Disorders of Sexual Development — MCQs

10 questions

Which of the following is the least common cause of ambiguous genitalia in a female child

A GSP4 woman comes for routine sonography for the first time. She has four daughters and expresses a desire for a boy this time, asking for sex determination. To abide by ethical guidelines, what should you do?

What should be done next in an 18-year-old girl with primary amenorrhea, a karyotype of 45,X0, and an infantile uterus on ultrasound?

Which of the following conditions is least likely to present with ambiguous genitalia?

Congenital adrenal hyperplasia most commonly presents as

A 10 day old male pseudohermaphrodite child with 46 XY karyotype presents with BP of 110/80 mmHg. Most likely enzyme deficiency is:

A teenage girl presents with a history of amenorrhea. Local examination is shown in the image. What karyotype analysis would you consider for further evaluation?

A 16-year-old girl comes to you with primary amenorrhea; on evaluation there is absent breast development, she has a normal stature, her FSH and LH levels are found to be high and she has a karyotype of 46XX. What is the probable diagnosis?

An eight-year-old girl presented by her mother with sexual precocity. She may have the following disorder:

Q10

In Precocious puberty, the age limit for girls is?

Disorders of Sexual Development Indian Medical PG Practice Questions and MCQs

Question 1: Which of the following is the least common cause of ambiguous genitalia in a female child

A. WNT-4 gene mutation
B. Congenital adrenal hyperplasia
C. Fetal placental aromatase deficiency (Correct Answer)
D. Fetal placental steroid sulfatase deficiency
E. Maternal androgen exposure

Explanation: ***Fetal placental aromatase deficiency*** - This condition is exceedingly rare and is considered one of the **least common genetic causes** of ambiguous genitalia in a female. - Deficiency of **aromatase** in the placenta prevents the conversion of androgens to estrogens, leading to **masculinization of a female fetus**, but this pathway is only a minor contributor to fetal androgenization. *WNT-4 gene mutation* - **WNT-4** is crucial for **female sexual differentiation** and acts as an anti-testis factor. - Mutations can lead to **Müllerian aplasia** and variable degrees of virilization in genetic females, making it a recognized, though not the most common, cause of ambiguous genitalia. *Congenital adrenal hyperplasia* - This is the **most common cause** of ambiguous genitalia in a female, primarily due to **21-hydroxylase deficiency**. - Excess adrenal androgens lead to **virilization** of the external genitalia in genetic females. *Maternal androgen exposure* - Virilization can occur from **maternal sources** such as androgen-secreting tumors, exogenous androgen use, or aromatase inhibitors during pregnancy. - This is an **uncommon but recognized cause**, more frequent than aromatase deficiency but far less common than CAH. *Fetal placental steroid sulfatase deficiency* - This deficiency typically results in **low maternal estrogen levels** and can cause **placental insufficiency** and abnormalities in labor, but it does **not directly cause ambiguous genitalia** in a female fetus. - While it affects steroid metabolism, it does not lead to the accumulation of androgens necessary for virilization of female external genitalia.

Question 2: A GSP4 woman comes for routine sonography for the first time. She has four daughters and expresses a desire for a boy this time, asking for sex determination. To abide by ethical guidelines, what should you do?

A. Check routine ANC and sex for developmental abnormalities and do not reveal gender to the patient (Correct Answer)
B. Check routine ANC and sex for developmental abnormalities and do reveal gender to the patient
C. Do reveal gender if a girl
D. Check only routine ANC, do not check sex

Explanation: ***Check routine ANC and sex for developmental abnormalities and do not reveal gender to the patient*** - It is **illegal** and **unethical** to reveal the sex of the fetus in many countries, including India, to prevent **sex-selective abortions**. - The primary purpose of a routine antenatal ultrasound is to assess fetal **health** and **developmental abnormalities**, not to determine sex for parental preference. *Check routine ANC and sex for developmental abnormalities and do reveal gender to the patient* - Revealing the gender to the patient directly facilitates **sex-selective abortion**, which is medically unethical and illegal due to the potential for harm to the fetus and society. - This practice would violate the **Pre-Conception and Pre-Natal Diagnostic Techniques (PCPNDT) Act** in India, which prohibits gender determination. *Do reveal gender if a girl* - Revealing the gender, regardless of whether it is a boy or a girl, can lead to **gender-biased selective abortions**, particularly in cultures with a strong preference for male offspring. - This action undermines the ethical principles of **non-maleficence** and **justice** by potentially facilitating harm based on gender preference. *Check only routine ANC, do not check sex* - While the primary focus is routine antenatal care, avoiding the assessment of fetal sex entirely could lead to **missing potential developmental abnormalities** that might be identifiable through observation of external genitalia. - A thorough ultrasound examination routinely includes a visual check of fetal anatomy, which can incidentally reveal gender, but this information should not be shared with the parents for selection purposes.

