Ambiguous genitalia in neonates

Last reviewed: September 2018

Last updated: December 2017

Summary

Ambiguous genitalia (i.e., a genital phenotype that is neither clearly male nor female) are caused by the atypical development of chromosomal, gonadal, or anatomical sex. The complex group of disorders that cause ambiguous genitalia are called disorders of sex development (DSD).

DSD are congenital conditions that most commonly present in the newborn period.

DSD can be classified as sex chromosome DSD, 46,XY DSD, or 46,XX DSD .

Sex chromosome DSD results from the atypical complement of sex chromosomes, and includes syndromes such as Turner syndrome (45,X with one absent sex chromosome) and Klinefelter syndrome (XXY with one additional X chromosome). Mosaicism occurs when more than one type of chromosomal arrangement is present (e.g., 45,X/46, XY).

46,XX DSD are conditions characterised by excess exposure to androgens. Over 95% of causes of ambiguous genitalia with a 46,XX genotype are due to congenital adrenal hyperplasia secondary to 21 hydroxylase deficiency.

46,XY DSD can be due to several aetiologies and usually requires a more extensive diagnostic evaluation.

The initial management of a neonate with ambiguous genitalia is a social and clinical emergency. The local team has a key role in coordinating the initial assessment and investigations, and supporting parents. It is important there is early discussion with a more specialist multidisciplinary team with expertise in paediatric endocrinology, genetics, and surgery, and with appropriate psychiatric/psychological support. For many DSDs, long-term surgical and psychosexual outcomes remain uncertain.

Definition

Disorders of sex development (DSD) are congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. [1] A subset of children with DSD present at birth with ambiguous genitalia (i.e., a genital phenotype that is neither clearly male nor clearly female) and without other dysmorphic features. Many causes have a genetic basis. A very rare exception may occur when there is virilisation of a 46,XX fetus by maternal virilising tumours or maternal exposure to androgenic drugs.

This topic addresses the initial approach to neonates with ambiguous genitalia who are not identified as having a specific chromosomal syndrome in which ambiguous genitalia may be one of a number of presenting features.

History and exam

Key diagnostic factors

ambiguous genitalia with no palpable gonads
ambiguous genitalia with one palpable gonad
ambiguous genitalia with bilaterally palpable gonads
penile length <2.5 cm in a phenotypic male
clitoris >1 cm in a phenotypic female
hypospadias and undescended testes or separation of scrotal sacs
urethral opening at base of phallus

Full details

Other diagnostic factors

hypotension and vomiting
dysmorphic facial features

Full details

Risk factors

family history

Full details

Diagnostic investigations

1st investigations to order

chromosome analysis (karyotype)
serum electrolytes and glucose
pelvic ultrasound

Full details

Investigations to consider

serum 17 hydroxyprogesterone
plasma renin activity
serum 11 deoxycortisol and 11 deoxycorticosterone
serum testosterone
serum dihydrotestosterone
serum LH and follicle-stimulating hormone (FSH)
adrenocorticotropic hormone (ACTH) stimulation test
human chorionic gonadotrophin (hCG) stimulation test
Müllerian-inhibiting substance (MIS) or anti-Müllerian hormone (AMH)
urine steroid profile

Full details

Treatment algorithm

INITIAL

Contributors

Authors VIEW ALL 

Justin H Davies, MD, FRCPCH, MRCP

Consultant Paediatric Endocrinologist

Honorary Senior Lecturer

University of Southampton

Southampton

Disclosures

JD declares that he has no competing interests.

Gemma Watts, BMS, MRCPCH

Specialist Registrar in Paediatric Endocrinology

Department of Paediatrics

University Hospitals Southampton NHS Trust

Southampton

Disclosures

GW declares that she has no competing interests.

Acknowledgements

Dr Justin Davies and Dr Gemma Watts would like to gratefully acknowledge Dr Ingrid A. Holm, a previous contributor to this monograph. IAH declares that she has no competing interests.

Peer reviewers VIEW ALL 

Paul Saenger, MD, MACE

Professor of Pediatrics

Department of Pediatrics (Endocrinology)

Montefiore Medical Center

Albert Einstein College of Medicine

New York

Disclosures

PS declares that he has no competing interests.

Mary M. Lee, MD

Professor of Pediatrics and Cell Biology

Vice-Chair of Academic Affairs in Pediatrics

Pediatric Endocrine Division

UMass Medical School

Worcester

Disclosures

MML declares that she has no competing interests.

Patricia Y. Fechner, MD

Associate Professor Pediatrics

Pediatric Endocrinology

University of WA

Medical Director of DSD Program

Seattle Children’s Hospital

Seattle

Disclosures

PYF declares that she has no competing interests.

Use of this content is subject to our disclaimer

Ambiguous genitalia in neonates

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

all neonates presenting with ambiguous genitalia

46,XX: congenital adrenal hyperplasia secondary to 21 hydroxylase deficiency (at presentation)

46,XY

46,XX: congenital adrenal hyperplasia secondary to 21 hydroxylase deficiency (following sex assignment)

46,XY

45,X/46,XY mixed gonadal dysgenesis

Contributors

Authors VIEW ALL 

Justin H Davies, MD, FRCPCH, MRCP

Disclosures

Gemma Watts, BMS, MRCPCH

Disclosures

Acknowledgements

Peer reviewers VIEW ALL 

Paul Saenger, MD, MACE

Disclosures

Mary M. Lee, MD

Disclosures

Patricia Y. Fechner, MD

Disclosures

Differentials

Guidelines

View PDF