Application of management algorithm to a series of patients of disorders of sexual differentiation from Southern India: A case series

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A neonate presenting with ambiguous genitalia is a social emergency as decision-making related to gender assignment is difficult for family and health professionals 4 .Clinical diagnosis, surgical/ medical treatment options, and need for hormone therapy have to be considered along with wishes of family and prevailing cultural practices.These may have long-term effects on gender identity, fertility and tumorigenesis affecting quality of life in later years 5 .Thus, management of DSD requires a coordinated approach by a team comprising paediatrician, endocrinologist, paediatric surgeon, a radiologist together with a skilled laboratory set-up 6 .Figure 1 is a diagnostic algorithm for DSD.

Case series
There were 7 cases of ambiguous genitalia presenting to our centre from January 2019 to June 2020.Diagnosis was based on published criteria for diagnosing DSD 2,4,5 .Each patient's data, clinical features and laboratory findings were analysed by the specialist team as per algorithm shown in Figure 1.A detailed history was taken and physical examination was done and recorded after taking consent from parents/guardians of these patients.
Chromosomal gender was assigned based on the karyotype.An ultrasonogram (USG) was done to identify gonads, Wolffian duct remnants, Mullerian remnants and other malformations.Hormonal and biochemical tests as mentioned in table 3 were performed based on the individual clinical profile.Magnetic Resonance Imaging (MRI) of the pelvis was done in one case to identify remnants of Mullerian duct as these were not visualized in the USG of the pelvis.
The clinical characteristics of the 7 patients are shown in Table 1.The ages ranged from 7 days of life to 5 years of age; 6 (85%) were products of a consanguineous marriage;

Discussion
DSDs are a diverse group of disorders.The disorders mentioned in our case series are very rare like aromatase deficiency (only a few cases reported worldwide) 7 , 46XX ovo-testicular DSD (1 per 20,000) 8 , androgen insensitivity syndrome (2 to 5 per 100,000) 9 and 5 alpha reductase deficiency (incidence unknown) 9 .
Features suggestive of DSD include cases with overt genital ambiguity, apparent male genitalia with bilateral cryptorchidism, hypospadias with unilateral cryptorchidism, severe cases of hypospadias like penoscrotal, perineal or scrotal, apparent female genitalia with enlarged phallus or inguinal hernia or palpable testes and cases with anatomical or karyotypic discordance 6 .
A thorough clinical history and detailed clinical examination is the cornerstone of diagnosing DSD.Details should be taken about consanguinity and family history of similar disorders in other members.Clinical examination traditionally starts with the presence or absence of palpable gonads along with measurement of length of phallus, and noting the presence of hyperpigmentation and dysmorphism.This should be followed by initial investigations like fluorescence in situ hybridization (FISH) /polymerase chain reaction (PCR) for early detection of XY chromosomes followed by complete karyotype to look for mosaicism.It should also include assessment of internal organs by USG and if required MRI should be done to look for intra-abdominal organs.Further evaluation should be directed as given in the simplified algorithm (Figure 1) Genetic testing like microarray is used to look for deletions in infants with syndromic DSD 5 .Newer techniques like whole exome sequencing and next generation sequencing help in specific diagnoses of previously undiagnosable cases.

Conclusions
There were 2 cases of 46, XX ovo-testicular DSD and 1 case each of aromatase deficiency, congenital adrenal hyperplasia, 5 alpha reductase deficiency, testicular dysgenesis and androgen insensitivity syndrome.

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Dept. of Paediatrics, Military Hospital Mathura, India, 2 Dept. of Paediatrics, Military Hospital Hissar, India, 3 Dept. of Paediatrics, Military Hospital Jaipur, India, 4 Dept. of Paediatrics, Military Hospital Sagour, India, 5 Dept, of Paediatrics, Military Hospital Ahmedabad, India *Correspondence: drsudhanshuafmc@gmail.comhttps://orcid.org/0000-0002-7227-9747(Received on 25 May 2023: Accepted after revision on 21 July 2023) The authors declare that there are no conflicts of interest Personal funding was used for the project.Open Access Article published under the Creative Commons Attribution CC-BY License