
  • Brain: The brain constitutes on of the most common locations for the generation of tumors. Histologically, both glial and neuronal cells are observed within the lesion and myelination is considerably affected. It is believed that, in some cases, a greater number of cortical tubers (brain tumors) is associated with severer epileptic manifestations. SEN (subependymal nodules) and SEGA (subependymal giant cell astrocytomas) tumors are also a manifestation of tuberous sclerosis: SEN lesions are the first to appear and, under some circumstances, lead to the development of SEGA tumors, which form in the foramen of Monro and might lead to hydrocephalus.
  • Kidneys: Angiomyolipomas, cystic lesions. Angiomyolipomas are constituted of blood vessels, adipose tissue and connective tissue.
  • Lungs: Lymphangioleiomyomatosis (LAM) and cysts.
  • Eyes: Hamartomas of the retina and astrocytomas usually appear as symptoms of tuberous sclerosis. Calcification is expected but visual impairment is not common.
  • Extremities: Cysts that usually form in the feet and hands, pelvic region or spine.
  • Bones: Potential skeletal abnormalities include primarily cystic lesions.

It has been observed that in more than half of the patients affected by tuberous sclerosis, pulmonary lymphangioleiomyomatosis and renal angiomyolipomas exist simultaneously [6].

Epilepsy
  • PURPOSE: This study is designed to estimate the prevalence of epilepsy associated with TSC in Sweden and to describe treatment, morbidity, and mortality of TSC patients with epilepsy.[ncbi.nlm.nih.gov]
  • Calcification can be used to evaluate pharmacoresistant epilepsy in patients with TSC. Copyright 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.[ncbi.nlm.nih.gov]
  • PURPOSE: Epilepsy surgery has been shown to be effective in treating focal epilepsy related to tuberous sclerosis complex (TSC). We analyzed the advantage of early surgical management in terms of seizure frequency and development.[ncbi.nlm.nih.gov]
  • Basic epilepsy data were available for 1965 individuals in the database.[ncbi.nlm.nih.gov]
  • Afterwards, we statistically determined variables associated with ID, ASD and intractable epilepsy.[ncbi.nlm.nih.gov]
Developmental Delay
  • In the following months the patient developed clinically a typical neurological phenotype of LND and TSC with seizures, severe dystonia and developmental delay. CONCLUSION: Acute renal failure is a rare complication of HPRT related diseases.[ncbi.nlm.nih.gov]
  • A logistic model looking at the individual impact of infantile spasms, seizure frequency, and age of seizure onset as predictors of developmental delay revealed that age of seizure onset was the most important factor in determining developmental outcome[ncbi.nlm.nih.gov]
  • Infantile spasms, generalized-tonic clonic seizures, poor seizure control, cardiac rhabdomyomas, SEGA and developmental delay were not associated with quantitative tuber characteristics.[ncbi.nlm.nih.gov]
  • If your child shows signs of developmental delay, behavioral problems, or mental impairment, early intervention can significantly improve their ability to function.[healthline.com]
  • The patient had no history of seizures or developmental delay, and he had no family history of similar cutaneous findings. Tuberous sclerosis complex is an autosomal dominant condition that affects cellular differentiation and proliferation.[nejm.org]
Weight Loss
Dyspnea
  • The patient was hospitalized 3 months earlier for dyspnea at the Department of Cardiology, where she was diagnosed with heart failure (left ventricle injection fraction: 25-30%), pulmonary hypertension, chronic kidney disease (serum creatinine: 1.58 mg[ncbi.nlm.nih.gov]
  • Lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH) and pulmonary cysts develop during adulthood and manifest with dyspnea, pneumothorax, or chylothorax.[orpha.net]
  • This may be progressive and result in dyspnea, cor pulmonale, recurrent pneumothorax, and respiratory failure. Gastrointestinal tumors may be associated. Microhamartomatous polyps are present in the rectum in 75% of cases.[emedicine.medscape.com]
  • Solitary lesions may remain clinically silent or rupture, with resultant pneumothorax producing acute dyspnea and hemoptysis.[emedicine.medscape.com]
Vomiting
  • Other ophthalmic signs and symptoms are relatively rare in this disease.We describe the case of a young woman with tuberous sclerosis who presented with horizontal binocular diplopia and decreased visual acuity without complaints of nausea, vomiting or[ncbi.nlm.nih.gov]
  • We present the case of a 35-year-old man with TSC who was admitted to our hospital for a sudden attack of serious headache, vomiting, and left hemiplegia.[ncbi.nlm.nih.gov]
