Version May 2024
INTRODUCTION — Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder that is characterized by pleomorphic features involving many organ systems, including multiple benign hamartomas of the brain, eyes, heart, lung, liver, kidney, and skin [1-3]. The expression of the disease varies substantially. The diagnosis of TSC can be made clinically or through genetic testing.
The clinical features of TSC will be reviewed here. Other aspects of TSC are discussed elsewhere:
●(See "Tuberous sclerosis complex: Genetics and pathogenesis".)
●(See "Tuberous sclerosis complex: Evaluation and diagnosis".)
●(See "Tuberous sclerosis complex: Management and prognosis".)
●(See "Renal manifestations of tuberous sclerosis complex".)
●(See "Tuberous sclerosis complex associated lymphangioleiomyomatosis in adults".)
EPIDEMIOLOGY — Most reports suggest the incidence of TSC is 1 in 6000 to 1 in 10,000 live births [3-9]. The incidence does not differ by sex or race/ethnicity [10].
VARIABLE PHENOTYPE — TSC is characterized by the development of a variety of benign tumors in multiple organs, including the brain, heart, skin, eyes, kidney, lung, and liver [3,11]. Nearly all patients with TSC have one or more of the skin lesions that are characteristic of the disorder. Many patients with TSC have epilepsy, and one-half or more have cognitive deficits and learning disabilities. However, there is a wide variety of phenotypes among and within families regarding the number and severity of TSC manifestations [12,13]. The classic Vogt diagnostic triad, consisting of seizures, intellectual disability, and facial angiofibromas [14], occurs in less than one-third of patients with TSC [2].
Possible manifestations of TSC reported in occasional patients include vascular anomalies, limb overgrowth (hemihypertrophy), and segmental lymphedema [15-18].
In addition, there is an increased risk of malignancy in TSC. (See "Tuberous sclerosis complex: Management and prognosis", section on 'Risk of invasive malignancy'.)
PRESENTATION — TSC is a progressive disorder, but the individual features have different natural histories. In addition, because the expression of TSC varies significantly among patients and within families, it is difficult to predict the extent to which a child with newly diagnosed disease will be affected.
Infancy — Common presentations of TSC in infancy include seizures, hypomelanotic macules, and detection of cardiac rhabdomyoma [19-21].
In a longitudinal study of 125 patients with TSC, the median age at presentation was seven months [19]. Seizures were the most common presentation of TSC in infancy or early childhood, accounting for 62 percent of cases. An abnormality on prenatal ultrasound, mainly cardiac rhabdomyoma, was the second most common presentation, accounting for 14 percent of cases. Presentation before the onset of seizures was not uncommon, occurring in 24 percent. Similarly, a retrospective review that included 101 infants with TSC diagnosed within the first week to 12 months of life found that most presented with new-onset seizures, infantile spasms, or hypomelanotic macules [20].
Childhood — TSC often presents with seizures in childhood (see 'Seizures and epilepsy' below), and many of the dermatologic features of TSC become apparent during childhood, when hypomelanotic macules and forehead plaque are seen, or during adolescence, when angiofibromas of the face become visible. (See 'Dermatologic manifestations' below.)
Complications caused by the growth of subependymal giant cell astrocytomas (also known as subependymal giant cell tumors) are also most likely to occur during childhood, with these lesions stabilizing in the teens to twenties. (See 'Brain lesions' below.)
In a retrospective review, there were 74 children with TSC diagnosed from age 1 to 10 years, and most presented with new-onset seizures or a history of seizures [20]. In addition, a family history of TSC and dermatologic features were common presenting features. Among 16 patients diagnosed from ages 11 to 20 years, the most common presenting features were new-onset seizures and angiofibromas.
Adulthood — Features of TSC that are likely to first present in adulthood as significant problems include renal angiomyolipoma, periungual fibroma, and lymphangioleiomyomatosis. (See 'Dermatologic manifestations' below and 'Renal manifestations' below and 'Pulmonary manifestations' below.)
