Background: Advanced paternal age associated comorbidities and reduced fertility possess significant risks of genetic disorders to the offspring. With a broad implementation of a non-invasive prenatal testing (NIPT) and invasive assessment leads to more cases of genetic disorders, including sex discordance are revealed. Among biological causes of sex discordance are disorders of sexual development. The main aim of present case study is prenatal diagnosis of sex differentiation disorders with focus on the role of ultrasound scans for assessment of prenatal diagnosis.

Case Presentation: In this report 37-year-old pregnant woman with 22-23 weeks gestation refer to center expert opinion regarding perineal abnormalities. On sonography at our centre we notice positive findings are as: micropenis with bifid scrotum or it could be ambiguous genitalies, which falls in group of disorders of sexual differentiation. As Karyotyping was primarily assess by local doctors by amniocentesis which was XY.

Conclusion: Genotype-phenotype correlation might improve prenatal diagnosis of Fetuses who are having DSD (disorder of sex differentiation). Combining ultrasonic examination with genetic analysis will definitely improve accurate prenatal diagnosis.

• Hypospadias

• DSD (disorder of sex differentiation)

• Antenatal diagnosis

• Ultrasound scan

Patel BI, Chauhan J, Patel N, Patel S (2024) Prenatal Difficult Diagnosis of Perineal Abnormalities by 2d-3d Usg; Turns Out to Be Severe Hypospediasis with Bifidscrotum - A Case Report. Med J Obstet Gynecol 12(1): 1182.

Hypospadias is a developmental anomaly in which the urethra opens on the ventral side of the penis. It is the most common congenital defect of the genitalia and is often missed on prenatal ultrasound examination [1]. It is a cause of concern and psychological trauma for the child and the parents [2]. Most prenatally diagnosed cases have been attributed to distal hypospadias with ultrasound findings of anomalous distal morphology of the penis, small lateral folds, small penis with ventral incurvation or the presence of an anomalous urinary stream [3]. We report the prenatal diagnosis of sever form of hypospadias in which penile size was short with bifid scrotum with uretral opening at penoscrotal region.

We report a case of disorders of sexual development of foetus. At our tertiary care centre, a 37-year-old (gravida 2, para 1 live 1 male child normal development) woman with 22- 23wks pregnancy was referred to us for assessment of perineum. While assessing the perineum on 2D an unusual perineum was observed, so we did 3D assessment of perineum. As previous doctor has genetically confirmed that intrauterine foetus is XY but there was a disparity in perineal USG findings.

Big glans tubercle or phallus with bifid scrotum was notice on 3D sonography (Figure 1 to 8).

Figure 1: 3D USG with presence of bifid scotum and small phallus

Figure 2: 3D USG with presence of bifid scrotum and small blunt phallus

Figure 3: Transperineal scan with the 4D/3D probe held in a transverse position related to the perineum.

Figure 4: 3D USG at transverse perineum, bifide scrotum with small phallus

Figure 5: 3D USG bifid scrotum with phallus in obliqe sagital view

Figure 6: 3D USG, phallus with scrotum

Figure 7: 3D multiplanner USG, small phallus with bifid scrotum, there is cleft seen in between scrotum.

Figure 8: 3D USG we can see the position of small phallus and bifid scrotum

A rounded smooth bulbous tip of phallus shaft was notice rather than the normal pointed morphology. Length of penile shaft was very short. Two parallel echogenic lines seen on either side of tip of the phallus which can be seen on 2D sonography (Figure 9,10).

Figure 9: 2D USG at transperineum, echogenic line seen both side of phallus.

Figure 10: 2D USG at transperineum, echogenic line seen both side of phallus. 3 hand arrow - ecogenic line, phallus, echogenic line Genetic assessment was XY.

On the completion of the sonography we were in dilemma of either clitoromegaly, hypospadias or it could be ambiguous genitalies but its genetic report of XY (Figure 11 and 12),

Figure 11: Result of karyotype obtained by amniocentesis

Figure 12: Result of karyotype obtained by amniocentesis

which was with patient, compelled us to take antenatal opinion of paediatric urologist. Paediatric urologist guided us regarding DSD, postnatal management & prognosis of child, however patient was not ready for postnatal management & its outcome regarding DSD. Patient opted for termination and post termination we correlate the finding of sonography with post aortal specimen.

While assessing abortus specimen, urinary stream comes from bifid scrotal apex as one can notice on figure sonography (Figure 13 and 14).

Figure 13: Small globular short penis with bifid scrotum in aborted fetus

Figure 14: Urinary stream seen from cleft between scrotm when gentle pressure applied at perineum in aborted fetus.