  • […] reported with Votubia LE/HE vs placebo included stomatitis (54.7%/63.8% vs 9.2%), diarrhea (17.1%/21.5% vs 5.0%), nasopharyngitis (13.7%/16.2% vs 16.0%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), pyrexia (fever) (19.7%/13.8% vs 5.0%), vomiting[globenewswire.com]
  • They can present with headache, vomiting, deterioration in seizure control and focal neurological signs. Subependymal nodules (SENs) can also occur. They are small lesions found in the lining of the ventricles.[patient.info]
Nausea
  • Other ophthalmic signs and symptoms are relatively rare in this disease.We describe the case of a young woman with tuberous sclerosis who presented with horizontal binocular diplopia and decreased visual acuity without complaints of nausea, vomiting or[ncbi.nlm.nih.gov]
  • Various signs and symptoms include an unexpectedly large head size, nausea, headaches and behavior changes. Heart complications. Growths in the heart, usually in infants, can block blood flow or cause problems with heart rhythm (dysrhythmia).[mayoclinic.org]
  • Pressure from buildup (hydrocephalus) can cause headaches, nausea and behavioral changes. Young patients can suffer from tumors in the heart which may result in heart failure or conduction abnormalities.[my.clevelandclinic.org]
  • This blockage can lead to behavioral changes, nausea, headaches or a number of other symptoms. In the heart, the tumors are usually at their largest at birth and then decrease in size as the individual gets older.[tsalliance.org]
Abdominal Mass
  • Renal angiomyolipomas (AML) develop during childhood with a higher risk of growth during adolescence and adulthood and manifest by pain, hematuria/retroperitoneal hemorrhage, abdominal masses, hypertension and renal failure.[orpha.net]
  • Image in a 15-year-old boy with a right-sided abdominal mass, which is a renal cell carcinoma.[emedicine.com]
Abdominal Pain
  • This can present as haematuria, abdominal pain and hypovolaemia. Obstruction can occur as they enlarge.[patient.info]
  • Hematuria, back or abdominal pain, or internal hemorrhage may be the initial signs of kidney problems. Treatment The renal lesions that appear in many individuals with TSC may remain stable and require no specific treatment.[en.wikibooks.org]
Gingival Fibroma
  • Isolated gingival fibromas can occur in persons who do not have TSC. However, gingival fibroma(s) in association with large numbers ( 10) of dental pits is highly suggestive of TSC and should prompt further diagnostic evaluation.[emedicine.medscape.com]
  • fibromas, and hypopigmented macules. synonyms Tuberous Sclerosis, Tuberous Sclerosis, Bourneville-Pringle's Disease[dermis.net]
  • fibromas and dental pitting Axial cut section from the same case shows bilateral subependymal giant cell astrocytomas Axial graphic of typical brain involvement in tuberous sclerosis complex shows a giant cell astrocytoma in the left foramen of Monro[slideshare.net]
  • Subungual and periungual fibromas are also common after puberty; gingival fibromas may occur as well.[aao.org]
  • fibromas Nonrenal hamartoma Retinal achromic patch Confetti skin lesions Multiple renal cysts Skin lesions Skin lesions [14] are found in 70-80% of cases of tuberous sclerosis.[emedicine.medscape.com]
Hypertension
  • , hypertensive retinopathy, and sleep-apnea syndrome.[ncbi.nlm.nih.gov]
  • Author information 1 Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.[ncbi.nlm.nih.gov]
  • Polycystic kidney disease occurs in 2-3% of persons with TSC, and usually presents early in life with hypertension, hematuria, or renal failure.[emedicine.medscape.com]
  • Renal angiomyolipomas (AML) develop during childhood with a higher risk of growth during adolescence and adulthood and manifest by pain, hematuria/retroperitoneal hemorrhage, abdominal masses, hypertension and renal failure.[orpha.net]
Heart Failure
  • […] dl), and resistant hypertension and discharged with optimal heart failure treatment.[ncbi.nlm.nih.gov]
  • It can lead to intellectual handicap, epilepsy, autism, and renal or heart failure.[ncbi.nlm.nih.gov]
  • However, despite being clinically silent, these lesions can provoke arrhythmias and heart failure (Pediatrics 118:1146-1151, 2006; Eur J Pediatr 153:155-7, 1994).[ncbi.nlm.nih.gov]
  • Failure Cardiac rhabdomyomas can lead to hemodynamic compromise and congestive heart failure, and while this occurrence is rare, it remains one of the most frequent causes of death among TSC children 49 Heart failure occurs in 2% to 5% of infants and[doi.org]
