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Genetic and environmental factors in the aetiology of hypospadias

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Abstract

This article reviews the current evidence and knowledge of the aetiology of hypospadias. Hypospadias remains a fascinating anomaly of the male phallus. It may be an isolated occurrence or part of a syndrome or field defect. The increasing use of assisted reproductive techniques and hormonal manipulation during pregnancy may have been associated with an apparent rise in the incidence of hypospadias. Genetic studies and gene analysis have suggested some defects that could result in hypospadias. New light has also been thrown on environmental factors that could modulate candidate genes, causing altered development of the male external genitalia.

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Abbreviations

ART:

Assisted reproductive technology

ATF3:

Activating transcription factor

BMI:

Body mass index

BMP7:

Bone morphogenic protein

DDE:

p p’ Dichloro diphenyl dichloroethane

DDT:

p p’Dichloro diphenyl trichloroethane

DES:

Diethylstilbestrol

DGKK:

Diacylglycerol kinase kappa

DHCR:

Dihydrocholesterol reductase

EDC:

Endocrine disrupting chemicals

ESR1:

Oestrogen receptor 1

ESR2:

Oestrogen receptor 2

FGFR2:

Fibroblast growth factor

FGF8:

Fibroblast growth factor

FGF10:

Fibroblast growth factor

GWAS:

Genome-wide association study

GXE:

Gene environment interactions

HCB:

Hexachlorobenzene

HCG:

Human chorionic gonadotrophin

HOXA13:

Homeobox A 13

ICSI:

Intracytoplasmic sperm injection

IUGR:

Intrauterine growth retardation

IVF:

In vitro fertilisation

LBW:

Low birth weight

MAMLD1:

Mastermind-like domain containing 1

SF 1:

Splicing factor 1

SGA:

Small for gestational age

SNP:

Single nucleotide polymorphisms

SOX9:

SRY box 9

SRD5A2:

Steroid 5 alpha reductase

SRY gene:

Sex-determining region Y

WT1:

Wilms tumour 1

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Authors and Affiliations

  1. Douglas Cohen Department of Paediatric Surgery, The Children’s Hospital at Westmead, Discipline of Paediatrics and Child Health, Sydney Medical School, The University of Sydney, Locked Bag 4001, Westmead, NSW, 2145, Australia

    Mathew George & Andrew J. A. Holland

  2. Northern Clinical School, Kolling Institute of Medical Research, The University of Sydney, Reserve Road, St Leonards, NSW, 2065, Australia

    Francisco J. Schneuer

  3. Telethon Kids Institute, University of Western Australia, Perth, WA, 6009, Australia

    Sarra E. Jamieson

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George, M., Schneuer, F.J., Jamieson, S.E. et al. Genetic and environmental factors in the aetiology of hypospadias. Pediatr Surg Int 31, 519–527 (2015). https://doi.org/10.1007/s00383-015-3686-z

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  • DOI: https://doi.org/10.1007/s00383-015-3686-z

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