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Tuberous sclerosis 1(TSC1)

MedGen UID:
344288
Concept ID:
C1854465
Disease or Syndrome
Synonym: TSC1
 
Gene (location): TSC1 (9q34.13)
 
Monarch Initiative: MONDO:0008612
OMIM®: 191100

Disease characteristics

Excerpted from the GeneReview: Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical tubers, and subependymal giant cell astrocytomas [SEGAs], seizures, TSC-associated neuropsychiatric disorder [TAND]); kidneys (benign renal angiomyolipomas, epithelial cysts, oncocytoma, renal cell carcinoma); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system-related problems (including TAND) are the leading cause of morbidity, whereas kidney disease is the leading cause of mortality. [from GeneReviews]
Authors:
Hope Northrup  |  Mary Kay Koenig  |  Deborah A Pearson, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the brain, kidneys, heart, skin, and other organs, in some cases leading to significant health problems. Tuberous sclerosis complex also causes developmental problems, and the signs and symptoms of the condition vary from person to person.

Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face called facial angiofibromas are also common beginning in childhood. Sometimes, affected individuals have areas of bone or dental damage.

Tuberous sclerosis complex often affects the brain, with some affected individuals having benign growths in the outer surface of the brain (cerebral cortex) known as cortical tubers. Individuals with tuberous sclerosis complex often develop a pattern of behaviors called TSC-associated neuropsychiatric disorders (TAND). These disorders include hyperactivity, aggression, psychiatric conditions, intellectual disability, and problems with communication and social interaction (autism spectrum disorder). Additionally, individuals with tuberous sclerosis complex may have attention-deficit/hyperactivity disorder (ADHD) or seizures.

Kidney tumors are common in people with tuberous sclerosis complex; these growths can cause severe problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart (cardiac rhabdomyoma) and the light-sensitive tissue at the back of the eye (the retina). Some women with tuberous sclerosis complex develop lymphangioleiomyomatosis (LAM), which is a lung disease characterized by the abnormal overgrowth of smooth muscle-like tissue in the lungs that causes coughing, shortness of breath, chest pain, and lung collapse.  https://medlineplus.gov/genetics/condition/tuberous-sclerosis-complex