Human sexual differentiation is a highly complex process under the control of multiple genes and hormones [4-6], if at birth doctor is not able to declare the sex of the new-born, it will be a social emergency. DSD is common occurrence & approximately 1 per 4500 live births. We should always keep in mind regarding congenital adrenal hyperplasia (CAH) which is the most common diagnosis in 46XX cases presenting with ambiguous genitalia. Those with 46XY have a wider range of diagnosis. With advances in ultrasound industries, perineal abnormalities can be picked up as early as 15 weeks of gestation [7,8]. The suspicion of ambiguity of the genitalia can arise under several circumstances, including a reduction in penile size for gestational age or an absent phallus, curvature of the phallus, scrotal phallic malposition or fusion, apparent fusion of the labia or indeterminate sex. The other stimulus to the diagnosis is when discordance is observed between the sonography fetal sex & fetal karyotype. It is not always possible to differentiate between clitoromegaly and micropenis unless there is normal development of the scrotum with evidence of testicular descent which will be late GA. As determining the fetal male gender is based on the identification of a penis and scrotum, it did not take long to focus attention on testicular descent. In 1983 Birnholz 8 reported that the testes do not descend into the scrotum before 26 weeks of gestation. In that study, 62% of foetuses had descent at 28-32 weeks and 95 % after 32 weeks. Fifteen years later these results were confirmed by Achiron et al. [9], who also developed a nomogram for scrotal circumference, showing that scrotal size increases with gestational ageto assist in assessing the development of the fetal penis, reference ranges for penile length were constructed [10,11], the penile length increases from 3.9 mm at 14 weeks of gestation to 23.8 mm at 38 weeks. Fetal USG can be used to accurately predict gender from around 12 week of gestation. Fetal sex assignment in the first trimester can be useful in pregnancies at risk of severe sex-linked diseases, in disorders involving ambiguous development of the genitalia, and in determining zygosity in multiple foetuses. Prenatal diagnosis of ambiguous genitalia can assist in the diagnosis of many malformation syndromes, and in other cases alert the health professional and parents to the possibility of underlying hormonal abnormalities that may require urgent intervention in the new-born period [12].

In conclusion, as ambiguous genitalia can be life threatening issue especially in enzyme defects according to the deficient enzyme type, external genitalia evaluation should be a part of routine anomaly screening. Hypospadias is an abnormality of anterior urethral and penile development in which the urethral opening is located on the ventral side of penis instead of the tip [13-15]. The incidence is estimated between 0.2 and 4.1 per 1000 live births [19], and it seems to increase with increasing maternal age [16,17]. The recurrence risk of having a second male child with hypospadias is between 4 and 12 % [17,18]. The cause of hypospadias s uncertain. It has been suggested that it is not just a local dysmorphic phenomenon but may be a local manifestation of systemic endocrinopathy, representing a defect in the ability of the target organ to respond to androgens, because of either a reduced number of androgen receptors or a partial inability to convert testosterone to dihydrotestosterone [20]. The most common associated anomalies are other urogenital anomalies (40%) such as vesicoureteral reflux (VUR), ureteropelvic junction obstruction (UPJO) and cryptorchidism (8–10%) [21]. 

Severe form of hypospadias was diagnosed prenatally following sonographic detection [22]:

1. A blunter bulbous tip to the penile shaft rather than the normal pointed morphology.

2. Various degrees of abnormal curvature of the penis.

3. A short penile shaft.

4. Observation of the two parallel echogenic lines corresponding to the dermal remains of the prepuce.

5. Ventral deflection of the urinary stream which can be studied also by color Doppler.

6. “Tulip sign”: small blunted-ended penis between two scrotal folds.

7. In our experience, a “tulip sign” may not be so obvious at early second trimester. A pointed tip of the penis can still be noted during erection even if the fetus is a victim of severe hypospadias, and this finding should not be mistaken as normal male external genitalia.

Genotype-phenotype correlation might improve prenatal diagnosis of Fetuses who are having DSD (disorder of sex differentiation). Combining ultrasonic examination with genetic analysis will definitely improve accurate prenatal diagnosis.

Ethics Approval

The study protocol was reviewed and approved by the Institutional Ethics Committee. The study was carried out following the standards of clinical study as laid down in Schedule Y and new drugs and clinical trial act, 2020.

Consent to Participate

The participant was explained clearly about the nature and purpose of the study in the language they understood and written informed consent was obtained from him. The participant was ensured that their identity will not be revealed at any stage of the study.

Consent to Publish

The  authors  affirm  that  human  research  participants provided informed consent for publication of the all the images.

Author’s Contribution

Dr. BP has designed the concept of the study. Dr. JC has done literature review and data collection and analysis. Dr. NP has contribution in treatment of patients and manuscript writing. Dr. SP has reviewed the manuscript draft and done all necessary corrections.
Availability of Data and Materials: The datasets used and/ or analysed during the current study are available from the corresponding author on reasonable request.

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