The diagnosis of TSC is sometimes made in adults after the diagnosis is made in an affected child, particularly if the parent is mosaic for a TSC complex subunit 1 (TSC1)/TSC complex subunit 2 (TSC2) pathogenic variant and is mildly affected. In a retrospective review that included 23 patients diagnosed with TSC as adults, most presented because of a new diagnosis in a family member or a known family history of TSC [20]. (See "Tuberous sclerosis complex: Evaluation and diagnosis", section on 'Parental evaluation'.)
BRAIN LESIONS
Glioneuronal hamartomas and subependymal nodules — Both cortical glioneuronal hamartomas and subependymal nodules (SENs) are regarded as hamartomas (a benign mass of disorganized tissue native to a particular anatomic location).
●Cortical glioneuronal hamartomas (image 1) are composed histologically of enlarged atypical and disorganized neuronal and glial elements with astrocytosis. In keeping with their hamartomatous nature, "glioneuronal hamartoma" is preferred in place of the outdated term "tuber" when describing a finding in patients.
●SENs are also composed of atypical enlarged glial and neuronal cells. These nodules (image 2) are indistinguishable histologically from subependymal giant cell astrocytomas (SEGAs), also known as subependymal giant cell tumors (SGCTs) (image 3), except for their small size. (See 'Subependymal giant cell astrocytomas' below.)
Cortical glioneuronal hamartomas and SENs are present on brain magnetic resonance imaging (MRI) in approximately 90 percent of children with TSC [19,22,23]. The detection rate of these lesions is moderately lower on computed tomography (CT). Cortical glioneuronal hamartomas may be calcified on CT scan in approximately one-half of patients, and SENs are usually calcified on CT except in the early years of life [22,24,25]. To minimize radiation exposure, the use of CT monitoring for children with TSC should be limited. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'CT safety considerations'.)
The extent of cerebral dysfunction (ie, seizure status and cognitive function) in TSC is only loosely related to the burden of glioneuronal hamartomas as demonstrated on cranial imaging. In a meta-analysis of five studies, the number of MRI-detected glioneuronal hamartomas in patients with TSC and severe cerebral dysfunction (ie, poor seizure control and/or moderate to severe intellectual disability) was six times more likely to be above the median compared with mildly affected patients [26]. Because glioneuronal hamartomas form during embryogenesis, disruption of normal cortical development and function occurs early in gestation. In a later study of 61 patients with TSC, the proportion of brain volume occupied by glioneuronal hamartomas was inversely related both to age at seizure onset and to cognitive function [27]. However, the relationship was not invariant, as some patients with a large glioneuronal hamartoma volume had normal intelligence. Cortical glioneuronal hamartomas with central low signal on fluid-attenuated inversion recovery (FLAIR) MRI may predict a higher risk of epilepsy in TSC [28]. (See 'Seizures and epilepsy' below.)
Subependymal giant cell astrocytomas — The characteristic brain tumor in TSC is the SEGA (image 3 and picture 1), which is a benign, slow-growing tumor that usually arises in the periventricular area [29-32]. SEGAs are thought to arise from the growth of SENs. Although most often called "subependymal giant cell astrocytomas," they are of mixed glioneuronal lineage; thus "subependymal giant cell tumors" is a more accurate description.
The prevalence of SEGAs in TSC ranges from 5 to 20 percent in different studies [5]. As noted, the distinction between SENs and SEGAs may be largely semantic.
Evidence from radiologic studies supports the hypothesis that SEGAs can arise from the growth of preexisting SENs, the latter occurring in 88 to 95 percent of children with TSC [33-35]. However, the apparent absence of SENs on neuroimaging does not eliminate the risk of developing a SEGA. It is not clear why some SENs grow (and therefore are termed SEGAs) while others do not. Neoplastic transformation of SENs/SEGAs is rare.
