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Tuberous sclerosis 2(TSC2)

MedGen UID:
348170
Concept ID:
C1860707
Disease or Syndrome
Synonyms: TSC2
Modes of inheritance:
Heterogeneous
MedGen UID:
67020
Concept ID:
C0242960
Organism Attribute
Source: HPO
The production of the same or similar phenotypes (observed biochemical, physiological, and morphological characteristics of a person determined by his/her genotype) by different genetic mechanisms. There are two types: (1) allelic heterogeneity - when different alleles at a locus can produce variable expression of a condition; and (2) locus heterogeneity - the term used to describe disease in which mutations at different loci can produce the same disease phenotype.
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Genes (locations): IFNG (12q15); TSC2 (16p13.3)
OMIM®: 613254

Definition

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems, including the brain, skin, heart, kidneys, and lung. These changes can result in epilepsy, learning difficulties, behavioral problems, and renal failure, among other complications (reviews by Crino et al., 2006 and Curatolo et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of tuberous sclerosis, see tuberous sclerosis-1 (191100), caused by mutation in the TSC1 gene (605284) on chromosome 9q34. Approximately 10 to 30% of cases of tuberous sclerosis are due to mutations in the TSC1 gene: the frequency of cases due to mutations in the TSC2 gene is consistently higher. TSC2 mutations are associated with more severe disease (Crino et al., 2006) (see GENOTYPE/PHENOTYPE CORRELATIONS section). [from OMIM]

Additional description

From GHR
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 skin, brain, kidneys, 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.Tuberous sclerosis complex often affects the brain, causing seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems. Some affected children have the characteristic features of autism, a developmental disorder that affects communication and social interaction. Benign brain tumors can also develop in people with tuberous sclerosis complex; these tumors can cause serious or life-threatening complications.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, lungs, and the light-sensitive tissue at the back of the eye (the retina).  https://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex

Clinical features

Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Your thyroid is a butterfly-shaped gland in your neck, just above your collarbone. It is one of your endocrine glands, which make hormones. Thyroid hormones control the rate of many activities in your body. These include how fast you burn calories and how fast your heart beats. All of these activities are your body's metabolism. If your thyroid gland is not active enough, it does not make enough thyroid hormone to meet your body's needs. This condition is hypothyroidism. Hypothyroidism is more common in women, people with other thyroid problems, and those over 60 years old. Hashimoto's disease, an autoimmune disorder, is the most common cause. Other causes include thyroid nodules, thyroiditis, congenital hypothyroidism, surgical removal of part or all of the thyroid, radiation treatment of the thyroid, and some medicines. The symptoms can vary from person to person. They may include. -Fatigue. -Weight gain. -A puffy face. -Cold intolerance. -Joint and muscle pain. -Constipation. -Dry skin. -Dry, thinning hair. -Decreased sweating. -Heavy or irregular menstrual periods and fertility problems. -Depression. -Slowed heart rate. To diagnose hypothyroidism, your doctor will look at your symptoms and blood tests. Treatment is with synthetic thyroid hormone, taken every day. NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
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.
Cardiac rhabdomyoma
MedGen UID:
232027
Concept ID:
C1332852
Neoplastic Process
A benign tumor of cardiac striated muscle.
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 brain structures.
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.
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.

Term Hierarchy

Professional guidelines

PubMed

ACMG Board of Directors.
Genet Med 2015 Jan;17(1):68-9. Epub 2014 Nov 13 doi: 10.1038/gim.2014.151. PMID: 25356965
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics.
Genet Med 2013 Jul;15(7):565-74. Epub 2013 Jun 20 doi: 10.1038/gim.2013.73. PMID: 23788249Free PMC Article
Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee.
Genet Med 2013 May;15(5):399-407. Epub 2013 Mar 21 doi: 10.1038/gim.2013.32. PMID: 23519317

External

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

Orphanet, Tuberous sclerosis, 2007

Recent clinical studies

Etiology

Yamanaka S, Mizobuchi T, Kurihara M
Ann Thorac Cardiovasc Surg 2017 Feb 20;23(1):36-39. Epub 2016 Jun 27 doi: 10.5761/atcs.cr.16-00095. PMID: 27349306Free PMC Article
Cristescu M, Abel EJ, Wells S, Ziemlewicz TJ, Hedican SP, Lubner MG, Hinshaw JL, Brace CL, Lee FT Jr
Cardiovasc Intervent Radiol 2016 Mar;39(3):433-40. Epub 2015 Sep 21 doi: 10.1007/s00270-015-1201-5. PMID: 26390876
Zeglam AM, Al-Ogab MF, Al-Shaftery T
Acta Neurol Belg 2015 Sep;115(3):351-4. Epub 2014 Oct 26 doi: 10.1007/s13760-014-0384-x. PMID: 25344829
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Diagnosis

