title: Macrocephaly associated with the DICER1 syndrome.
abstract: Germ-line mutations in DICER1 increase the risk of various tumors, including pleuropulmonary blastoma. Macrocephaly and symmetric overgrowth have been reported in some, but not all, patients with mosaic DICER1 RNase IIIb mutations. The prevalence of these features in individuals with constitutional germ-line DICER1 mutations is unknown.
  
  
  
  We analyzed prospectively collected auxology data from 67 DICER1 mutation carriers and 43 family controls. We assessed differences between groups using an exact test for proportions and generalized estimating equations for continuous dependent variables.
  
  
  
  Twenty-eight DICER1 mutation carriers (42%) were macrocephalic, and none had an occipitofrontal circumference (OFC) below the third centile, which significantly differed from family controls, of whom five were macrocephalic (12%) and two had OFC below the third centile (5%) (P < 0.001). DICER1 mutation carriers were taller than familial controls after controlling for gender (P = 0.048), but similar proportions of both groups were above the 97th centile of population norms. Head circumference remained increased after adjusting for differences in height.
  
  
  
  For the first time, we establish macrocephaly as a common finding in the DICER1 syndrome. Like some other tumor-predisposition disorders, macrocephaly may be a useful, albeit a subtle, clinical clue to the DICER1 syndrome diagnosis.Genet Med 19 2, 244-248.
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Khan
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Andrew J
authors.identifier: 0000-0002-3952-881X
authors.initials: AJ
authors.lastname: Bauer
authors.affiliation: Children's National Medical Center, Washington, DC, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Doros
authors.affiliation: Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA.|International Pleuropulmonary Blastoma Registry, Minneapolis, Minnesota, USA.|International Ovarian and Testicular Stromal Tumor Registry, Minneapolis, Minnesota, USA.
authors.forename: Kris Ann P
authors.identifier: 0000-0002-1788-5832
authors.initials: KA
authors.lastname: Schultz
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
authors.forename: Rosamma M
authors.initials: RM
authors.lastname: Decastro
authors.affiliation: Westat Inc., Rockville, Maryland, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Harney
authors.affiliation: Westat Inc., Rockville, Maryland, USA.
authors.forename: Ron G
authors.initials: RG
authors.lastname: Kase
authors.affiliation: Westat Inc., Rockville, Maryland, USA.
authors.forename: Ann G
authors.identifier: 0000-0003-2164-4158
authors.initials: AG
authors.lastname: Carr
authors.affiliation: Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA.|International Pleuropulmonary Blastoma Registry, Minneapolis, Minnesota, USA.|International Ovarian and Testicular Stromal Tumor Registry, Minneapolis, Minnesota, USA.
authors.forename: Anne K
authors.identifier: 0000-0002-3371-3096
authors.initials: AK
authors.lastname: Harris
authors.affiliation: Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA.|International Pleuropulmonary Blastoma Registry, Minneapolis, Minnesota, USA.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Williams
authors.affiliation: Washington University, St. Louis, Missouri, USA.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Dehner
authors.affiliation: Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA.|International Pleuropulmonary Blastoma Registry, Minneapolis, Minnesota, USA.
authors.forename: Yoav H
authors.identifier: 0000-0001-7990-1802
authors.initials: YH
authors.lastname: Messinger
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001827:Body Height / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D058627:Megalencephaly / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018202:Pulmonary Blastoma / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D043244:Ribonuclease III / Q000235:genetics*
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases