Challenges faced in management of a neonate with ambiguous genitalia

INTRODUCTION

Neonates with atypical sex development presents as a social and medical challenge for the parents as well as the clinician. It is common in our community where consanguineous marriages are encouraged.¹ Congenital adrenal hyperplasia (CAH) is due to deficiency of enzymes which affect adrenal steroidogenesis. Patients with classic 21OHD and 11OHD have a near complete enzyme deficiency resulting in impaired cortisol synthesis.

CASE REPORT

A 39+6 weeks neonate was born to a 25-year-old G2P1L1 out of non-consanguineous marriage by normal vaginal delivery with birth weight of 2480 grams. Antenatal period was uneventful with no history of exposure to androgens, anti-androgens, progestin, steroids or anti-epileptics. There were no features of visualization in the mother and no family history of malformations, infertility or genetic syndromes. Baby had normal neonatal transition. On examination of the genitalia, baby had hyper-pigmented labio-scrotal fold with unfused labia majora with clitoral size of 10 mm. Prader external masculinization score showed type 3. Ano-genital ratio was 0.6. Testis was not palpable. Vaginal opening was not visualized. Infant’s gender was assigned as indeterminate and was admitted for further management.

A possible diagnosis of female DSD was suspected and evaluated. Anthropometry was within normal values and baby had normal vitals. The baby was subjected to first line investigations. Serum electrolytes and blood sugar values was found to be normal. 17-OHP levels were 733 ng/dl. As a part of second line investigations, Serum ACTH, Testosterone and ACTH was done and was found to be elevated and cortisol was found to be normal. USG abdomen was done which showed normal kidney, urinary bladder and uterus and bilateral adnexa was not visualized. The neonate had no vomiting, poor feeding, lethargy, hypoglycemia or shock. Karyotyping showed 45XX chromosome. Hence a diagnosis of Simple virilizing 46XX CAH (21-Hydroxylase deficiency) was made. Endocrinology opinion was obtained and baby was started on Hydrocortisone 10 mg/m2/day Three times a day and was discharged.

DISCUSSION

The most common DSD presenting in neonatal period is 46 XX DSD with CAH.² More than 95% cases of CAH are due to 21-OH deficiency.³ The challenges faced by a clinician and parent of neonate with atypical sex is briefly discussed.

Challenges in diagnosis

A diagnosis of CAH must be suspected in all neonates with ambiguous genitalia and absent gonads, presumed males with impalpable gonads, masculinized female, neonates with features of adrenal crisis, family history of CAH or unexplained death in infancy. In the absence of newborn screening, the diagnosis of CAH may be missed or delayed.⁴ Simple visualizing type may remain asymptomatic but can have adrenal crisis during severe stress such as sepsis in later life. Prenatal diagnosis and treatment with dexamethasone to prevent virilization of affected female fetuses is another area of controversy.⁴ Delay in diagnosis can result in neonatal mortality in salt wasting forms and incorrect sex of rearing in females with simple virilizing form. Preterm birth and neonatal illness can cause physiological elevation of 17OHP, thus complicating the diagnosis of CAH in the newborn period.⁵

Challenges in gender assignment

Gender identity is influenced by factors such as genetic sex, androgen exposure during neonatal period, appearance of external genitalia, prospects of fertility, choice of gender rearing and religious belief.⁶ In most of DSD, gender must be assigned after discussion with multidisciplinary team. But assigning gender before karyotyping is challenging on a medico legal aspect.

Challenges in initiating and adherence to treatment

Treatment must be started as soon as possible if examination or investigation point towards CAH even before confirmation is awaited. Adherence to treatment and importance of stress dosing should be emphasized to the parents so as to prevent Adrenal crisis and provide near normal life expectancy.⁷ Parents tend to be non-compliant due to adverse effects of treatment such as behavioral issues and poor scholastic performance.

Challenges in follow up

The subsequent management of CAH or other DSD involves long term monitoring of growth and development, hormone therapy, surgical reconstruction procedures, gender assignment, genetic counseling and prognostication which requires multidisciplinary approach and loss to follow up can lead to life threatening events.^7,8

Challenges in counseling parents

The impact of prenatal genetic counseling on parents understanding and psychological preparedness has not been addressed. It is believed that prenatal genetic counseling provides reassurance to parents who remain informed and emotionally ready during gender identification.^7,8 Currently the appropriate time to provide prenatal counseling when ambiguous genitalia is suspected is not available but it is desirable during the third trimester after verifying the parents understanding about the implications of ambiguous genitalia.

Challenges in explaining long term prognosis

Long term prognosis involves post-natal counseling of child with ambiguous genitalia and to educate the parents about recurrence in future pregnancy as a part of prenatal counseling. Parents must be counseled regarding lifelong adherence to treatment and events requiring stress dosing and potential complications encountered during their period of growth and development.

CONCLUSION

Prenatal genetic counseling for parents of fetus with suspected ambiguous genitalia is recommended to reassure the parents and to prepare them psychologically and emotionally and counsel them for prenatal diagnosis and management of subsequent pregnancies. The appropriate time to provide prenatal counseling when fetus with ambiguous genitalia is suspected is still lacking. In view of lack of universal screening in our scenario, a high index of suspicion must be kept and treatment must be started as soon as possible if examination or investigation point towards CAH even before confirmation is awaited. It is necessary to establish stringent follow up protocol by multidisciplinary approach to avoid preventable mortality and morbidity.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

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