Clinical features

From HPO
Renal cell carcinoma
MedGen UID:
766
Concept ID:
C0007134
Neoplastic Process
A type of carcinoma of the kidney with origin in the epithelium of the proximal convoluted renal tubule.
Gingival fibromatosis
MedGen UID:
42017
Concept ID:
C0016049
Finding
The presence of fibrosis of the gingiva.
Angiofibromas
MedGen UID:
104928
Concept ID:
C0206731
Neoplastic Process
Angiofibroma consist of many often dilated vessels.
Pulmonary lymphangiomyomatosis
MedGen UID:
852455
Concept ID:
C0238399
Finding
Infiltration of smooth muscle-like cells in lymph vessels as well as the lung (pleura, alveolar septa, bronchi, pulmonary vessels and lymphatics as well as lymph nodes, especially in posterior mediastinum and retroperitoneum). Focal emphysema can develop because of airway narrowing, and the thoracic duct may be obliterated. Pulmonary lymphangiomyomatosis may lead to multiple small cysts with a hamartomatous proliferation of smooth muscle in their walls.
Kidney angiomyolipoma
MedGen UID:
69146
Concept ID:
C0241961
Neoplastic Process
A benign renal neoplasm composed of fat, vascular, and smooth muscle elements.
Subungual fibromas
MedGen UID:
82726
Concept ID:
C0266003
Finding
The presence of fibromata beneath finger or toenails.
Cardiac rhabdomyoma
MedGen UID:
232027
Concept ID:
C1332852
Neoplastic Process
A benign tumor of cardiac striated muscle.
Renal cyst
MedGen UID:
854361
Concept ID:
C3887499
Disease or Syndrome
A fluid filled sac in the kidney.
Wolff-Parkinson-White pattern
MedGen UID:
12162
Concept ID:
C0043202
Disease or Syndrome
Wolff-Parkinson-White syndrome is a condition characterized by abnormal electrical pathways in the heart that cause a disruption of the heart's normal rhythm (arrhythmia).\n\nThe heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. A specialized cluster of cells called the atrioventricular node conducts electrical impulses from the heart's upper chambers (the atria) to the lower chambers (the ventricles). Impulses move through the atrioventricular node during each heartbeat, stimulating the ventricles to contract slightly later than the atria.\n\nPeople with Wolff-Parkinson-White syndrome are born with an extra connection in the heart, called an accessory pathway, that allows electrical signals to bypass the atrioventricular node and move from the atria to the ventricles faster than usual. The accessory pathway may also transmit electrical impulses abnormally from the ventricles back to the atria. This extra connection can disrupt the coordinated movement of electrical signals through the heart, leading to an abnormally fast heartbeat (tachycardia) and other changes in heart rhythm. Resulting symptoms include dizziness, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, and fainting (syncope). In rare cases, arrhythmias associated with Wolff-Parkinson-White syndrome can lead to cardiac arrest and sudden death. The most common arrhythmia associated with Wolff-Parkinson-White syndrome is called paroxysmal supraventricular tachycardia.\n\nComplications of Wolff-Parkinson-White syndrome can occur at any age, although some individuals born with an accessory pathway in the heart never experience any health problems associated with the condition.\n\nWolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. The most common heart defect associated with the condition is Ebstein anomaly, which affects the valve that allows blood to flow from the right atrium to the right ventricle (the tricuspid valve). Additionally, the heart rhythm problems associated with Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe disease (a disorder characterized by the storage of excess glycogen), Danon disease (a condition that weakens the heart and skeletal muscles and causes intellectual disability), and tuberous sclerosis complex (a condition that results in the growth of noncancerous tumors in many parts of the body).
Astrocytoma
MedGen UID:
438
Concept ID:
C0004114
Neoplastic Process
Astrocytoma is a neoplasm of the central nervous system derived from astrocytes. Astrocytes are a type of glial cell, and thus astrocytoma is a subtype of glioma.
Autism
MedGen UID:
13966
Concept ID:
C0004352
Mental or Behavioral Dysfunction
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Ependymoma
MedGen UID:
41825
Concept ID:
C0014474
Neoplastic Process
The presence of an ependymoma of the central nervous system.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Optic nerve glioma
MedGen UID:
138056
Concept ID:
C0346326
Neoplastic Process
A glioma originating in the optic nerve or optic chiasm.
Hemimegalencephaly
MedGen UID:
140910
Concept ID:
C0431391
Finding
Enlargement of all or parts of one cerebral hemisphere.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Epileptic spasm
MedGen UID:
315948
Concept ID:
C1527366
Disease or Syndrome
A sudden flexion, extension, or mixed extension-flexion of predominantly proximal and truncal muscles that is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure. Limited forms may occur
Subependymal nodules
MedGen UID:
369895
Concept ID:
C1968958
Finding
Small nodular masses which originate in the subependymal region of the lateral ventricles and protrude into the ventricular cavity. They may represent subependymal hamartomas of tuberous sclerosis.
Cortical tubers
MedGen UID:
369896
Concept ID:
C1968959
Finding
Cortical tubers in the brain are hamartomatous lesions typically located at the gray-white matter interface, commonly in the frontal and parietal lobes. Cortical tubers are composed of abnormal glial and neural cells, and the size, number, and location vary among patients.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Chordoma
MedGen UID:
40277
Concept ID:
C0008487
Neoplastic Process
Chordomas are rare, clinically malignant tumors derived from notochordal remnants. They occur along the length of the spinal axis, predominantly in the sphenooccipital, vertebral, and sacrococcygeal regions. They are characterized by slow growth, local destruction of bone, extension into adjacent soft tissues, and, rarely, distant metastatic spread (Stepanek et al., 1998). The incidence of chordoma is age-dependent, with fewer than 5% occurring in children and adolescents (summary by McMaster et al., 2011).
Cerebral calcification
MedGen UID:
124360
Concept ID:
C0270685
Finding
The presence of calcium deposition within the cerebrum.
Dental enamel pits
MedGen UID:
395958
Concept ID:
C1860711
Finding
The presence of small depressions in the dental enamel.
Adenoma sebaceum
MedGen UID:
75563
Concept ID:
C0265319
Neoplastic Process
The presence of a sebaceous adenoma with origin in the sebum secreting cells of the skin.
Preauricular hair displacement
MedGen UID:
869865
Concept ID:
C4024296
Finding
An tongue-like extension of hair towards the cheeks, in which hair growth extends in front of the ear to the lateral cheekbones.
Subcutaneous nodule
MedGen UID:
101803
Concept ID:
C0151811
Pathologic Function
Slightly elevated lesions on or in the skin with a diameter of over 5 mm.
Cafe-au-lait spot
MedGen UID:
113157
Concept ID:
C0221263
Finding
Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children.
Shagreen patch
MedGen UID:
96599
Concept ID:
C0432363
Congenital Abnormality
A plaque representing a connective-tissue nevus. Connective tissue naevi are uncommon skin lesions that occur when the deeper layers of the skin do not develop correctly or the components of these layers occur in the wrong proportion. Shagreen patches are oval-shaped and nevoid, skin-colored or occasionally pigmented, smooth or crinkled. The word shagreen refers to a type of roughened untanned leather.
Hypomelanotic macule
MedGen UID:
869790
Concept ID:
C4024220
Finding
Hypomelanotic macules ("ash leaf spots") are white or lighter patches of skin that may appear anywhere on the body and are caused by a lack of melanin. White ash leaf-shaped macules are considered to be characteristic of tuberous sclerosis.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Precocious puberty
MedGen UID:
18752
Concept ID:
C0034013
Disease or Syndrome
The onset of secondary sexual characteristics before a normal age. Although it is difficult to define normal age ranges because of the marked variation with which puberty begins in normal children, precocious puberty can be defined as the onset of puberty before the age of 8 years in girls or 9 years in boys.
Achromatic retinal patches
MedGen UID:
348171
Concept ID:
C1860710
Finding
Areas of the retina lacking pigmentation. Punched out areas of chorioretinal hypopigmentation less than 1 disk diameter in size and tending to be located in the midperiphery of the retina.
Retinal hamartoma
MedGen UID:
354977
Concept ID:
C1863411
Neoplastic Process
A hamartoma (a benign, focal malformation consisting of a disorganized mixture of cells and tissues) of the retina.
Premature chromatid separation
MedGen UID:
867516
Concept ID:
C4021899
Cell or Molecular Dysfunction
The presence of premature sister chromatid segregation.