  • Young patients can suffer from tumors in the heart which may result in heart failure or conduction abnormalities. These are called cardiac rhabdomyomas tumors and generally decrease in size with age.[my.clevelandclinic.org]
Retinal Lesion
  • The fingernails and toenails should also be examined for ungual fibromas, the teeth and gums for dental pits and gum fibromas, and the eyes for retinal lesions.[aocd.org]
  • lesions are glial nodules; other skin lesions are hypopigmented macules, shagreen patches, and periungual fibromas; autosomal dominant inheritance with variable expression, caused by mutation in either the tuberous sclerosis gene ( TSC1 ) on chromosome[medical-dictionary.thefreedictionary.com]
  • Investigations Investigations will depend on presenting features, but include: [ 1 ] Fundoscopy, which should be performed to look for retinal lesions. Examination of the skin with Wood's ultraviolet (UV) light (shows hypopigmented patches).[patient.info]
  • Treatment [ edit ] For the most part, treatment of the retinal lesions and repeated ophthalmologic examinations are unnecessary. Normal eye care should be maintained.[en.wikibooks.org]
Facial Angiofibroma
  • Twenty-four children completed 36 weeks of treatment with topical sirolimus; facial angiofibromas were clinically undetectable in four (17%). The mean decrease in the Facial Angiofibroma Severity Index (FASI) score at 36 weeks was 47.6 30.4%.[ncbi.nlm.nih.gov]
  • The introduction of topical rapamycin marked a turning point for treatment of facial angiofibromas; however, the lack of a standardized formulation, limited insurance coverage, and significant financial cost restrict universal access for patients and[ncbi.nlm.nih.gov]
  • The clinical features manifest as a combination of seizures, mental retardation, facial angiofibroma, renal angiomyolipoma, and cardiac rhabdomyoma. Most cases of TSC are caused by mutations of the TSC1 or TSC2 genes.[ncbi.nlm.nih.gov]
  • Systemic examination revealed facial angiofibroma, ashleaf spot, and dental pits with multiple cortical tubers on CT brain. Intravitreal injection of bevacizumab led to visual and tomographic improvement.[ncbi.nlm.nih.gov]
  • It usually presents with a triad of epilepsy, mental deficiency and facial angiofibromas that are often distributed around the nose, cheek and chin, and are frequently shaped like butterfly wings.[ncbi.nlm.nih.gov]
Shagreen Patch
  • Overall, 120 lesions from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39 lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen patches; and 14 lesions (12%), large shagreen patches.[ncbi.nlm.nih.gov]
  • Only 1 of 5 patients treated for shagreen patches showed improvement at 12 months. Treatment was well tolerated with no serious adverse events. LIMITATIONS: The small number of patients was a limitation.[ncbi.nlm.nih.gov]
  • We present a case of young man with diagnosis of tuberous sclerosis presenting multiple shagreen patches around the trunk, in the neck and genital region; large plaques with uneven surfaces on the right side of the lower back; and multiple papular lesions[ncbi.nlm.nih.gov]
  • Skin involvement includes: hypomelanotic macules (ash leaf) present within the first years of life; angiofibromas that appear at age 3-4 years as erythematous and papulonodular lesions; ungual fibromas; cephalic and lumbar (shagreen patch) fibrous plaques[orpha.net]
Hypopigmented Macule
  • Hypopigmented macules are the earliest sign.[ncbi.nlm.nih.gov]
  • The mother and other family members with the mutation were asymptomatic except for the presence of hypopigmented macules.[ncbi.nlm.nih.gov]
  • Clinical examination showed distinctive dermatological signs like hypopigmented macules, shagreen plaques, miliary fibromas, fibrous plaques and multiple angiofibromas. Oral manifestation included localised gingival enlargement.[ncbi.nlm.nih.gov]
  • Physical examination showed 4 hypopigmented macules with diameters exceeding 5 mm. Initial magnetic resonance imaging of the brain revealed diffuse edema in the bilateral cerebral cortex, cortical tubers, and subependymal nodules.[ncbi.nlm.nih.gov]
  • macules. synonyms Tuberous Sclerosis, Tuberous Sclerosis, Bourneville-Pringle's Disease[dermis.net]
Dermatologic Disorder
  • A variety of dermatological disorders have been correlated to TSC. Some of these include hypomelanotic macules, confetti skin lesions, facial angiofibromas, ungual fibromas, Shagreen's patches, and forehead plaque.[biology.kenyon.edu]
Acneiform Eruption
  • Polcari, Morphology-Based Diagnosis of Acneiform Eruptions, Pediatric Annals, 44, 8, (e188), (2015). E. D. Belousova, M. Yu. Dorofeeva, A. M. Pivovarova and O. V.[doi.org]
Impulsivity
