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IAPS Guidelines

Indian Association of Pediatric Surgeons Guidelines on the Management

of Differences in Sex Development

Introduction multidisciplinary committee (LMDC) has a key role in

this individualized decision‑making. If no consensus
T he term DSD – disorders of sexual differentiation
OR differences in sex development – includes
a variety of disorders, some of which manifest as
is reached at LMDC, a state‑level multidisciplinary
committee (SMDC) will act as a nodal center to
“ambiguous genitalia” where the external genitalia guide the LMDC.
is atypical. The new classification proposed is based
on a molecular understanding of sex determination
Local and Apex Multidisciplinary
and development and is sensitive to sociocultural Committee
perspectives[1,2] as these conditions often cause Local multidisciplinary committee
significant emotional and psychological distress to • DSD is to be managed only in centers with an
the affected person and their family if not addressed LMDC
sensitively. • The LMDC would comprise a minimum of three
At the outset itself, it must be understood that DSD specialists
⃰ Pediatrician/pediatric endocrinologist
patients have congenital malformation(s) and these
⃰ Pediatric surgeon
subjects should not be clubbed or confused with
⃰ Child psychiatrist/child psychologist/or a pediatrician
trans‑sexuals or transvestites. Further, the terms such
providing adolescent care.
as hermaphrodites, intersex disorders, and ambiguous
• A medico‑social worker and clinical geneticists may
genitalia have been discarded from the medical use and
also be included, if available.
should not be used.
• All decisions on sex assignment and procedures
Although gender neutral upbringing and a third sex of should be done after thorough evaluation and
rearing are accepted by the legal system in varying discussion with LMDC and the parents/legal
regions, the Indian sociocultural milieu and the parents caretakers
require to have one of the two sexes (male or female) • Minutes of such meetings should be documented and
assigned for every newborn baby to provide a safe and preserved.
socially secure upbringing.[3] Until views and norms of State multidisciplinary committee
our society are radically transformed with education
• SMDC is to be formed at state nodal center (apex
and self‑realization, imposing laws or rules to ban all
institute), and it should comprise the following
medically prescribed surgeries will force the parents
consultants: pediatric surgeon, pediatric
resort to quackery to achieve their aims. Besides, this
endocrinologist, pediatric psychologist/psychiatrist,
is a highly specialized field of pediatric surgical care
geneticist, and medico‑social worker
where few subspecialists or centers manage these
• SMDC would keep a record of all cases sent by
cases optimally, bringing together multiple disciplines
LMDC and act as a nodal center to decide on the
in a cohesive and comprehensive manner. It is vital
that children with DSD continue to receive required
Address for correspondence: Dr. Yogesh Kumar Sarin,
safe, effective medical care from qualified pediatric
Department of Pediatric Surgery, Lady Hardinge Medical College,
surgeons at such select centers. While this document New Delhi ‑ 110 001, India.
aims to serve as a general guideline, the care of E‑mail: yksarin@hotmail.com
each child with DSD must be individualized. A local
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How to cite this article: Sarin YK, Singh D, Babu R, Das K, Rao S; DSD
Guidelines Committee of Indian Association of Pediatric Surgeons. Indian
DOI: 10.4103/0971-9261.352296 Association of Pediatric Surgeons guidelines on the management of
differences in sex development. J Indian Assoc Pediatr Surg 2022;27:376-80.

376
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Sarin, et al.: IAPS guidelines on the management of DSD

management of conditions where a decision is Table 1: DSD Classification[4]