Term Hierarchy

Professional guidelines

PubMed

Delanty N, Mohanraj R, Shankar R, Wehner T, Stephen LJ, D'Souza W, Cappucci S, McMurray R, Sainz-Fuertes R, Villanueva V
Epilepsy Res 2024 May;202:107339. Epub 2024 Mar 2 doi: 10.1016/j.eplepsyres.2024.107339. PMID: 38492461
Kohrman MH
Pediatr Neurol 2012 May;46(5):267-75. doi: 10.1016/j.pediatrneurol.2012.02.015. PMID: 22520346
Schillinger F, Montagnac R
Nephrol Dial Transplant 1996 Mar;11(3):481-5. PMID: 8671819

Curated

Orphanet, Tuberous sclerosis, 2007

Recent clinical studies

Therapy

Purcaro C, Marramiero L, Santangelo C, Bondi D, Di Filippo ES
Eur J Appl Physiol 2024 Aug;124(8):2227-2233. Epub 2024 May 28 doi: 10.1007/s00421-024-05515-1. PMID: 38806941Free PMC Article
Huang Q, Li F, Hu H, Fang Z, Gao Z, Xia G, Ng WL, Khodadadi-Jamayran A, Chen T, Deng J, Zhang H, Almonte C, Labbe K, Han H, Geng K, Tang S, Freeman GJ, Li Y, Chen H, Wong KK
Sci Adv 2022 Feb 4;8(5):eabi9533. doi: 10.1126/sciadv.abi9533. PMID: 35119931Free PMC Article
Ryu JS, Lim JH, Kim HJ, Kim MJ, Park MH, Kim JS
Biosci Rep 2019 Mar 29;39(3) Epub 2019 Mar 19 doi: 10.1042/BSR20181426. PMID: 30842342Free PMC Article
Luo J
Autophagy 2014;10(12):2099-108. doi: 10.4161/15548627.2014.981916. PMID: 25484085Free PMC Article
Shamberger RC, Welch KJ
J Pediatr Surg 1988 Jul;23(7):615-22. doi: 10.1016/s0022-3468(88)80629-8. PMID: 3204460

Prognosis

Purcaro C, Marramiero L, Santangelo C, Bondi D, Di Filippo ES
Eur J Appl Physiol 2024 Aug;124(8):2227-2233. Epub 2024 May 28 doi: 10.1007/s00421-024-05515-1. PMID: 38806941Free PMC Article
Lin Q, Wang X, Han T, Zhou X
BMC Med Genomics 2023 Nov 21;16(1):299. doi: 10.1186/s12920-023-01738-x. PMID: 37990318Free PMC Article
Patil P, Pencheva BB, Patil VM, Fangusaro J
Neurotherapeutics 2022 Oct;19(6):1752-1771. Epub 2022 Sep 2 doi: 10.1007/s13311-022-01277-w. PMID: 36056180Free PMC Article
Li YL, Zhang MM, Wu LW, Liu YH, Zhang ZY, Zeng LH, Lin NM, Zhang C
J Biomed Sci 2022 Jun 2;29(1):34. doi: 10.1186/s12929-022-00817-y. PMID: 35655269Free PMC Article
Tang H, Fang T, Ji M, Wang JP, Song LL, Zhang QY, Wu JS
Biochem Biophys Res Commun 2021 Nov 12;578:7-14. Epub 2021 Sep 6 doi: 10.1016/j.bbrc.2021.08.057. PMID: 34520980

Clinical prediction guides

Purcaro C, Marramiero L, Santangelo C, Bondi D, Di Filippo ES
Eur J Appl Physiol 2024 Aug;124(8):2227-2233. Epub 2024 May 28 doi: 10.1007/s00421-024-05515-1. PMID: 38806941Free PMC Article
Lin Q, Wang X, Han T, Zhou X
BMC Med Genomics 2023 Nov 21;16(1):299. doi: 10.1186/s12920-023-01738-x. PMID: 37990318Free PMC Article
Patil P, Pencheva BB, Patil VM, Fangusaro J
Neurotherapeutics 2022 Oct;19(6):1752-1771. Epub 2022 Sep 2 doi: 10.1007/s13311-022-01277-w. PMID: 36056180Free PMC Article
Ryu JS, Lim JH, Kim HJ, Kim MJ, Park MH, Kim JS
Biosci Rep 2019 Mar 29;39(3) Epub 2019 Mar 19 doi: 10.1042/BSR20181426. PMID: 30842342Free PMC Article
Luo J
Autophagy 2014;10(12):2099-108. doi: 10.4161/15548627.2014.981916. PMID: 25484085Free PMC Article

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