Symptomatic SEGAs occur in 6 to 9 percent of individuals with TSC [29,36,37]. The tumors usually become symptomatic between the ages of 10 and 30, although they can occur as early as 1.5 years [31,38]. Affected children typically present subacutely with signs and symptoms of obstructive hydrocephalus, such as headaches and vomiting, or with focal neurologic deficits, including vision loss [29-31,36,39]. In addition, children may present with nonspecific symptoms such as fatigue, depression, decreased appetite, and increased seizure frequency [29].
Diagnostic features associated with increased morbidity are likely to have the most clinical utility for decision-making regarding subependymal lesions (whether SENs or SEGAs); these include [29]:
●New symptoms or papilledema
●Hydrocephalus
●Growth of the lesion on serial imaging
In most cases, the presence of these criteria should define the lesion as a SEGA rather than a SEN, independent of tumor size, location, signal characteristics, or contrast enhancement [29]. Radiologic evidence of hydrocephalus may not be prominent on neuroimaging studies in patients with TSC even when increased intracranial pressure due to SEGA is present; in such cases new symptoms or papilledema may be present, perhaps due to altered periventricular compliance [29].
White matter lesions — White matter lesions are common in patients with TSC [40]. These include nodules, cysts, and areas of gliosis and hypomyelination. Linear white matter lesions may be visualized by MRI in approximately 15 percent of children with TSC [40]. These linear lesions are hyperintense on T2-weighted MRI and are either isointense or hypointense on T1 images. They typically extend from the ventricle to the cortex, with a SEN or subcortical lesion on each end; they are thought to represent demyelination, dysmyelination, or hypomyelination from a migration disorder [41].
Microscopic white matter lesions are characteristically present in patients with TSC [42]. Even normal-appearing white matter may show pathologically increased water diffusivity (ie, an increased apparent diffusion coefficient) by diffusion-weighted MRI [43].
Arachnoid cysts — In a retrospective review of brain MRIs from 220 patients with TSC, asymptomatic arachnoid cysts were noted in approximately 5 percent; this compares with an estimated prevalence in the general population of 0.5 to 1 percent [44]. Thus, arachnoid cysts may be part of the clinical spectrum of TSC.
SEIZURES AND EPILEPSY — Seizures are the most frequent presenting feature of TSC, and epilepsy is one of the most frequent and significant causes of morbidity in TSC, affecting 79 to 90 percent of patients in population-based studies [19,45]. Seizures begin in the first year of life in just over 60 percent of cases; however, patients with TS remain at risk for new-onset seizures into adult life [19,46,47]. In a natural history study that included 248 patients with TSC who had a single seizure, epilepsy subsequently developed in 246 (99 percent) [47].
Despite the frequency of seizures in TSC, epilepsy is not one of the diagnostic criteria because of the large number of disorders that are associated with seizures, including infantile spasms. (See "Tuberous sclerosis complex: Evaluation and diagnosis", section on 'Diagnosis'.)
●Seizure types – Infantile spasms are the most common type in infancy at initial diagnosis, occurring in 36 to 69 percent of patients [48]. Conversely, up to 25 percent of children with infantile spasms may have TSC [49]. (See "Infantile epileptic spasms syndrome: Clinical features and diagnosis".)
Other seizure types that occur in TSC include focal-onset seizures with and without impaired awareness, focal-onset to bilateral tonic-clonic seizures (previously termed secondarily generalized), subclinical seizures, and, less commonly, generalized onset seizures [47,50].
●EEG findings – Approximately 75 percent of patients with TSC have epileptiform abnormalities on routine electroencephalography (EEG). These include focal or multifocal discharges, hypsarhythmia, and generalized spike-wave abnormalities in 48, 19, and 8 percent, respectively [49].
●Risk factors – Risk factors for the development of epilepsy include the presence of cortical glioneuronal hamartomas (tubers) and pathogenic TSC2 variants [51].