difficult 46XX DSD
• It is recommended to keep a registry of all DSD Androgen excess: CAH, maternal exposure
cases at SMDC. Even cases where decisions have Disorders of ovarian development (gonadal dysgenesis)
been made at LMDC, the minutes must be conveyed 46XY DSD
to SMDC for filing and records Disorders of androgen synthesis ‑ biosynthetic defects,
conversion defects (5 alpha reductase deficiency, 17 beta HSD
• The e‑mail/phone number of contact at SMDC
deficiency)
should be available for all LMDC. AIS states ‑ PAIS or CAIS
Apex multidisciplinary committee Disorders of testicular development (gonadal dysgenesis)
• Apex multidisciplinary committee (AMDC) would be Sex chromosome DSD
a national‑level committee constituted by the Indian 45XO/46XY (mixed gonadal dysgenesis)
46XX/46XY (ovotesticular DSD)
Association of Pediatric Surgeons whose members
*Cases of CAIS, PMDS, vaginal atresia, cloacal exstrophy, turner/
could be referred difficult cases by different SMDCs.
Klinefelter syndromes, and proximal hypospadias with bilateral
This committee shall engage with the relevant palpable undescended testis may cause atypical genitalia in the
ministries of Central Government and suggest newborn and will need specific evaluation. PMDS: Persistent
reforms and policy matters for the DSD patients. Mullerian duct syndrome, CAH: Congenital adrenal hyperplasia,
AIS: Androgen insensitivity, PAIS: Partial AIS, CAIS: Complete
Differences in Sex Development AIS, DSD: Differences in sex development, HSD: Hydroxy‑steroid
Classification deficiency

Clinical Assessment and Evaluation • In centers where these facilities are not available,
the neonate should be appropriately referred after
A basic initial clinical evaluation should include stabilization
and documents the following details • In an infant with a combination of any of these:
• Appearance of genitalia – whether atypical [Table 1][4] Karyotype of 46XX, significantly elevated
• Location of urethral meatus serum 17OHP, typical electrolyte disturbances,
• Phallic structure: Size (stretched flaccid phallic and the presence of uterus: Congenital adrenal
length, corporal body girth) hyperplasia (CAH) due to 21‑hydroxylase deficiency
• Gonads: Location (bilateral nonpalpable/unilateral must be identified and managed expeditiously
palpable or nonpalpable), consistency (firm/soft, • The identification and management of the other
homogeneous/heterogeneous) DSDs outlined below are comparatively less
• Genital folds: Labial/scrotal/labioscrotal; fusion of emergent.
labioscrotal folds, anogenital ratio, and anogenital Further evaluation
distance (posterior labial fusion) • Human Chorionic Gonadotrophin (hCG) stimulation
• Presence of separate vaginal and urethral opening or test: When the karyotype is 46XY, a standard hCG
single urogenital sinus stimulation is useful in differentiating the subtypes
• Abdominal examination. of XY DSD (testosterone [TST] biosynthetic
defects, conversion defects, and AIS)
Standardized scores such as Prader Scale and External • In gonadal dysgenesis/disorders of androgen
Masculinization Score should be used. synthesis – Elevated gonadotropins luteinizing
First tier of investigations in infants with atypical hormone/ follicle stimulating hormone (LH/FSH),
genitalia and/or bilateral impalpable gonads no increase in TST or dihydrotestosterone (DHT)
includes the following • In AIS – Proportional increase in TST and DHT
with low gonadotropins
• A screening ultrasonography to evaluate the
• In 5 alpha reductase deficiency (ARD) – Increase in
presence of the uterus, gonads, and obstructive
TST but not DHT, elevated TST/ DHT ratio, low
features (hydrometrocolpos, hydronephrosis, etc.)
gonadotropins
that might endanger life • To identify gonadal details and Mullerian structural
• Serum 17OH‑progesterone (17OHP) and serum derivatives
electrolytes • Noninvasive imaging: Ultrasonogram/magnetic
• The results of polymerase chain reaction or resonance imaging scan
fluorescence in situ hybridization analysis using • Genitogram
Y‑ and X‑specific markers should be obtained as • Examination under anesthesia and requisite
soon as possible. Conventional karyotyping is always endoscopy (genitoscopy and laparoscopy), gonadal
performed to confirm the chromosomes. biopsy.

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Sarin, et al.: IAPS guidelines on the management of DSD