  • In adults with TSC, poorer communication and socialisation skills, gastric health problems and impulsivity were associated with self-injury; compulsive behaviour and impulsivity were associated with aggression.[ncbi.nlm.nih.gov]
  • More nuanced studies of overactivity and impulsivity are warranted to identify priorities for intervention for these problematic behaviors in TSC, particularly given robust associations between impulsivity and self‐injury and aggression in TSC (Eden et[doi.org]
  • Hyperactive tendencies – typical behaviours associated with hyperactivity include impulsivity and overactivity.[betterhealth.vic.gov.au]
  • TAND can be investigated and considered at six levels: behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial.Behavioural problems most commonly seen include overactivity, impulsivity and sleeping difficulties.[en.wikipedia.org]
  • An electrocardiogram records the heart’s electrical impulses and may reveal abnormal electrical patterns. Standard Therapies Treatment Treatment may require the coordinated efforts of a team of specialists.[rarediseases.org]
Anxiety Disorder
  • She proceeded to perform systematic evaluations and confirmed a high rate of anxiety disorder meeting ICD‐10 criteria.[doi.org]
  • Anxiety disorders. Sleep disorders. Epilepsy-related psychotic disorders. Cardiac involvement Cardiac rhabdomyomas are seen in the majority of young children with tuberous sclerosis.[patient.info]
  • Less common are depressed mood, self-injury and obsessional behaviours.People with TSC are frequently also diagnosed psychiatric disorders: autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), anxiety disorder and depressive[en.wikipedia.org]
Abnormal Behavior
  • After the second year of life, abnormal behaviors including hyperactivity, rituals, repetitive behaviors, and temper tantrums can appear (Jeste et al., 2008 ).[doi.org]
Kidney Failure
  • Growths in the kidney can cause high blood pressure or bleeding or lead to kidney failure. Rarely, kidney growths can become cancerous. Lung failure.[mayoclinic.org]
  • Large tumors can get in the way of normal kidney function and lead to kidney failure. If tumors in the eye grow too large, they can block the retina, causing vision loss or blindness.[healthline.com]
  • Later in life, TSC can make its mark with kidney tumors and kidney failure. Patients with a mild form of the disease may remain undiagnosed– and family members unaware of their genetic risks – until later in life when TSC may attack vital organs.[my.clevelandclinic.org]
  • In the past, kidney failure was almost inevitable. Today, doctors can use drug therapy to shrink angiomyolipomas or can destroy individual tumors by embolization before they get too large and compromise healthy kidney tissue.[tsalliance.org]
Hematuria
  • The 22-year-old man was admitted due to bilateral flank pain, gross hematuria, and abdominal fullness. He had history of epilepsy, mental retardation, and delayed development during childhood. He had angiofibroma on his face since 10 years ago.[ncbi.nlm.nih.gov]
  • Renal angiomyolipomas (AML) develop during childhood with a higher risk of growth during adolescence and adulthood and manifest by pain, hematuria/retroperitoneal hemorrhage, abdominal masses, hypertension and renal failure.[orpha.net]
  • Polycystic kidney disease occurs in 2-3% of persons with TSC, and usually presents early in life with hypertension, hematuria, or renal failure.[emedicine.medscape.com]
  • Usually, hamartomas are asymptomatic; however, they can cause flank pain, hematuria, or an abdominal mass, which may be palpable. Hamartomas usually are multiple and bilateral.[emedicine.com]
Flank Pain
  • The 22-year-old man was admitted due to bilateral flank pain, gross hematuria, and abdominal fullness. He had history of epilepsy, mental retardation, and delayed development during childhood. He had angiofibroma on his face since 10 years ago.[ncbi.nlm.nih.gov]
  • One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients.[ncbi.nlm.nih.gov]
  • They often produce nonspecific complaints such as flank pain. Of rather more concern is potentially life-threatening retroperitoneal hemorrhage from rupture of dysplastic, aneurysmal blood vessels.[emedicine.medscape.com]
  • Usually, hamartomas are asymptomatic; however, they can cause flank pain, hematuria, or an abdominal mass, which may be palpable. Hamartomas usually are multiple and bilateral.[emedicine.com]
  • In some instances, they may cause flank pain or kidney (renal) dysfunction. Angiomyolipomas are prone to rupturing and bleeding (hemorrhaging), which can potentially become life-threatening (approximately 20% of the time).[rarediseases.org]