Cortical glioneuronal hamartomas with central low signal on fluid-attenuated inversion recovery (FLAIR) MRI may predict a higher risk of epilepsy in TSC [28]. The majority of cortical glioneuronal hamartomas show homogeneous high signal on FLAIR MRI. However, some cortical glioneuronal hamartomas, sometimes called "cyst-like" though they are not true cysts, show central low signal intensity on FLAIR and T1-weighted sequences and increased signal on T2-weighted sequences. In a retrospective study of 173 patients with TSC, epilepsy was significantly more frequent in patients with at least one cortical glioneuronal hamartoma of low FLAIR and T1 signal intensity compared with those without (92 versus 76 percent, relative risk [RR] 1.22, 95% CI 1.07-1.40) [28]. Similarly, refractory epilepsy was significantly more common in patients with at least one cortical glioneuronal hamartoma of low FLAIR and T1 signal intensity (80 versus 54 percent, RR 1.47, 95% CI 1.18-1.83).
Not all cortical glioneuronal hamartomas are epileptogenic, and patients with TSC and epilepsy may have normal brain MRI studies, raising significant questions about the role of glioneuronal hamartomas in producing seizures [52]. Furthermore, epileptic foci can shift over time.
TSC-ASSOCIATED NEUROPSYCHIATRIC DISORDERS (TAND) — Most patients with TSC have one or more of the disorders that comprise TAND. These include intellectual disability, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), behavioral problems, psychiatric disorders, neuropsychologic deficits, school problems, and occupational difficulties [53,54]. These problems are often associated with brain lesions including glioneuronal hamartomas (also called tubers), periventricular giant cell astrocytomas, and abnormalities of cerebral white matter detected on neuroimaging studies [1,55]. (See 'Brain lesions' above.)
Intellectual disability — Intellectual disability is a primary feature of TSC, affecting 44 to 65 percent of patients in population-based reports [19,45]. It is associated with a history of infantile spasms [45,47,56,57], refractory seizures [47,58,59], and, to a lesser extent, number of glioneuronal hamartomas [60,61]. In a cohort of over 1600 patients from a TSC database, epilepsy onset before the age of two years was associated with a higher frequency and severity of intellectual disability [62]. Epilepsy was also associated with autism and attention deficit hyperactivity disorder. (See "Specific learning disorders in children: Clinical features", section on 'Risk factors'.)
There are conflicting data as to whether intellectual disability is less frequent with pathogenic variants involving TSC1 compared with those involving TSC2, a question that is further complicated by a potential association between TSC2 and an increased risk for epilepsy, including infantile spasms [47,59]. (See "Tuberous sclerosis complex: Genetics and pathogenesis", section on 'Genotype-phenotype correlations'.)
Like other features of TSC, the range of intelligence in affected patients is highly variable. In one study of standardized testing in 108 patients with TSC, intelligence quotient (IQ) scores had a bimodal distribution [45]. In 55 percent of patients, IQ was in the normal range, while 14 percent had mild to severe impairment, and 30 percent had profound disability (IQ <21). Even among the children with a normal range IQ, scores were 10 points lower on average than their unaffected siblings. All the children with learning disabilities had a history of seizures, usually infantile spasms, which began before one year of age.
A history of immunization for diphtheria, tetanus, and pertussis was not a risk factor for poor cognitive development in a review of 106 patients with TSC [56].
Autism spectrum disorder — ASD and autistic behaviors, including hyperactivity, inattention, and self-injurious behavior, are common in children with TSC and can be a significant source of stress for parents and caregivers [63-68]. In different case series, the prevalence of significant behavioral problems among children with TSC ranges from 40 to 90 percent. While behavioral problems can occur in the setting of either normal intelligence or cognitive dysfunction, at least one case series found that low intellectual functioning and higher seizure frequency were risk factors for behavioral disorders [66].
