title: Intrafamilial Phenotypic Variability and Consequences of Non-Compliance with Treatment in Congenital Adrenal Hyperplasia and Congenital Hypothyroidism within a Single Family .
abstract: BACKGROUND
  Coexistence of congenital adrenal hyperplasia (CAH) and congenital hypothyroidism (CH) due to TG mutation in the same non-consanguineous family is rare.
  
  
  METHODS
  We report 4 siblings born to unrelated parents, the father being an asymptomatic carrier of homozygous p.V281L and heterozygous p.I172N CYP21A2 mutations. Sibling 1 had salt-wasting CAH (CYP21A2 genotype Intron 2 splice/p.I172N and p.V281L). She also had CH (TG genotype p.R296/ p.T1416Rfs*30) and learning difficulties. Poor compliance and morbid obesity resulted in short stature, precocious puberty, hirsutism, amenorrhoea, insulin insensitivity and a possible adrenal adenoma. Sibling 3 (CYP21A2 and TG genotype similar to sibling 1) is a boy presenting with salt-wasting CAH, CH, and developmental delay. He was overweight and underwent precocious puberty. Although siblings 2 and 4 (both females) share the same CYP21A2 genotype (Intron 2 splice/p.V281L), the former only had biochemical evidence of CAH, while the latter presented at 9.8 years of age with a history of pubarche at 7 years and advanced bone age.
  
  
  CONCLUSIONS
  We report the unusual occurrence of 2 rare autosomal recessive diseases, CAH and CH. Our cases highlight the phenotypic variability of CAH and CH due to TG mutations, even within a single family, and illustrate the importance of optimal disease control. .
authors.affiliation: Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom.|Department of Medical Translational Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Improda
authors.affiliation: Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ponmani
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Nadia
authors.initials: N
authors.lastname: Schoenmakers
authors.affiliation: Department of Paediatric Endocrinology, Alder Hey Children's Hospital, Liverpool, United Kingdom.
authors.forename: Senthil
authors.initials: S
authors.lastname: Senniappan
authors.affiliation: Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Abigail
authors.initials: A
authors.lastname: Atterbury
authors.affiliation: Department of Clinical Genetics, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Barnicoat
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Krishna
authors.initials: K
authors.lastname: Chatterjee
authors.affiliation: Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom.|Developmental Endocrinology Research Group, Section of Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Mehul T
authors.initials: MT
authors.lastname: Dattani
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D003409:Congenital Hypothyroidism / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010349:Patient Compliance; D010375:Pedigree; D010641:Phenotype; D013954:Thyroglobulin / Q000235:genetics*
chemical_list: D013954:Thyroglobulin
keywords: 21-Hydroxylase; Adrenal adenoma; Developmental delay ; Thyroglobulin