Amenorrhea
  • The most common events were amenorrhea (24.1%) and irregular menstruation (17.0%). Seven patients (6.3%) experienced grade 3/4 amenorrhea.[ncbi.nlm.nih.gov]
Seizure
  • Patients with a history of seizures not only performed worse, but developmental progress lagged behind the group without seizures.[ncbi.nlm.nih.gov]
  • Our patients were started on vigabatrin after the onset of focal seizures with the aim of preventing seizure recurrence, halting the possible progression to infantile spasms or focal seizures, and preventing neurodevelopmental decline.[ncbi.nlm.nih.gov]
  • Seizure control was established in the first year of rapamycin therapy in all cases. An increased frequency of seizures was observed in three cases after the second year of treatment.[ncbi.nlm.nih.gov]
  • KEYWORDS: clinically silent seizure; ictal electroencephalogram; neonatal seizure; polygraph; tuberous sclerosis[ncbi.nlm.nih.gov]
  • The percentages of seizure-free cases were 74.5% at 1FU, 58.8% at 5FU, and 47.8% at 10FU, and the predictive factor for long-term postoperative seizure freedom was the history of preoperative seizures and preoperative full-scale IQ.[ncbi.nlm.nih.gov]
Headache
  • Other ophthalmic signs and symptoms are relatively rare in this disease.We describe the case of a young woman with tuberous sclerosis who presented with horizontal binocular diplopia and decreased visual acuity without complaints of nausea, vomiting or headache[ncbi.nlm.nih.gov]
  • We present the case of a 35-year-old man with TSC who was admitted to our hospital for a sudden attack of serious headache, vomiting, and left hemiplegia.[ncbi.nlm.nih.gov]
  • We present a case of a 25-year-old female with no medical history who presented to the emergency room for headaches.[ncbi.nlm.nih.gov]
  • Various signs and symptoms include an unexpectedly large head size, nausea, headaches and behavior changes. Heart complications. Growths in the heart, usually in infants, can block blood flow or cause problems with heart rhythm (dysrhythmia).[mayoclinic.org]
Tonic-Clonic Seizure
  • Infantile spasms, generalized-tonic clonic seizures, poor seizure control, cardiac rhabdomyomas, SEGA and developmental delay were not associated with quantitative tuber characteristics.[ncbi.nlm.nih.gov]
  • If they spread to involve a large enough area of the brain, partial seizures can turn into a generalized tonic-clonic seizure. So it is possible for a patient to have both types of seizures.[my.clevelandclinic.org]
  • Focal seizures can present with forced eye or head deviation, rhythmic jerking of an extremity, change in response, or evolve to a generalized convulsive ( tonic-clonic ) seizure.[epilepsy.com]
  • Complex partial and tonic-clonic seizures can also occur. Subependymal giant cell astrocytoma (SEGA) may develop in a minority of patients. These can grow and can lead to hydrocephalus (due to their location at the foramen of Munro).[patient.info]
Confusion
  • It may be confused with autism. Bourneville, Désiré-Magloire, French physician, 1840-1909. Bourneville disease - phacomatosis characterized by the formation of multisystem hamartomas.[medical-dictionary.thefreedictionary.com]
  • Can be confused with acne. Fibrous plaques (M): yellow-brown patches seen on the scalp/forehead Ungual/periungual fibromas: flesh-colored/pink bumps seen in the nail plate or on the side of the nail. Typically appear around adolescence.[epilepsy.com]
  • Sometimes multiple renal cysts can be confused with true polycystic kidney disease. The presence of significant symptoms such as hypertension or failure to thrive, as well as the absence of associated AMLs, strongly suggest the latter diagnosis.[emedicine.medscape.com]
  • For example, arrhythmia may cause fainting that is confused with drop seizures, and symptoms of arrhythmia such as palpitations may not be reported in an individual with developmental delay.[en.wikipedia.org]
  • Second, the theme of “coping with the disease” described stages (akin to the stages of grief) from alarm/confusion, to panic/refusal, anxiety/isolation, to final acceptance/aggregation.[doi.org]
Sleep Disturbance
  • Secondary objectives Comparison of absolute change from baseline in frequency of epileptiform events as recorded on seizure diaries between patients taking RAD001 vs. placebo Comparison of sleep disturbances between patients taking RAD001 vs. placebo,[clinicaltrials.gov]
  • Individuals can potentially develop a range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), sleep disturbances or disorders, learning and cognitive impairments, or behavioral issues including[rarediseases.org]

