A 15-year-old girl is brought to the office for evaluation of primary amenorrhea. The patient's mother and older sisters underwent menarche around age 13. The patient has had no changes in weight or nipple discharge but has difficulty identifying various odors. She has no known medical conditions and has had no surgery. The patient takes no daily medications and does not use tobacco, alcohol, or illicit drugs. She is not sexually active. Height is at the 3rd percentile for age, with 4.8 cm (1.9 in) of growth noted in the last year. Visual fields are intact. No breast tissue is present, and there is no axillary or pubic hair. Ultrasound confirms the presence of a uterus and 2 normal-appearing ovaries. Serum FSH level is 2 mU/mL (normal: 4-30 mU/mL) and LH is 3 mU/mL (normal: 5-25 mU/mL). Karyotype analysis of this patient is most likely to show which of the following?

Question

A 15-year-old girl is brought to the office for evaluation of primary amenorrhea.  The patient's mother and older sisters underwent menarche around age 13.  The patient has had no changes in weight or nipple discharge but has difficulty identifying various odors.  She has no known medical conditions and has had no surgery.  The patient takes no daily medications and does not use tobacco, alcohol, or illicit drugs.  She is not sexually active.  Height is at the 3rd percentile for age, with 4.8 cm (1.9 in) of growth noted in the last year.  Visual fields are intact.  No breast tissue is present, and there is no axillary or pubic hair.  Ultrasound confirms the presence of a uterus and 2 normal-appearing ovaries.  Serum FSH level is 2 mU/mL (normal: 4-30 mU/mL) and LH is 3 mU/mL (normal: 5-25 mU/mL).  Karyotype analysis of this patient is most likely to show which of the following?

Quizplus · Accepted Answer

11ec25c8_d6e0_3eca_bc81_63b4e70e114a_MD0003_00 Delayed puberty is diagnosed based on the lack of secondary sexual characteristics in girls age ≥12. This patient's pubertal delay and anosmia (ie, inability to distinguish odors) are suggestive of Kallmann syndrome, a disorder of migration of fetal olfactory and GnRH-producing neurons, resulting in rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Most cases are X-linked recessive; however, girls can be affected via sporadic, autosomal dominant, and autosomal recessive mutations. Due to the lack of GnRH production and release from the hypothalamus, the pituitary does not release gonadotropins; therefore, patients have low FSH and LH levels. The low gonadotropin levels do not stimulate the ovary to produce estrogen; therefore, girls have short stature, primary amenorrhea, and no breast development. Boys and girls have a karyotype/genotype consistent with phenotype (46,XX in this girl) and normal internal reproductive organs. Management of these patients includes facilitating development of secondary sexual characteristics in adolescents and improving fertility in adults. (Choice A) Patients with Turner syndrome (45,XO) are phenotypically female and may present with delayed puberty (eg, short stature, no breast development, amenorrhea). However, due to gonadal dysgenesis and resultant primary ovarian insufficiency, patients have hypergonadotropic hypogonadism (elevated FSH and LH). Turner syndrome (Choice C) Patients with androgen insensitivity syndrome (AIS) or 5-alpha-reductase deficiency are genotypic males (46,XY) who present as phenotypic females. Patients with AIS have breast development but no pubic and axillary hair. Patients with 5-α-reductase deficiency have virilization (eg, clitoromegaly) at puberty and no breast development. In both cases, patients have primary amenorrhea (no uterus) but normal to high FSH and LH levels. (Choice D) Patients with a 47,XXX genotype typically have normal secondary sexual characteristic development and tall stature. FSH and LH levels are normal. (Choice E) Patients with Klinefelter syndrome (47,XXY) are phenotypically male and present with hypergonadotropic hypogonadism (elevated FSH and LH) due to testicular damage during development. Klinefelter syndrome Educational objective: Kallmann syndrome is a disorder of migration of fetal GnRH and olfactory neurons that results in delayed puberty (ie, primary amenorrhea) and anosmia. Due to the lack of GnRH secretion, patients have hypogonadotropic hypogonadism (low FSH). In these patients, karyotype (genotype) is consistent with phenotype. References: Isolated gonadotropin-releasing hormone (GnRH) deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/20301509) Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. (http://www.ncbi.nlm.nih.gov/pubmed/29108899)

A 15-Year-Old Girl Is Brought to the Office for Evaluation