title: Intrauterine and postnatal growth failure with normal GH/IGF1 axis and insulin-resistant diabetes in a consanguineous kinship.
abstract: OBJECTIVE
  To describe the clinical and biochemical features, and perform molecular analysis for candidate abnormalities in a novel familial syndrome of intrauterine growth retardation (IUGR), failure of an adolescent growth spurt with proportional adult short stature, minimal subluxation of the 5th metacarpal-phalangeal joint, and adult-onset insulin-resistant diabetes unrelated to obesity or other manifestations of metabolic syndrome (MS).
  
  
  METHODS
  Detailed clinical history, auxological, biochemical, radiological, and molecular studies, including DNA analysis and in vitro study of the GH/IGF1 pathway.
  
  
  METHODS
  Ten affected adults from two generations of five related families were studied in detail, and information obtained about nine other likely affected individuals.
  
  
  RESULTS
  Height Z-scores ranged from -7.3 to -3.8. Unaffected parents of the older generation and frequency of confirmed and suspected instances of the syndrome in the two generations studied is consistent with autosomal recessive inheritance. Insulin resistance was uniformly present in seven subjects tested who were not taking insulin. Diabetes severity did not correlate with overweight. Subjects did not have other typical manifestations of MS such as substantial hyperlipidemia, osteoporosis, or hypertension. No biochemical abnormality in the GH/IGF1 axis or molecular defect was found.
  
  
  CONCLUSIONS
  While the association of IUGR and adult MS, including diabetes, has been well documented, these subjects did not have typical manifestations of MS. Abnormalities in common components that could result in a combination of IUGR, severe postnatal growth, and insulin resistance have been ruled out. A mutation in an unidentified gene may affect intrauterine and postnatal growth, with insulin resistance directly affected or as a result of this growth phenomenon.
authors.affiliation: Institute of Endocrinology, Metabolism, and Reproduction, Avenida Coruňa N26-191, 1337 y San Ignacio, Casilla 6337 CCI, Quito, Ecuador. jguevara@iemyr-ecuador.org
authors.forename: Jaime
authors.initials: J
authors.lastname: Guevara-Aguirre
authors.forename: Marco
authors.initials: M
authors.lastname: Guevara-Aguirre
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
authors.forename: Patricio
authors.initials: P
authors.lastname: Prócel
authors.forename: Jeannette
authors.initials: J
authors.lastname: Saavedra
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
authors.forename: Peng
authors.initials: P
authors.lastname: Fang
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
authors.forename: Sarah
authors.initials: S
authors.lastname: Kerns
authors.forename: Arlan L
authors.initials: AL
authors.lastname: Rosenbloom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D003241:Consanguinity; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D006130:Growth Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D019382:Human Growth Hormone / Q000097:blood / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I