Whether ASD is associated with a specific location of glioneuronal hamartomas is uncertain. In one study, development of ASD was associated with the presence of temporal lobe glioneuronal hamartomas, temporal lobe epileptiform discharges, and early onset of persistent infantile spasms [69]. Another study evaluated 115 patients with TSC, including 31 with ASD, and found that glioneuronal hamartoma (tuber) in the right fusiform face area of the inferior temporal lobe was associated with an increased risk of ASD (odds ratio 3.69, 95% CI 1.53-8.93) [70]. However, others have shown that the frequency of glioneuronal hamartomas in the subcortical or cortical regions was similar in TSC patients with and without ASD [53,71].
The clinical features and diagnosis of ASD are discussed separately. (See "Autism spectrum disorder in children and adolescents: Clinical features" and "Autism spectrum disorder in children and adolescents: Evaluation and diagnosis", section on 'Diagnosis'.)
Attention deficit hyperactivity disorder — The estimated prevalence of ADHD in individuals with TSC ranges from 30 to 50 percent [72-74]. This prevalence is much higher than the prevalence of ADHD in the general population. The risk of ADHD in TSC has been associated with frontal lobe seizures or EEG abnormalities and pathogenic variants in TSC2, but causation has not been established [72,73,75]. (See "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis" and "Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis".)
Behavioral problems — One-third or more of individuals with TSC exhibit at least one behavioral problem, which includes behaviors that are not psychiatric disorders but can cause difficulties for patients and families [72,76]. The types of problems include the following [72]:
●Overactivity
●Impulsivity
●Sleep difficulties
●Anxiety
●Mood swings
●Aggressive behaviors
●Temper tantrums
●Poor eye contact
●Repetitive and ritualistic behaviors
●Speech and language delay
SYSTEMIC INVOLVEMENT
Dermatologic manifestations — In population-based studies, 81 to 95 percent of patients with TSC have one of the characteristic skin lesions [19,77]. The most common lesions are:
●Hypomelanotic macules – Also known as hypopigmented macules or ash-leaf spots, hypomelanotic macules are usually elliptic in shape and may require evaluation with a Wood's lamp (ultraviolet) to visualize (picture 2 and picture 3).
●Fibrous cephalic plaques – These are distinctive brown fibrous plaques on the forehead, which may be the first and most readily recognized feature of TSC to be appreciated on physical examination of affected neonates and infants (picture 4) [77].
●Angiofibromas – Also known as fibroadenomas, angiofibromas are benign tumors that typically involve the malar regions of the face (picture 5).
●Ungual fibromas – Also known as periungual or subungual fibromas (Koenen tumors), ungual fibromas are erythematous, polypoid, digitated growths. They may produce a longitudinal groove in the nail plate due to matrix compression (picture 6 and picture 7).
Ungual fibromas may develop during adolescence or adulthood (picture 7), and they occur more commonly on the toenails than on the fingernails [77-79]. Given the variable age of onset, it is important for the clinician to inspect the nails of both the patient and the parents when first doing an evaluation for TSC. Longitudinal nail grooves without visible fibromas are also commonly seen [78]. Less frequent acral lesions include subungual red comets (red longitudinal streaks with a larger distal head and a narrowing proximal tail), splinter hemorrhages, and longitudinal leukonychia (white streaks extending from the nail matrix to the end of the nail).
A solitary ungual fibroma as a result of trauma is not a diagnostic feature of TSC [7,80]. On the other hand, a history of trauma in a patient presenting with an ungual fibroma should not be used to discount the possibility of TSC [78].
●Shagreen patches – These are connective tissue nevi, seen most commonly over the lower back (picture 8) [81].
Hypomelanotic macules and fibrous cephalic plaques typically appear earlier than facial angiofibromas or ungual fibromas [77].
There is no significant risk of malignant transformation of skin lesions, which tend to increase in size and number through puberty and then tend to be stable over time.