Cinalli G, Imperato A, Mirone G, Di Martino G, Nicosia G, Ruggiero C, Aliberti F, Spennato P
J Neurosurg Pediatr 2017 Mar;19(3):325-332. Epub 2017 Jan 13 doi: 10.3171/2016.10.PEDS16352. PMID: 28084922
Yamanaka S, Mizobuchi T, Kurihara M
Ann Thorac Cardiovasc Surg 2017 Feb 20;23(1):36-39. Epub 2016 Jun 27 doi: 10.5761/atcs.cr.16-00095. PMID: 27349306Free PMC Article
Prayson RA
J Clin Neurosci 2016 Sep;31:35-6. Epub 2016 May 9 doi: 10.1016/j.jocn.2016.03.003. PMID: 27174083
Zeglam AM, Al-Ogab MF, Al-Shaftery T
Acta Neurol Belg 2015 Sep;115(3):351-4. Epub 2014 Oct 26 doi: 10.1007/s13760-014-0384-x. PMID: 25344829
Hernández-Breijo B, Monserrat J, Román ID, González-Rodríguez Á, Fernández-Moreno MD, Lobo MV, Valverde ÁM, Gisbert JP, Guijarro LG
Toxicol Appl Pharmacol 2013 Nov 1;272(3):568-78. Epub 2013 Aug 16 doi: 10.1016/j.taap.2013.07.024. PMID: 23958494

Therapy

Yamanaka S, Mizobuchi T, Kurihara M
Ann Thorac Cardiovasc Surg 2017 Feb 20;23(1):36-39. Epub 2016 Jun 27 doi: 10.5761/atcs.cr.16-00095. PMID: 27349306Free PMC Article
Cristescu M, Abel EJ, Wells S, Ziemlewicz TJ, Hedican SP, Lubner MG, Hinshaw JL, Brace CL, Lee FT Jr
Cardiovasc Intervent Radiol 2016 Mar;39(3):433-40. Epub 2015 Sep 21 doi: 10.1007/s00270-015-1201-5. PMID: 26390876
Hernández-Breijo B, Monserrat J, Román ID, González-Rodríguez Á, Fernández-Moreno MD, Lobo MV, Valverde ÁM, Gisbert JP, Guijarro LG
Toxicol Appl Pharmacol 2013 Nov 1;272(3):568-78. Epub 2013 Aug 16 doi: 10.1016/j.taap.2013.07.024. PMID: 23958494
Riikonen R
J Child Neurol 2004 Jun;19(6):401-4. doi: 10.1177/088307380401900601. PMID: 15446386
Astrinidis A, Kouvatsi A, Nahmias J, Povey S, Pandeliadis C, Danzaki A, Schneider M, Triantaphyllidis C
Hum Mutat 1998;12(3):217. PMID: 10660335

Prognosis

Yamanaka S, Mizobuchi T, Kurihara M
Ann Thorac Cardiovasc Surg 2017 Feb 20;23(1):36-39. Epub 2016 Jun 27 doi: 10.5761/atcs.cr.16-00095. PMID: 27349306Free PMC Article
Back SJ, Andronikou S, Kilborn T, Kaplan BS, Darge K
Pediatr Radiol 2015 Mar;45(3):386-95. Epub 2014 Oct 30 doi: 10.1007/s00247-014-3147-1. PMID: 25355409
Maheshwar MM, Sandford R, Nellist M, Cheadle JP, Sgotto B, Vaudin M, Sampson JR
Hum Mol Genet 1996 Jan;5(1):131-7. PMID: 8789450
Geist RT, Gutmann DH
Cell Growth Differ 1995 Nov;6(11):1477-83. PMID: 8562486
Xu L, Sterner C, Maheshwar MM, Wilson PJ, Nellist M, Short PM, Haines JL, Sampson JR, Ramesh V
Genomics 1995 Jun 10;27(3):475-80. doi: 10.1006/geno.1995.1079. PMID: 7558029

Clinical prediction guides

Cai S, Everitt JI, Kugo H, Cook J, Kleymenova E, Walker CL
Am J Pathol 2003 Feb;162(2):457-68. doi: 10.1016/S0002-9440(10)63840-0. PMID: 12547704Free PMC Article
Astrinidis A, Kouvatsi A, Nahmias J, Povey S, Pandeliadis C, Danzaki A, Schneider M, Triantaphyllidis C
Hum Mutat 1998;12(3):217. PMID: 10660335
Kerfoot C, Wienecke R, Menchine M, Emelin J, Maize JC Jr, Welsh CT, Norman MG, DeClue JE, Vinters HV
Brain Pathol 1996 Oct;6(4):367-75. PMID: 8944308
Maheshwar MM, Sandford R, Nellist M, Cheadle JP, Sgotto B, Vaudin M, Sampson JR
Hum Mol Genet 1996 Jan;5(1):131-7. PMID: 8789450
Xu L, Sterner C, Maheshwar MM, Wilson PJ, Nellist M, Short PM, Haines JL, Sampson JR, Ramesh V
Genomics 1995 Jun 10;27(3):475-80. doi: 10.1006/geno.1995.1079. PMID: 7558029

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