Workup

Patients with tuberous sclerosis present with fluctuating clinical pictures, due to the multiplicity of the locations where the tumors may form.

In order to diagnose tuberous sclerosis, either of the two diagnostic criteria must be met:

  • 2 major features or 1 major feature plus 2 minor: The patient definitely suffers from tuberous sclerosis
  • 1 major feature or 2 or more minor features: The patient possibly suffers from tuberous sclerosis.

Under the category of major features fall the following abnormal findings:

Minor features:

Depending on the pathological findings, various other laboratory or imaging tests can be performed. Renal hamartomas can be monitored with urinalysis and an electrolyte test. Cortical tubers, SENs and SEGAs can be illustrated and followed-up with the use of a magnetic resonance imaging scan (MRI) [7] or a computerized tomography scan (CT).

Renal abnormalities are best pictured with the use of ultrasonography. CT and MRI scans can further be used to monitor patients with renal dysfunction due to lesions every six to twelve months; CT scans should be conducted as less frequently as possible, due to the radiation the patient is exposed to. Cardiac rhabdomyomas usually subside as the disease progresses and can be revealed and monitored with the use of echocardiography; an electrocardiogram is also useful in order to perform an adequate follow up. Pulmonary lesions are visible on an x-ray or a CT scan.

With reference to additional affected systems, fundoscopy is the examination of choice in order to detect and closely monitor patients with tuberous sclerosis and ocular irregularities. Up to 80% of retinal hamartomas are visible via fundoscopy.

Multiple Renal Cysts
  • On magnetic resonance imaging, 18 children exhibited subependymal nodules, and 16 ones showed cortical nodules. 5 cases of non-renal hamartomas, 5 cases of multiple renal cysts, and 5 cases of cardiac rhabdomyomas were observed.[ncbi.nlm.nih.gov]
  • renal cysts Skin lesions Skin lesions [14] are found in 70-80% of cases of tuberous sclerosis.[emedicine.medscape.com]
  • renal cysts; retinal achromatic patches) features.[orpha.net]
  • Multiple renal cysts. Skin tags. Positive family history in a first-degree relative. Investigations Investigations will depend on presenting features, but include: [ 1 ] Fundoscopy, which should be performed to look for retinal lesions.[patient.info]
Pericardial Effusion
  • Fetal cardiac tumors may present in utero as a mass on ultrasonography, irregular heart rhythm, hydrops fetalis, or pericardial effusion.[doi.org]
Cortical Tubers
  • KEYWORDS: Cortical tuber; Epilepsy; Focal cortical dysplasia; Hippocampal sclerosis; Tuberous sclerosis[ncbi.nlm.nih.gov]
  • Tuberous sclerosis complex (TSC) is a disorder that frequently leads to the development of refractory seizures by multiple cortical tubers. The multiple cortical tubers cause multiple or wide epileptic networks in these cases.[ncbi.nlm.nih.gov]
  • Early appearance of cortical tubers on cerebral ultrasound in newborn infants is very rare. Mostly TSC is diagnosed on MRI and not by cerebral ultrasound.[ncbi.nlm.nih.gov]
  • Systemic examination revealed facial angiofibroma, ashleaf spot, and dental pits with multiple cortical tubers on CT brain. Intravitreal injection of bevacizumab led to visual and tomographic improvement.[ncbi.nlm.nih.gov]
  • It is also associated with cortical tuber and hamartomas formation throughout the body, especially the heart, kidneys, and eyes.[icd9data.com]

