RT Book, Section
A1 Krueger, Darcy A.
A1 Wusik, Katie
A1 Franz, David N.
A1 Schorry, Elizabeth K.
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102704177
T1 Tuberous Sclerosis Complex
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102704177
RD 2024/04/19
AB Disease  summary:Tuberous  sclerosis  complex  (TSC)  is  a  multiorgan  disorder  characterized  by  benign  growths  called  hamartomas  that  can  occur  anywhere  throughout  the  body.  Hypopigmented  macules,  facial  angiofibromas,  shagreen  patches,  ungual  fibromas,  and  dental  pitting  are  characteristic  of  the  disease.  Central  nervous  system  involvement  is  associated  with  highest  morbidity  and  clinically  manifests  as  epilepsy,  learning  disabilities  or  cognitive  impairment,  autism  and  other  behavioral  disorders,  psychiatric  disorders,  and  sleep  abnormalities.  The  hallmarks  of  cerebral  involvement  are  cortical  tubers,  subependymal  nodules  (SENs),  and  subependymal  giant  cell  astrocytomas  (SEGAs).  Angiomyolipomas  (AMLs)  of  the  kidney,  lymphangioleiomyomatosis  (LAM)  of  the  lung,  and  rhabdomyomas  of  the  heart  also  cause  significant  morbidity.Hereditary  basis:TSC  is  an  autosomal  dominant  genetic  disorder  with  near  100%  penetrance,  but  clinical  severity  is  highly  variable.  It  is  genetically  heterogeneous,  with  mutations  in  one  of  two  genes  (TSC1  or  TSC2)  causing  the  disorder.  About  one-third  of  cases  are  familial,  the  remainder  is  sporadic.  Genetic  mosaicism,  including  germline  mosaicism,  also  exists.  Genetic  testing  is  available  for  affected  individuals.  Mutation  in  either  gene  (TSC1,  TSC2)  is  detected  in  85%  of  cases.Differential  diagnosis:The  combination  of  multiple  features  of  TSC  is  rarely  mistaken  for  other  disorders.  However,  individual  features  may  overlap  with  those  of  other  syndromes.  Hypopigmented  macules  (ash  leaf  macules)  can  occur  from  many  different  etiologies;  vitiligo,  piebaldism,  hypomelanosis  of  Ito,  and  incontinentia  pigmenti  are  among  the  differential  diagnosis.  Renal  AMLs  and  pulmonary  LAM  can  occur  sporadically  but  certainly  occur  in  high  association  with  TSC.  Cortical  migration  defects  can  occur  as  an  isolated,  idiopathic  finding  unrelated  to  TSC.  Other  neurocutaneous  disorders,  such  as  neurofibromatosis  1  or  2,  have  distinct  skin  manifestations  and  tumor  types  which  should  not  be  mistaken  for  TSC.Management:Treatment  with  the  mammalian  target  of  rapamycin  (mTOR)  inhibitors  such  as  sirolimus  and  everolimus  results  in  significant  shrinking  of  SEGAs  and  renal  AMLs,  and  can  be  an  alternative  to  surgery  in  some  cases.  Benefit  in  lung  disease  (LAM)  has  also  been  demonstrated.  Additional  studies  are  ongoing  to  determine  their  efficacy  for  epilepsy  and  neurocognition  in  TSC.