This case represents de novo origin of two disorders that both may be parental-age related

Birth Defects Res A Clin Mol Teratol. 2010 Apr;88(4):228-31.

Co-occurrence of achondroplasia and Down syndrome: Genotype/phenotype association.
de Azevedo Moreira LM, Matos MA, Schiper PP, Carvalho AF, Gomes IC, Rolemberg JC, Ferreira de Lima RL, Toralles MB.

Laboratory of Human Genetics and Mutagenesis, Biology Institute, Federal University of Bahia, Barão de Geremoabo, Salvador, Bahia, Brazil. lazevedo@ufba.br

Abstract
BACKGROUND: This report describes the sixth case of an unusual association: Down syndrome with achondroplasia. It also analyzes the effects of both of these disorders on patient phenotype. METHODS: A male infant was evaluated for Down syndrome. His appearance also suggested a diagnosis of achondroplasia. The child was evaluated by physical examination, radiography, cytogenetic study, and mutation analysis. RESULTS: Chromosome analysis showed a karyotype of 47,XY,+21 in all 30 cells analyzed. Radiographic examination showed typical findings of achondroplasia, such as disproportionately large skull, shortening of limb segments, and lumbar lordosis. FGFR3 screening showed a heterozygous G1138A mutation. CONCLUSIONS: The interaction of these two distinct genetic disorders in the same patient produces a phenotype typical of each syndrome with some overlapping signs. This case represents de novo origin of two disorders that both may be parental-age related. (c) 2010 Wiley-Liss, Inc.

Missing heritability: paternal age effect mutations and selfish spermatogonia.

Nat Rev Genet. 2010 Aug;11(8):589.

Missing heritability: paternal age effect mutations and selfish spermatogonia.
Goriely A, Wilkie AO.

Anne Goriely and Andrew O.M. Wilkie are at the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

PMID: 20634812 [PubMed - in process]

Germline and somatic mosaicism for FGFR2 mutation in the mother of a child with Crouzon syndrome:

Am J Med Genet A. 2010 Jul 15. [Epub ahead of print]

Germline and somatic mosaicism for FGFR2 mutation in the mother of a child with Crouzon syndrome: Implications for genetic testing in "paternal age-effect" syndromes.
Goriely A, Lord H, Lim J, Johnson D, Lester T, Firth HV, Wilkie AO.

Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

Abstract
Crouzon syndrome is a dominantly inherited disorder characterized by craniosynostosis and facial dysostosis, caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene; it belongs to a class of disorders that mostly arise as de novo mutations and exhibit a near-exclusive paternal origin of mutation and elevated paternal age ("paternal age effect"). However, even if this is the major mode of origin of mutations in paternal age-effect disorders, germline mosaicism may also occur. Here we describe the first molecularly documented evidence of germline and somatic mosaicism for FGFR2 mutation, identified in the mother of a child with Crouzon syndrome caused by a heterozygous c.1007A>G (p.Asp336Gly) substitution. Levels of maternal somatic mosaicism for this mutation, estimated by pyrosequencing, ranged from 3.3% in hair roots to 14.1% in blood. Our observation underlines the importance of parental molecular testing for accurate genetic counseling of the risk of recurrence for Crouzon, and other paternal age-effect syndromes. (c) 2010 Wiley-Liss, Inc.

PMID: 20635358 [PubMed - as supplied by publisher]

Conclusions: This research reports the association between blood group system and macrosomia as well as parental age and GDM simultaneously.

Pediatr Int. 2010 Jul 4. [Epub ahead of print]

MACROSOMIA, TOP OF THE ICEBERG: THE CHARM OF UNDERLYING FACTORS.
Donma MM.

DEPARTMENT OF NEONATOLOGY UNIT, PEDIATRICS CLINICS, MINISTRY OF HEALTH, SULEYMANIYE MATERNITY AND CHILDREN'S DISEASES EDUCATION AND RESEARCH HOSPITAL, ISTANBUL, TURKEY.

Abstract
Background: Macrosomia is associated with childhood obesity. Gestational diabetes mellitus(GDM) is a risk factor for macrosomia. The aim of this large scaled investigation is to determine the incidence, risk factors, characteristic features, and perinatal outcome of macrosomic infants. Methods: This prospective study was carried out on 6,385 newborns. Demographic data included maternal age, paternal age, type of delivery, sex, parity and gestational age at delivery. Anthropometric measurements were recorded. ABO/Rh typing was performed and GDM was diagnosed. Results: Out of 6,385 term deliveries, 477 infants(7.47%) were macrosomic. Incidence of GDM was 0.6% and 4.8% in control group and among macrosomic births, respectively. Incidence of GDM(+) cases was 4% among macrosomic infants weighing 4000 g. < n < 4500 g. GDM(+) cases were densely populated(11%), among macrosomic infants weighing >/=4500 g.(p /=4500 g. than those weighing 4000 g. < n < 4500 g.(p
PMID: 20626633 [PubMed - as supplied by publisher]