Question 3: What should be done next in an 18-year-old girl with primary amenorrhea, a karyotype of 45,X0, and an infantile uterus on ultrasound?

A. Vaginoplasty
B. Clitoroplasty
C. B/L gonadectomy
D. Hormone therapy to induce puberty (Correct Answer)

Explanation: ***Hormone therapy to induce puberty*** - The patient has **Turner syndrome (45,X0)**, which causes **gonadal dysgenesis** and thus a lack of **estrogen** and **progesterone** production, leading to primary amenorrhea and an infantile uterus. - **Hormone replacement therapy** with estrogen and progestin is essential to induce secondary sexual characteristics, promote uterine development, and achieve cyclical bleeding, which mimics puberty. *Vaginoplasty* - **Vaginoplasty** is a surgical procedure to create or lengthen the vagina, typically considered for conditions like **Mayer-Rokitansky-Küster-Hauser syndrome** where the vagina is absent or underdeveloped but ovaries are functional. - This patient has an infantile uterus, not vaginal agenesis as the primary issue, and the underlying problem is **hormonal deficiency**, not a structural one that would be addressed by vaginoplasty first. *Clitoroplasty* - **Clitoroplasty** is a surgical procedure to reduce the size of an enlarged clitoris, usually performed in cases of **ambiguous genitalia** or **congenital adrenal hyperplasia**. - There is no indication of clitoromegaly or ambiguous genitalia in this patient's presentation; her primary issue is the absence of puberty. *B/L gonadectomy* - **Bilateral gonadectomy** is indicated in patients with **Y chromosome material** and **gonadal dysgenesis** (e.g., Swyer syndrome or mixed gonadal dysgenesis) due to the high risk of **gonadoblastoma**. - While this patient has **gonadal dysgenesis** associated with **Turner syndrome**, she lacks a **Y chromosome**, meaning the risk of malignant transformation in her streak gonads is low, and therefore prophylactic gonadectomy is not typically performed.

Question 4: Which of the following conditions is least likely to present with ambiguous genitalia?

A. Hermaphroditism
B. Super female (47 XXX) (Correct Answer)
C. Gonadal dysgenesis
D. Gonadal agenesis

Explanation: ***Super female (47 XXX)*** - Individuals with **47,XXX syndrome**, often called "triple X syndrome," typically have a **normal female phenotype** and are not usually born with ambiguous genitalia. - While they may have some developmental differences or fertility issues, their external genitalia are typically **unambiguously female**. *Gonadal dysgenesis* - This condition involves **abnormal development of the gonads**, leading to a spectrum of presentations that can include **ambiguous genitalia**. - Incomplete differentiation of the testes or ovaries can result in external genitalia that are neither definitively male nor female. *Hermaphroditism* - **True hermaphroditism** (now referred to as **ovotesticular disorder of sex development**) is characterized by the presence of **both ovarian and testicular tissue** in the same individual. - This condition almost always results in **ambiguous external genitalia** because the sex hormone production is mixed. *Gonadal agenesis* - **Gonadal agenesis** refers to the **complete absence of gonads**, which can lead to ambiguous genitalia, particularly if gonadal development failed before external genitalia differentiation. - Without the hormones produced by the gonads (e.g., androgens from testes), the development of male external genitalia is impaired, leading to **under-masculinization** or ambiguous features.