Treatment

The most challenging and potentially life-threatening symptom related to tuberous sclerosis is epilepsy. Epilepsy should be treated in the same way a non-TSC epilepsy is managed: a single medication is administered in the minimum dosage, which is progressively increased until a therapeutic effect is attained. In cases of drug inefficacy, the antiepileptic drug is changed. A double-drug regime is followed only if the monotherapy does not produce the necessary control. In cases of patients with brain lesions, the administration of anticonvulsive medications should be initiated before seizures start to occur [8] [9] [10].

Should a patient present with lymphangioleiomyomatosis, hormonotherapy may be chosen to treat the symptom. Progesterone in combination with an oophorectomy is the treatment of choice. Hypertension occurring as a result of renal dysfunction can be managed with antihypertensive medications and inotropic agents can help to improve the heart's contractility, if the patient suffers from cardiac disease.

The two drugs exclusively used for the management of tuberous sclerosis are everolimus and sirolimus. Given that the products of the TSC1 and TSC2 genes, tuberin and hamartin, actually inhibit the mammalian target of rapamycin complex 1 and tuberous sclerosis patients posses mutated genes, these drugs aim at the compensation of this inadequacy. They act in replacement of the dysfunctional proteins and hinder cellular growth, in order to prevent tumors from forming.

Prognosis

Tuberous sclerosis leads to the formation of benign hamartomas in various locations of the body. Even though the tumors may be quite extensively dispersed, the absence of malignancy renders their prognosis better than it was originally believed. Naturally, the location of the tumor stipulates the rates of morbidity and mortality.

Patients with tuberous sclerosis may have a relatively low quality of living, given that even benign hamartomas can disrupt the functionality of the organs. Death or serious complications, however, are a result of tumors located in the brain and is usually brought on by epileptic seizures or falls and traumatizations that occur as a result of epileptic phenomena. Brain tumors can also lead to an elevated intracranial pressure (hydrocephalus) and antiepileptica can also lead to fatal complications when administered for a long period of time or in an excessive manner. Additionally, hamartomas located on the heart can cause life-threatening arrhythmia, even though they are usually self-restricting.

Another factor that considerably contributes to the elevated morbidity and/or mortality that accompanies tuberous sclerosis is the difficulty to diagnose and effectively manage cases of the disease. A significant number of patients remain undiagnosed or undergo unnecessary and/or possibly risky surgical operations in order to excise a tumor that could also be monitored.

Etiology

Tuberous sclerosis is a genetic disease; it is inherited via the autosomal dominant inheritance pathway.

The genetic abnormality that leads to such a clinical picture has been identified as a mutation in the TSC1 or TSC2 gene: they encode for tuberin and hamartin, proteins that inhibit the mammalian target of rapamycin complex 1 (mTORC1). The latter controls the process of cellular growth and metabolic process and without the inhibitory effect of hamartin and tuberin, hyperplasias and benign tumors can form in virtually every part of the body. It has been calculated that the most common mutations affect the TSC2 gene.

Epidemiology

Tuberous sclerosis is not commonly encountered in the daily clinical practice, as it affects 40,000 people in the USA. The prevalence has been exhibiting a steady increase during the past years, which has been attributed to the establishment of different criteria and the improvement of diagnostic efficacy.

At an international level, tuberous sclerosis seems to affect approximately 2,000,000 people in the whole world. The type of gene affected by the mutation seems to be dependent upon ethnicity, with some populations presenting with a higher ratio of TSC1/TSC2 mutations when compared to others.

Sex distribution
Age distribution

Pathophysiology

The pathophysiological background of tuberous sclerosis has been mapped since approximately 1993, mutations in the genes TSC1 and TSC2 are responsible for the occurrence of tuberous sclerosis. They are located on chromosomes 9 and 16 respectively and, although their role has yet to be fully illustrated, they are known to play an inhibitory role in the process of cellular growth and differentiation through an interaction with beta-catenin.

