A 6-year-old girl is brought to the office for evaluation of pubic hair development. The girl's mother reports first noticing axillary hair a few weeks ago while dressing her for school. The patient has also had breast and pubic hair development but no vaginal bleeding, headaches, emesis, or visual disturbances. She has no medical conditions and takes no daily medications. The patient had 2 long bone fractures at ages 4 and 5. Family history is unremarkable. Physical examination reveals 2 large hyperpigmented macules with irregular contours on the left side of her back and chest. Axillae have secondary hair; there is no freckling. Bilateral breasts have budding and enlargement of the areola. There is coarse, dark pubic hair along the labia and the pubic junction. Which of the following is the most likely diagnosis in this patient?
Show Explanatory Sources
This child has early breast and pubic hair development consistent with precocious puberty, the onset of secondary sexual characteristics in girls age <8 or boys age <9. Central precocious puberty is due to early activation of the hypothalamic-pituitary-gonadal axis. Peripheral precocity is attributed to premature secretion of sex hormones independent of GnRH.
In addition to precocious puberty, this patient has irregular café-au-lait macules confined to one side of the body and recurrent fractures due to polyostotic fibrous dysplasia, characteristic of McCune-Albright syndrome (MAS). MAS is a rare cause of precocious puberty due to a mutation in the GNAS gene, which results in constant G protein activation and overproduction of pituitary hormones. Therefore, in addition to GnRH-independent (ie, peripheral) precocious puberty (FSH, LH), MAS can also lead to thyrotoxicosis (TSH), acromegaly (GH), and Cushing syndrome (ACTH).
(Choice A) An adrenal tumor typically causes isolated premature adrenarche (eg, pubic/axillary hair, acne, body odor) and is unlikely in this patient with concomitant breast development.
(Choice C) Neurofibromatosis type 1 (NF1) can cause precocious puberty (due to optic glioma affecting the hypothalamus) and long-bone dysplasia (eg, fractures). However, café-au-lait macules in NF1 are typically more numerous (≥6) with regular borders and have associated axillary freckling.
(Choice D) Peutz-Jeghers syndrome is characterized by gastrointestinal tract hamartomatous polyposis. The associated skin lesions are small (1-5 mm), perioral, mucocutaneous pigmented macules. Patients do not undergo precocious puberty.
(Choice E) Sturge-Weber syndrome is characterized by intellectual disability, seizures, and visual impairment due to capillary-venous malformations. The associated skin lesion is a port-wine stain over the territory of the trigeminal nerve. There is no associated precocious puberty.
(Choice F) Tuberous sclerosis is a neurocutaneous disorder that can cause central precocious puberty due to brain hamartomas. However, associated skin lesions include hypopigmented ash-leaf spots and shagreen patches.
Educational objective:
McCune-Albright syndrome is characterized by peripheral precocious puberty, irregular café-au-lait macules, and polyostotic fibrous dysplasia (eg, recurrent fractures).