TY  - CHAP
M1  - Book, Section
TI  - Adrenal Hypoplasias and Aplasias
A1  - McCabe, Edward R. B.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Adrenal  hypoplasia  congenita  (AHC)  has  an  estimated  incidence  of  1:12,500  live  births  and  two  distinct  histological  patterns  to  the  adrenal  cortices,  the  miniature  adult  and  cytomegalic  forms.In  the  miniature  adult  form  of  AHC,  the  small  amount  of  residual  adrenal  cortex  is  composed  primarily  of  permanent  adult  cortex  with  normal  structural  organization.  The  miniature  adult  form  is  either  sporadic  or  inherited  in  an  autosomal  recessive  manner,  and  is  frequently  associated  with  abnormal  central  nervous  system  development,  including  anencephaly  or  pituitary  gland  abnormalities.In  the  cytomegalic  form  of  AHC,  the  residual  adrenal  cortex  is  structurally  disorganized  with  scattered  irregular  nodular  formations  of  eosinophilic  cells,  with  the  adult  permanent  zone  absent  or  nearly  absent.  Enlarged  cells  are  present,  some  with  abundant  vacuolated  cytoplasm.  The  cytomegalic  form  is  generally  considered  to  be  X-linked,  but  there  may  be  one  or  more  autosomal  genes  associated  with  this  phenotype.X-linked  AHC  (MIM  300200)  is  caused  by  intragenic  mutations  or  complete  deletion  of  the  Xp21  DAX1  gene  (DSS-AHC  critical  region  on  the  X  chromosome,  gene  1).  Associated  with  deletion  of  DAX1,  the  Duchenne  muscular  dystrophy  (DMD)  and  glycerol  kinase  (GK)  genes  may  also  be  deleted  as  part  of  a  contiguous  gene  syndrome.  Patients  with  DAX1  mutations  have  adrenal  insufficiency  with  glucocorticoid  and  mineralocorticoid  deficiency,  and  hypogonadotropic  hypogonadism  (HH)  of  mixed  hypothalamic  and  pituitary  origin.  Gonadal  mosaicism  for  a  DAX1  mutation  has  been  reported  in  one  family  with  X-linked  AHC.DAX1  is  an  unusual  member  of  the  nuclear  hormone  receptor  superfamily  with  a  characteristic  C-terminal  putative  ligand-binding  domain  (LBD),  but  an  atypical  N-terminal  portion  that  is  a  DNA-binding  domain  (DBD)  in  the  typical  receptor.  Because  DAX1  has  the  structure  of  a  transcription  factor  and  maps  to  the  160  kb  critical  region  for  dosage  sensitive  sex  reversal  (DSS)  within  the  tandem  duplications  among  XY  individuals  with  female  or  ambiguous  genitalia,  it  is  a  candidate  gene  for  the  DSS  locus.  XY  transgenic  mice  with  overexpression  of  the  murine  homologue,  Dax1,  and  reduced  expression  of  SRY  (sex  determining  region,  Y  chromosome)  are  phenotypically  female.  These  observations  suggest  that  DAX1  may  be  the  hypothetical  X-linked  negative  regulator  of  male  gene  expression  that  is  antagonized  by  SRY  in  normal  XY  males.There  are  at  least  six  single-gene  disorders  associated  with  adrenal  hypoplasia/aplasia  that  have  definite  or  apparent  autosomal  recessive  inheritance:  ACTH  deficiency  (MIM  201400);  AHC  with  absent  pituitary  LH  (MIM  202150);  cytomegalic  form  of  AHC  with  autosomal  recessive  inheritance  (MIM  202155);  Pena-Shokeir  syndrome,  type  1  (MIM  208150);  holoprosencephaly  1,  alobar  (MIM  236100);  hypoadrenocorticism,  familial  (MIM  240200);  and  Meckel  syndrome  (MIM  249000).A  number  of  chromosomal  abnormalities  have  been  associated  with  adrenal  hypoplasia.  These  include  tetraploidy,  triploidy,  trisomy  18,  trisomy  21,  5p  duplication,  monosomy  7  and  the  11q−  syndrome.  Because  these  patients  frequently  have  central  nervous  system  abnormalities,  the  adrenal  hypoplasia  is  often  the  miniature  adult  form.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/23
UR  - ommbid.mhmedical.com/content.aspx?aid=1181454512
ER  -