Both genes exert an inhibitory effect on the process of cellular growth; they are therefore responsible for controlling the expansion of tumors and preventing tumorigenesis throughout the entire organism. Mutations in those two genes result in an unregulated proliferation of cells and hamartomas. The exact pathway seems to require a second-hit mutation and a LOH (loss of heterozygosity) for a hamartoma to occur, with the exception of brain tumors comprising giant cells.

TSC1 and TSC2 constitute the standard genes that are subject to mutations and induce the condition known as tuberous sclerosis. The types of mutations responsible for the disease vary, with more than 1,800 distinct mutations recognized.

Prevention

Tuberous sclerosis is a genetic condition which is inherited in an autosomal dominant way and can therefore not be prevented. However, the possibility for a diagnosis before a child is born exists and genetic testing should be performed if a parent is diagnosed with the disease.

Summary

Tuberous sclerosis complex (TSC) or, simply, tuberous sclerosis, is a genetic disease which induces multiple tumors to form in diverse regions of the body. These tumors have no malignant characteristics but nevertheless interfere with each organ's function. The organs that are primarily affected are the lungs, brain, heart and kidneys.

Depending on the location of the tumors, the functionality of the organs may be severely compromised and life-threatening sequelae may be caused, such as hydrocephalus and epilepsy. Disfigurement due to skin tumors may lower the quality of life for a patient and the multitude of the symptoms that can arise definitely renders the individuals affected by the disease considerably disabled. Various degrees of mental disability accompany the clinical picture almost in 80% of the cases and developmental disorders may also be present [1] [2] [3].

Patient Information

Tuberous sclerosis is a rare genetic condition. It leads to the formation of benign tumors in various locations of the body, which interfere with the normal function of the organs they are found on.

The condition is a result of a mutation on two specific genes, TSC1 and TSC2. These genes produce two proteins, which prevent the formation of tumors because they prevent cells from growing excessively. The mutations produce faulty proteins, which cannot stop the rapid reproduction of cells and, therefore, tumors are allowed to develop.

Since patients with tuberous sclerosis can have lesion in many organs, the symptoms they experience are multiple and depend on the organ that is affected. The most severe and possibly life-threatening symptom is epilepsy, caused by brain tumors.

Tuberous sclerosis is diagnosed based on a set of criteria, depending on the symptoms. Treatment follows a symptomatic plan, which means that each patient is treated accordingly, depending on the clinical picture they present with. Two drugs, everolimus and sirolimus, are currently studied for their potential contribution to the management of tuberous sclerosis patients in general.

References

Article

  1. De Waele L, Lagae L, Mekahli D. Tuberous sclerosis complex: the past and the future. Pediatr Nephrol. 2014 Dec 23.
  2. DiMario FJ Jr, Sahin M, Ebrahimi-Fakhari D. Tuberous Sclerosis Complex. Pediatr Clin North Am. 2015;62(3):633-648.
  3. Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol. 2015;14(7):733-745.
  4. Samueli S, Abraham K, Dressler A, Groeppel G, Jonak C, Muehlebner A, Prayer D, Reitner A, Feucht M; Pädiatrisches TSC-Zentrum Wien. Tuberous Sclerosis Complex: new criteria for diagnostic work-up and management. Wien Klin Wochenschr. 2015 Apr 10
  5. Jacks SK, Witman PM. Tuberous Sclerosis Complex: An Update for Dermatologists.
    Pediatr Dermatol. 2015 Mar 17.
  6. von Ranke FM, Zanetti G, E Silva JL, Neto CA, Godoy MC, Souza CA, Mançano AD, Souza AS Jr, Escuissato DL, Hochhegger B, Marchiori E. Tuberous Sclerosis Complex: State-of-the-Art Review with a Focus on Pulmonary Involvement. Lung. 2015 Jun 24.
  7. Manoukian SB, Kowal DJ. Comprehensive imaging manifestations of tuberous sclerosis. AJR Am J Roentgenol. 2015;204(5):933-43
  8. Tran LH, Zupanc ML. Long-Term Everolimus Treatment in Individuals With Tuberous Sclerosis Complex: A Review of the Current Literature. Pediatr Neurol. 2015;53(1):23-30.
  9. Davis PE, Peters JM, Krueger DA, Sahin M. Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism. Neurotherapeutics. 2015;12(3):572-83.
  10. Leclezio L, de Vries PJ. Advances in the treatment of tuberous sclerosis complex. Curr Opin Psychiatry. 2015;28(2):113-20.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 21:25