Standard, international diagnostic algorithms and Sex assignment process in the neonatal period
nomograms are followed to complete the rational and Sex assignment process may be “noncontroversial” in
scientific diagnostic process. conditions such as
Guidelines for newborn • CAH – 46XX: There is a worldwide consensus
on female sex of rearing; however, the timing of
• Any sick newborn with ambiguous genitalia should
reconstructive surgery is still evolving
be investigated on an emergency basis considering
• Severe hypospadias with bilateral palpable
the life‑threatening steroid crisis in CAH – the
testis – 46XY; there is worldwide consensus on male
common form of DSD. Unexplained electrolyte
sex of rearing. The optimal age for correction is
imbalance with a history of loss of sibling in similar
9–18 months.
circumstances is strongly suggestive of CAH
• Whenever DSD is suspected, baseline investigations Sex assignment can be “difficult” in the following
in consultation with pediatrician/endocrinologist are conditions
to be done, followed by a meeting arranged between • Mixed genetic composition (XO/XX; XO/XY,
the family and the team of experts as suggested XX/XY); or where there is disparity between
for the LMDC. The aim of such a comprehensive genetic/composition and internal genital/gonadal
meeting is to convey details about the suspected anatomy (ovotesticular DSD, gonadal dysgenesis)
disorder and discuss the further line of management • In some XY DSD (conversion defects, PAIS) and
with the caretakers. This allays their fears and reduces pure/mixed gonadal dysgenesis (MGD) – It can be
the stress. The fact that the baby has a potential to be confusing. In these, the LMDC can decide on the
a functional member of the society is emphasized. sex of rearing after all information is available.
When further clarification is needed, SMDC can be
Parental Counseling and Gender consulted.
Assignment General Principles of Gender
General principles
Assignment in the Newborn
• Assigning a sex of rearing is a great responsibility
• CAH (XX karyotype; elevated 17OHP): Female
and must be systematic
sex is favored as they have normal female internal
• The first conversations with the family need to set
genitalia and fertility potential
a positive tone. When addressing the infant, it is
• CAIS and pure forms of gonadal dysgenesis are
important to initially be gender neutral. Use “it/baby”
raised as females with requirement for minimal
instead of “he/she” that could inadvertently bias the
surgical interventions in the future
family toward a gender • 46 XY conversion defects (5 ARD, 17 beta
• Sex assignment decisions should be based upon hydroxy‑steroid deficiency [HSD] deficiency): These
information accrued from clinical examination, children usually virilize at puberty (phallic length
investigations, and multidisciplinary meetings. It increases; testicles descend). Hence, a male sex of
takes into account the age at presentation; fertility rearing is favored
potential; size of the phallus and sexuality issues; • 46XYY, PAIS: Sex of rearing may be determined by
projected risk of pubertal virilization and associated the phallic size and response to hCG during testing.
gender dysphoria;[5] and parental/legal caretaker The latter predicts the pubertal phallic growth with
opinion/wishes TST supplementation. Frequently, due to the small
• When an older child presents where the family has size of phallus, these children are reared up as girls.
already reared as a male/female, any decision for sex However, in those with androgen effects, male sex of
reassignment is made after extensive consultation rearing is possible
with the child, the parents/caretakers about the • MGD (46, X/46, XY): Variable sex of rearing
scientific basis, future projections of medical issues, depending on proportion of dysgenic/functional internal
and pros/cons of reassigning the sex gonad and external anatomy. Often, due to androgen
• SMDC must be involved in situations where sex effects (due to one functioning testis), virilization is
reassignment is sought manifested that may favor a male sex of rearing
• If the child is >12 years, it is essential to involve • Ovotesticular DSD variable sex of rearing depends
the child in all decisions, and a verbal/written assent on internal and external anatomy. The fertility
may be used for any procedures. potential is better if reared as female.

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Sarin, et al.: IAPS guidelines on the management of DSD