Ophthalmic manifestations — Ophthalmic findings in TSC include both retinal and nonretinal abnormalities and are useful in making the diagnosis. These lesions rarely affect vision and do not require specific treatment [82].
The prevalence of ophthalmic features was described in a report of 100 TSC patients (median age 27, range 2 to 76 years) [83]. The following findings were noted:
●Retinal hamartomas were seen in 44 patients. These included a flat, translucent lesion, the most common type, in 31 (70 percent), a multilobular mulberry lesion (picture 9) in 24 (55 percent), and a transitional lesion with features of the two other types in four (9 percent). Calcification of the multilobular lesions results in the classic mulberry appearance.
●Punched-out areas of chorioretinal depigmentation (ie, retinal achromic patches) in the midperiphery of the retina were seen in 39 patients compared with only 6 of 100 controls.
●Nonretinal lesions included angiofibromas of the eyelids (in 39 of 100 patients), nonparalytic strabismus (in five), colobomas (in three), and sector iris depigmentation (in two).
●Among the refractive errors noted were myopia, hyperopia, and astigmatism >0.75 D in 27, 22, and 27 percent of eyes, respectively; these values are similar to those expected for the general population.
Oral and dental manifestations — TSC is associated with the development of intraoral fibromas, gingival hyperplasia, dental enamel pits, and deforming jaw bone cysts [84-87].
Cardiovascular manifestations — The characteristic cardiac feature of TSC is a rhabdomyoma, a benign tumor that often presents as multiple lesions. Cardiac rhabdomyomas are one of the most common pediatric cardiac tumors. (See "Cardiac tumors", section on 'Rhabdomyomas'.)
●Rhabdomyomas – Most infants and children who have cardiac rhabdomyomas have TSC [88]. However, rhabdomyomas are not a universal finding in children with TSC. In one longitudinal series of 125 patients with TSC, rhabdomyomas were found overall in 58 percent, including 61 percent of children ages 0 to 4, and 36 percent of children ages 5 to 18 [19]. Rhabdomyomas associated with TSC are typically multifocal. Occasionally, cardiac rhabdomyomas appear as an isolated finding in TSC [89].
Cardiac rhabdomyomas characteristically develop in utero and are often detected on prenatal ultrasound. In the longitudinal series of 125 patients with TSC, the finding of one or more rhabdomyomas before or soon after birth was the initial sign of TSC in 18 percent [19]. Although many rhabdomyomas are asymptomatic, patients with TSC and cardiac rhabdomyomas are most likely to be symptomatic in the newborn and early infancy period [82,90]. Thereafter, cardiac rhabdomyomas usually undergo spontaneous regression. The morbidity and mortality associated with these tumors reflect the potential for flow abnormalities if they grow to sufficient size to restrict blood flow. In one report that included 15 children with symptomatic cardiac rhabdomyoma (12 with TSC), the clinical presentation was heart failure or a cardiac murmur in six patients each and arrhythmia in three patients [90].
There is no evidence that cardiac rhabdomyomas undergo malignant transformation, and no treatment is necessary for asymptomatic tumors, particularly when first noted in an older child or adult with TSC. (See "Tuberous sclerosis complex: Management and prognosis", section on 'Cardiac involvement'.)
●Vascular pathologies – Coarctation of the aorta and constriction of major arteries (such as renal artery stenosis) are sometimes associated with TSC [82]. Aortic aneurysm may also occur [15].
Renal manifestations — Renal lesions are common among patients with TSC, and their prevalence increases with age. Angiomyolipomas are the most frequent renal manifestation of TSC. Less often, benign cysts, lymphangiomas, and renal cell carcinoma occur. Progressive enlargement of angiomyolipomas and hemorrhage into the lesion can result in pain and interfere with renal function. The risk of hemorrhage increases with size. Patients with tuberous sclerosis and renal lesions may have renin-dependent hypertension and are at risk of developing chronic kidney disease due to replacement and compression of the renal parenchyma. These issues are discussed in detail separately. (See "Renal manifestations of tuberous sclerosis complex".)
