Omfalocel, scrot bifid, hipospadias şi micropenis: rezultate clinice în cazuri cu cariotip normal

Introduction

One of the most prevalent congenital abnormali­ties of the anterior abdominal wall is the omphalocele (exomphalos). The midgut and other abdominal organs, including the liver, spleen and gonads, are frequently located within this midline defect, which develops near the umbilical ring⁽¹⁾. The extern amniotic layer, the middle Wharton’s jelly layer, and the intern perito­neal layer form a three-layer covering for the herniated abdominal contents⁽²⁾. The accepted standard of care states routine prenatal screening that should include highlighting the integrity of the anterior abdominal wall and the insertion of the umbilical cord (ISUOG Practice Guidelines updated: performance of the routine mid-trimester fetal ultrasound scan) and the diagnosis of the abdominal wall defect and related anomalies. An early diagnosis enables prenatal counseling and safe delivery at a tertiary care facility with a multidisciplinary team that includes neonatologists, obstetricians and pediatric surgeons⁽³⁾. Over 70% of cases of omphalocele have additional chromosomal abnormality^(4,5). On the long-term survival, related or supplementary anomalies make a significant difference⁽⁶⁾.

Micropenis is a condition that is part of a larger group of issues that are collectively referred to as inconspi­cuous penis. Still, it differs fundamentally from the other diagnostics in this category, such as webbed penis and buried penis, the main issue being the size of the penis itself rather than the skin that covers it. Although iatrogenic causes are rarely found, the hypothalamic-pituitary-gonadal axis is typically the etiology of this illness⁽⁷⁾. The range of prenatal anomalies that can be found before birth includes atypical genitalia development (AGD). These include complex abnormalities for which it is still difficult to determine the sex, such as clitoromegaly, hypospadias and epispadias⁽⁸⁾. There is still no link between prenatal and postnatal observations, and many prenatal diagnoses are incorrect. For example, the lack of distinct boundaries between clitoromegaly and micropenis before birth is a sign of potential confusion⁽⁹⁾.

One of the most prevalent congenital abnormalities in men is hypospadias. Penile curvature, a ventrally lacking hooded foreskin, and proximal displacement of the urethral opening are the usual characteristics of the syndrome. The urethral meatus is situated distally on the penile shaft in roughly 70% of cases; this is regarded as a moderate variant unrelated to other urogenital abnormalities. The other thirty percent are proximal and frequently more complex⁽¹⁰⁾.

In its extreme form of the bifid scrotum, the two scrotal sacs are widely separated, with a fully opened urethra in the form of proximal hypospadias, and the scrotal raphe is not visible. Bifid scrotum is an uncommon congenital defect that affects the midline of the scrotum. Although bifid scrota are typically linked to androgen insensitivity syndrome, hypogonadism and penoscrotal hypospadias, they can also be an isolated genital abnormality linked to maldevelopment and uncommon somatic syndromes⁽¹¹⁾.

For the prenatal and newborn population, intrauterine growth restriction (IUGR) is a significant and sometimes silent cause of severe illness and mortality. It is described as a fetal growth rate that is below average for the particular infant’s growth potential⁽¹²⁾. Obstetricians frequently diagnose intrauterine growth restriction, which entails a higher risk of perinatal mortality and morbidity. The identification of IUGR is essential, because careful assessment and management can lead to a successful outcome⁽¹³⁾.

This article’s goal is to describe omphalocele and micropenis care, along with prenatal diagnosis strategies and postnatal outcomes.

Case presentation

The investigations were conducted in the County Emergency Clinical Hospital of Craiova, a tertiary center. The examination was performed using a Voluson P8 GE HealthCare medical system. A 24-year-old pregnant patient addressed the Prenatal Diagnosis Unit of the Emergency County Hospital of Craiova for second-trimester invasive genetic testing (amniocentesis – screening of chromosomes 13, 18, 21 aneuploidy, X and Y and fetal karyotype by quantitative fluorescent-polymerase chain reaction [QF-PCR]). At 21 weeks of gestation, the fetus was presumed to have an abdominal wall defect (omphalocele) – Figures 1, 2 and 3. Unfortunately, the patient had no first-trimester obstetrical care. The ultrasound evaluation confirmed the omphalocele and, in addition, the fetal sex was declared ambiguous. The ultrasound images revealed a possible bifid scrotum, yet there was an inability for better visualization of the penis (Figure 4). The couple’s current pregnancy was their first, and it is important to note that the pair is Caucasian, non-consanguineous and has no history of sexual strife in the family.

In most pregnancies, sonographic fetal sex determination is possible; nevertheless, in certain instances, it may present challenges. When determining the fetal sex in the late second trimester, sonographic methods rely on the direct view of the external genitalia. If external genitalia cannot be highlighted, the accurate identification of fetal sex may also be aided by other sonographic landmarks, such as the uterus, the descended testis, the fetal scrotum, the midline raphe of the penis, the labial lines, the uterus, and the direction and origin of the fetal micturition jet in males (Figure 5)⁽¹⁴⁾.