Timing and Nature of Surgical • CAH reared as boys or with overt masculine
Interventions in Differences in Sex orientation/gender dysphoria: In this rare situation,
SMDC may be consulted if a sex re‑assignment is
Development requested. If male sex identity is established, these
There is considerable debate as to the optimal timing of children will need hysterectomy/gonadectomy that
any genital surgery. Decisions about nature and timing of may be delayed until puberty when informed assent
any surgery are made after discussions with the family of the adolescent is obtained.
and in the LMDC. At all stages, the following factors are
considered – family concerns, psychological impact on the Risk of Germ Cell Malignancy
child, technical ease of reconstructive surgery, anesthetic • Low risk: Turner syndrome (‒Y) ‒1%, CAIS – 2%;
issues of multiple‑staged reconstructive surgery.[6] ovotesticular DSD – 3%[7]
Circumstances in which genital surgery is • Intermediate risk: Turner syndrome (with Y) – 12%;
permissible 17 beta HSD ‒ 28%; gonadal dysgenesis (scrotal
When a potentially “life‑threatening” circumstances gonad) – not known; PAIS (scrotal gonad) – not
arise (e.g., sepsis/obstructive uropathy, risk of gonadal known
malignancy) on the child with DSD, the interest of the • Highest risk: Gonadal dysgenesis (with
child is of paramount importance and a quick decision Y) – intra‑abdominal gonad – 15%–35%;
can be made, preferably in communication with the Denys‑Drash (with Y) – 40%, PAIS (nonscrotal
LMDC. gonad) – 50%; MGD–Frasier syndrome – 60%.
• DSD with retained menstrual or mucinous fluid or
recurrent urine infection/urosepsis due to obstruction
Gender Dysphoria/Gender Identity
to outflow due to common urogenital channel Disorder
requires urgency diversion procedures (minimally • Gender dysphoria is low in women with CAH (<5%),
invasive/surgical), e.g., percutaneous nephrostomy, CAIS (<2%), and PGD (<5%)[5]
vaginostomy • Gender dysphoria is variable (25%–40%) in PAIS,
• In children with certain forms of DSD (mixed gonadal MGD, ovotesticular DSD
dysgenesis with streak gonads, PAIS), the risk of • Gender dysphoria is high in women with 5 ARD/17
cancer is high making it potentially “life‑threatening.” beta HSD (>50%).
Excision biopsy of streak/dysgenetic gonad. In PAIS/
CAIS, gonads are kept until adolescence as malignant Psychological Assessment, Gender
risk is minimal till such time and it aids spontaneous Orientation Assessment, and Age of
pubertal development Consent
• Once sex of rearing has been conclusively decided, • Gender orientation instruments are available in all
the incongruent gonadal tissue or genital duct (e.g., age groups
testicular tissue and vas deferens in ovotesticular • Child psychologist or psychiatrist who is experienced
DSD raised as females) can be removed with due in this field must be involved whenever indicated to
informed consent. aid in decision‑making
Circumstances in which genital surgery is • A child <12 years of age is not eligible for legal
controversial consent in Indian Law
Congenital adrenal hyperplasia • However, children aged 7–12 years can provide
• Often, proper steroid suppression suffices to control mild verbal assent and 12–18 years can provide written
clitoromegaly in CAH. However, if severe refractory assent which can be obtained along with parental
clitoromegaly and painful erection are an issue, LDMC/ consent.
SMDC should consulted before the intervention Financial support and sponsorship
• There has been a move away from early vaginoplasty Nil.
in childhood, and one may wait till puberty when
Conflicts of interest
a single‑stage urovaginal reconstruction can be
undertaken with informed consent of the adolescent. There are no conflicts of interest.
However, in cases where there are urinary infections Yogesh Kumar Sarin, Dasmit Singh1, Ramesh Babu1,
or when there is obstruction to urogenital tract, Kanishka Das1, Sanjay Rao1, DSD Guidelines Committee
early surgery may be required. The LMDC must be of Indian Association of Pediatric Surgeons
informed and early permission sought. Department of Pediatric Surgery, Lady Hardinge Medical

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Sarin, et al.: IAPS guidelines on the management of DSD

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of sex development and their families [individualized care for
Submitted: 06-Jun-2022 patients with intersex (Disorders/differences of sex development):
Revised: 05-Jul-2022 Part 2]. Pediatr Urol 2020;16:606‑11.
Accepted: 05-Jul-2022
4. Cools M, Nordenström A, Robeva R, Hall J, Westerveld P,
Published: 26-Jul-2022
Flück C, et al. Caring for individuals with a difference of sex
References development (DSD): A consensus statement. Nat Rev Endocrinol
2018;14:415‑29.
1. Lee PA, Houk CP, Ahmed SF, Hughes IA; International 5. Babu R, Shah U. Gender identity disorder (GID) in adolescents
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Wilkins Pediatric Endocrine Society and the European A systematic review and meta‑analysis. Pediatr Urol
Society for Paediatric Endocrinology. Consensus statement on 2021;17:39‑47.
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Conference on Intersex. Pediatrics 2006;118:e488‑500. Baker L, Baskin LS, et al. Surgery in disorders of sex
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