Question 5: Congenital adrenal hyperplasia most commonly presents as

A. 46,XY DSD
B. Ovotesticular DSD
C. 46,XX DSD with virilization (Correct Answer)
D. 46,XY DSD with undervirilization

Explanation: ***46,XX DSD with virilization*** (formerly female pseudohermaphroditism) - This is the **most common presentation** of congenital adrenal hyperplasia (CAH), particularly due to **21-hydroxylase deficiency**, which accounts for >90% of CAH cases. - Affects genetically female (46,XX) individuals with excess **androgens** produced by hyperplastic adrenal glands leading to **virilization** of external genitalia. - Clinical features include **clitoromegaly, labioscrotal fusion**, and varying degrees of masculinization, while **internal female organs (uterus, ovaries, fallopian tubes) remain normal**. - This is the classic presentation that brings CAH to clinical attention in newborn screening programs. *46,XY DSD* (formerly 46,XY intersex) - This terminology refers to conditions where genetically male individuals (46,XY) have atypical genital development. - Common causes include **androgen insensitivity syndrome** or disorders of testosterone synthesis (5α-reductase deficiency, 17β-hydroxysteroid dehydrogenase deficiency). - CAH in 46,XY individuals typically presents with **isosexual precocious pseudopuberty** (early virilization) in simple virilizing forms or **salt-wasting adrenal crisis** in severe forms, not undervirilization. *Ovotesticular DSD* (formerly true hermaphroditism) - Very rare condition where an individual has **both ovarian and testicular tissue**, either as separate gonads or combined as ovotestes. - Often involves complex chromosomal patterns including **46,XX/46,XY mosaicism** or 46,XX with SRY translocation. - Not related to CAH pathophysiology, which involves enzymatic defects in steroidogenesis. *46,XY DSD with undervirilization* (formerly male pseudohermaphroditism) - Occurs when 46,XY individuals have **undervirilized or ambiguous external genitalia** due to impaired androgen synthesis or action. - Causes include disorders of testicular development, androgen biosynthesis defects, or **androgen insensitivity**. - While CAH can affect males, it causes **excess androgens** leading to precocious puberty, not undervirilization.

Question 6: A 10 day old male pseudohermaphrodite child with 46 XY karyotype presents with BP of 110/80 mmHg. Most likely enzyme deficiency is:

A. 17 hydroxylase (Correct Answer)
B. 3-beta hydroxylase
C. 11 hydroxylase
D. 21 hydroxylase

Explanation: ***17-hydroxylase*** - Deficiency of **17α-hydroxylase** leads to impaired synthesis of androgens and estrogens, resulting in **male pseudohermaphroditism** (46 XY DSD) [1]. - The block in cortisol and sex steroid synthesis shunts precursors toward mineralocorticoid production (e.g., **corticosterone, deoxycorticosterone**), causing **hypertension** and **hypokalemia** [1]. *3-beta hydroxysteroid dehydrogenase* - This deficiency affects the synthesis of all three classes of adrenal steroids (glucocorticoids, mineralocorticoids, and androgens). - It would typically lead to **salt wasting**, **hypotension**, and severe **masculinization in females** or **pseudohermaphroditism in males**, but without hypertension. *11-hydroxylase* - Deficiency of **11β-hydroxylase** leads to accumulation of **11-deoxycorticosterone** (DOC) and **11-deoxycortisol**, which have mineralocorticoid activity. - This causes **hypertension** and **virilization** (overproduction of weak androgens), but it does not cause male pseudohermaphroditism. *21-hydroxylase* - This is the most common form of **congenital adrenal hyperplasia** (CAH) and results in impaired synthesis of cortisol and aldosterone, leading to an accumulation of androgen precursors. - Clinical features include **virilization in females**, **salt wasting** (due to aldosterone deficiency), and **hypotension** rather than hypertension in the severe forms, and no DSD in males.

Question 7: A teenage girl presents with a history of amenorrhea. Local examination is shown in the image. What karyotype analysis would you consider for further evaluation?

A. 46 XY
B. 46 XX
C. 45 XO (Correct Answer)
D. 47 XXY
E. 47 XXX

Explanation: ***45 XO*** - The image shows a **webbed neck** and **short stature** (suggested by the overall body proportions typically associated with Ullrich-Turner Syndrome), alongside primary amenorrhea, which are classic features of **Turner Syndrome**. - **Turner Syndrome** is a chromosomal disorder characterized by the absence of all or part of one X chromosome in females, resulting in a **45, XO karyotype**. *46 XY* - This karyotype indicates a **phenotypic male** with normal male chromosomal constitution. - Individuals with this karyotype would not typically present with **primary amenorrhea** as they do not have a uterus. *46 XX* - This is the **normal female karyotype**, and while a female with this karyotype could experience amenorrhea (e.g., due to Asherman's syndrome or PCOS), the physical features associated with the image (like webbed neck) are not consistent. - This option does not explain the **physical stigmata** often seen in genetic causes of primary amenorrhea, such as in Turner syndrome. *47 XXY* - This karyotype is characteristic of **Klinefelter Syndrome**, which affects males and is associated with hypogonadism and gynecomastia. - It would not be found in a female patient presenting with **amenorrhea** and the physical features shown in the image. *47 XXX* - This karyotype represents **Triple X Syndrome** (Trisomy X), which affects females and typically presents with **normal female appearance** and often normal fertility. - While some individuals may have menstrual irregularities, the **distinctive physical features** shown in the image (webbed neck, short stature) are not characteristic of Triple X syndrome, which usually lacks specific dysmorphic features.