The genetics results (screening for chromosome 13, 18 and 21 aneuploidies by QF-PCR from amniotic fluid and classic karyotype) confirmed a normal male fetal karyotype (46 XY) and no duplications or microdeletions of the 13, 18 or 21 chromosomes. Further investigations from the amniotic fluid, such as amniotic fluid testosterone and follicle-stimulating hormone levels⁽¹⁵⁾ and SRY gene⁽¹⁶⁾, were not performed because of the high costs that the family could not afford.

The pregnancy was monitored at the County Emergency Clinical Hospital of Craiova until 36 weeks and 2 days, when an elective caesarean section was performed due to the occurrence of intrauterine growth restriction and chronic fetal distress (Figures 6 and 7).

The postpartum diagnostic was omphalocele, micropenis with a stretched penile length of 1.4 cm, much lower than the average of 4 cm at birth⁽¹⁷⁾ or under 2 cm⁽¹⁸⁾, being able to be easily included in the micropenis spectrum, along with the bifid scrotum and hypospadias (Figure 8).

After six days of care in the newborn service, the patient was transferred to the pediatric surgery clinic, where he underwent omphalocele-reduction surgery (Figure 9). The short-term evolution was favorable, and the patient was discharged after two weeks.

Results

After the patient was discharged, the family continued the hormonal investigations. At the 9-month follow-up, the blood tests revealed a normal thyroid profile, the gonadotropic axis with prepubertal values, prolactin at the upper limit of normal, normal inhibin B, and normal corticotropic axis, but the testicles were not palpable in the scrotum (Figure 10). At 1 year and 2 months, the patient underwent the first hypospadias correction surgery (Figure 11).

Discussion

From what we have investigated so far, the micropenis, hypospadias, bifid scrotum and omphalocele, in our case, represented an isolated anomaly without other associated conditions. However, we know that omphalocele is associated with genetic abnormalities in 70% of cases^(4,5). It is yet unknown, though, whether the presence of micropenis itself has any long-term effects regarding sexual satisfaction and life quality⁽¹⁹⁾. Other studies found isolated micropenis, with no indication of gonadotrophin deficit or a fault in testosterone production, and no indication of a quantitative or qualitative failure in androgen binding. During a crucial stage of development, these isolated abnormalities may result from momentary errors in androgen production, action, or both⁽²⁰⁾. Bhangoo et al. (2010) discovered isolated micropenis with 5-reductase type 2 (SRD5A2) deficiency and AR gene abnormalities, both of which can cause androgen resistance⁽²¹⁾. This study may not be applied to our case, but it is to be considered.

Regarding the omphalocele, studies have found that children with large omphalocele may experience delayed motor development; therefore, the advice was cautious observation and prompt referral to physical therapy for these kids⁽²²⁾. Trisomy 13, 18 or 21 and Beckwith-Wiedemann syndrome are the most prevalent chromosomal anomalies^(23-25). However, in the case of our patient, the karyotype after the amniocentesis came out as normal.

Mulatinho et al. (2012) described a case with severe intellectual disability, omphalocele, hypospadias and high blood pressure. The genetic investigation found an interstitial deletion of 6 Mb in the long arm of the chromosome from 2q22.1 to 2q22.3⁽²⁶⁾. In our case, these anomalies do not seem to be part of a syndrome. Therefore, their association cannot be considered accidental, and microdeletions can be considered. Still, the microdeletions could not be investigated due to the significant costs of these investigations, not provided by the public medical healthcare system, and the lack of other symptoms after birth.

Ludorf et al. (2021) highlighted the fact that, out of 16,442 cases with hypospadias, 12.7% also presented other anomalies such as cardiac, musculoskeletal and additional urogenital defects⁽²⁷⁾.

Other studies presented the association between micropenis-hypospadias and omphalocele, but with the highlighting of several anomalies such as cryptorchidism, presacral dimple, flexion contractures of the fingers, bifid thumb, Simian crease, overriding toes, small for gestational age, hypoglycemia, ocular hypertelorism, microphthalmia, coloboma of the iris, low-set ears, beak nose and micro­gnathia⁽²⁸⁾. Our communication is the first to present this malformative association isolated, and not accompanied by other major structural or genetic abnormalities.

In the specialized literature, the association of micropenis, hypospadias, bifid scrotum and omphalocele, without other anomalies, is quite rare^(29-31), which makes our case different from the rest of the literature.

Conclusions

Structural anomalies can often appear alone, spontaneously, or in association with other structural anomalies as part of syndromes. In our case, micropenis-hypospadias and omphalocele associations were found isolated, despite the detailed prenatal and postnatal evaluation and the literature findings. Fetal growth and well-being should be monitored, as intrauterine fetal growth restriction may occur.

Conflict of interest: none declared  
Financial support: none declared
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