Pulmonary manifestations — Some adults with TSC develop pulmonary disease that is indistinguishable from the diffuse interstitial fibrosis known as lymphangioleiomyomatosis (LAM). This condition represents a cystic lung disease that can result in significant limitation in pulmonary function. The most common presenting features of LAM are dyspnea and pneumothorax. Among adults with TSC, the prevalence of LAM is higher for women than for men. The condition may worsen during pregnancy and can be a life-limiting complication of TSC.
LAM can occur as an isolated finding or can be associated with renal angiomyolipomas. As mentioned above, some women appear to have this combination as an isolated finding with no other features of TSC and no identifiable germline pathogenic variant in the TSC1 or TSC2 genes except in the LAM cells or angiomyolipoma.
The pulmonary manifestations of TSC and LAM are discussed in greater detail elsewhere. (See "Tuberous sclerosis complex associated lymphangioleiomyomatosis in adults" and "Sporadic lymphangioleiomyomatosis: Epidemiology and pathogenesis".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Tuberous sclerosis" and "Society guideline links: Lymphangioleiomyomatosis".)
SUMMARY AND RECOMMENDATIONS
●Genetics – The genetics and pathogenesis of TSC are reviewed separately. (See "Tuberous sclerosis complex: Genetics and pathogenesis".)
●Clinical features – TSC is characterized by a variety of benign tumors in multiple organs, including the brain, heart, skin, eyes, kidney, lung, and liver. There is also an increased risk of malignancy in TSC. (See 'Variable phenotype' above.)
•Brain lesions – Brain lesions characteristic of TSC include glioneuronal hamartomas, also called cortical tubers (image 1); white matter heterotopia; subependymal nodules (SENs) (image 2); and subependymal giant cell astrocytomas (SEGAs), which are also known as subependymal giant cell tumors (SGCTs) (image 3). (See 'Brain lesions' above.)
•Epilepsy – Most patients with TSC have epilepsy, and one-half or more have cognitive deficits and learning disabilities. Autism and autistic behaviors are common in children with TSC. (See 'Seizures and epilepsy' above and 'Intellectual disability' above and 'TSC-associated neuropsychiatric disorders (TAND)' above.)
•TSC-associated neuropsychiatric disorders (TAND) – Most patients with TSC have one or more of the disorders that make up TAND, which include intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, behavioral problems, psychiatric disorders, neuropsychologic deficits, school problems, and occupational difficulties. (See 'TSC-associated neuropsychiatric disorders (TAND)' above.)
•Skin lesions – Nearly all patients with TSC have one or more of the skin lesions that are characteristic of the disorder. The most common skin lesions in TSC are hypomelanotic macules (picture 2), angiofibromas (picture 5), shagreen patches (picture 8), and fibrous plaques (picture 4). (See 'Dermatologic manifestations' above.)
•Ophthalmic, cardiac, pulmonary, and renal manifestations – The characteristic cardiac feature of TSC is a rhabdomyoma. Angiomyolipomas are the most common renal manifestation of TSC. Benign cysts and lymphangiomas also can occur. Some adults with TSC develop pulmonary disease that is indistinguishable from the diffuse interstitial fibrosis known as lymphangioleiomyomatosis (LAM). Ophthalmic findings in TSC include both retinal and nonretinal abnormalities, although they rarely affect vision. (See 'Cardiovascular manifestations' above and 'Renal manifestations' above and 'Pulmonary manifestations' above and 'Ophthalmic manifestations' above.)
●Evaluation, diagnosis, and management – These aspects of TSC are reviewed separately. (See "Tuberous sclerosis complex: Evaluation and diagnosis" and "Tuberous sclerosis complex: Management and prognosis".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Sharon Plon, MD, PhD, James Owens, MD, PhD, and John B Bodensteiner, MD, who contributed to earlier versions of this topic review.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