Question 8: A 16-year-old girl comes to you with primary amenorrhea; on evaluation there is absent breast development, she has a normal stature, her FSH and LH levels are found to be high and she has a karyotype of 46XX. What is the probable diagnosis?

A. Testicular feminizing syndrome
B. Turner syndrome
C. Kallmann syndrome
D. Gonadal dysgenesis (Correct Answer)

Explanation: ***Gonadal dysgenesis*** - **Primary amenorrhea** with **absent breast development** and **high FSH/LH** (hypergonadotropic hypogonadism) in a **46,XX individual** with **normal stature** points to **46,XX gonadal dysgenesis** (pure gonadal dysgenesis). - In this condition, the gonads fail to develop properly despite a normal female karyotype, leading to non-functional streak ovaries that fail to produce estrogen, hence the lack of secondary sexual characteristics and elevated gonadotropins due to lack of negative feedback. - Unlike Turner syndrome, patients have normal stature and a normal 46,XX karyotype. *Testicular feminizing syndrome* - Individuals with **complete androgen insensitivity syndrome (CAIS)**, formerly called testicular feminizing syndrome, have a **46,XY karyotype** and develop external female characteristics due to complete androgen resistance. - They present with **primary amenorrhea** but typically have **well-developed breasts** (from peripheral aromatization of testosterone to estrogen) and a blind-ending vagina, which contradicts the absent breast development in this case. *Turner syndrome* - Characterized by a **45,X karyotype** (or variants with mosaicism) and typically presents with **short stature**, primary amenorrhea, and gonadal dysgenesis. - While it causes **primary amenorrhea** and **absent breast development** with high FSH/LH, the **normal stature** and **46,XX karyotype** in this patient rule out Turner syndrome. *Kallmann syndrome* - This condition is characterized by **hypogonadotropic hypogonadism** associated with **anosmia or hyposmia** due to defective GnRH secretion. - Patients present with **low FSH and LH levels**, which contradicts the **high gonadotropin levels** seen in this case.

Question 9: An eight-year-old girl presented by her mother with sexual precocity. She may have the following disorder:

A. Addison's disease
B. Neuroblastoma
C. Hyperthyroidism
D. McCune Albright syndrome (Correct Answer)

Explanation: ***McCune Albright syndrome*** - This syndrome is characterized by a triad of **fibrous dysplasia**, **café-au-lait spots**, and **precocious puberty**, which fits the clinical picture of an 8-year-old girl with sexual precocity. - The precocious puberty in McCune-Albright syndrome is typically **gonadotropin-independent**, meaning it originates from the ovaries due to overactivity rather than pituitary stimulation. *Addison's disease* - Addison's disease involves **adrenal insufficiency**, leading to symptoms like fatigue, weight loss, and hyperpigmentation, but it typically does not cause sexual precocity. - It would be associated with low **cortisol** and high **ACTH** levels, which are not indicative of premature sexual development. *Neuroblastoma* - **Neuroblastoma** is a childhood cancer that can cause symptoms due to catecholamine secretion or mass effect, but it does not directly cause sexual precocity. - While it can be associated with paraneoplastic syndromes, precocious puberty is not a typical manifestation. *Hyperthyroidism* - **Hyperthyroidism** in children can present with symptoms like weight loss, tachycardia, and goiter, but it is not a direct cause of sexual precocity. - While thyroid hormones influence growth and development, they do not typically trigger premature pubertal changes.

Question 10: In Precocious puberty, the age limit for girls is?

A. 8 years (Correct Answer)
B. 10 years
C. 9 years
D. 11 years

Explanation: ***8 years*** - Precocious puberty is defined clinically by the development of secondary sexual characteristics in girls before the age of **8 years old**. - This age cut-off is based on population studies and clinical consensus to identify children needing further evaluation for underlying causes. *10 years* - This age is generally considered within the **normal range** for the onset of puberty, not precocious. - Pubertal development typically begins between ages 8 and 13 in girls. *9 years* - While close to the precocious threshold, **9 years** is still considered within the typical window for the onset of puberty. - The established clinical definition for precocious puberty in girls is explicitly _before_ the age of 8. *11 years* - This age is well within the **normal range** for pubertal onset and progression in girls. - Development of secondary sexual characteristics at this age would not be considered precocious.

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