7291 From Vaginal Bleeding to Genetic Complexity: McCune Albright Syndrome in a Toddler; Emphasizing Atypical Manifestations, Diagnostic Challenges, and Comprehensive Management
Authors: Martinez Sanchez Andrea G , Fernandez Natalie , Bustamante Escobar Carmen L 
Published: October 2024

Disclosure: A.G. Martinez Sanchez: None. N. Fernandez: None. C.L. Bustamante Escobar: None.

Background: McCune Albright Syndrome (MAS) is a rare genetic disorder characterized by a triad of peripheral precocious puberty, irregular café-au-lait spots, and bone fibrous dysplasia. It is often caused by post-zygotic somatic mutations in the GNAS1 gene. We present a case of a patient initially presenting with precocious puberty, whose diagnostic journey revealed MAS with atypical manifestations. Presentation: A 23-month-old girl was brought to the emergency department after her mother noticed vaginal bleeding during a diaper change; denied any trauma, fever, rash, or dysuria. Patient developed accelerated growth about six months earlier, followed by pubic hair three months prior and bilateral thelarche two weeks before presentation. The patient had no exposure to endocrine disruptors. The physical examination revealed a well-developed child, in the 92nd percentile for weight and 97th for height. Additionally, breast buds, fine hair on the labia, and minimal blood at the vaginal introitus, with no apparent signs of trauma. Initial laboratory findings showed prepubertal LH and FSH levels, elevated estradiol 120 pg/ml (prepubertal range &lt;10) and advanced bone age (4.2 years). Normal levels of testosterone, 17-hydroxyprogesterone, and DHEA sulfate. Pelvic ultrasound demonstrated an enlarged uterus (5.6 x 1.8 x 2.4 cm) and a large cystic lesion (4.4 cm) on the right ovary. During a follow-up at the endocrinology department one week later, a meticulous examination identified an irregular café-au-lait spot measuring about 2cm over the occipital right side of her scalp. Further tests, including GnRH stimulation test, tumor markers (LDH, b-HCG, CEA, and Ca19-9), brain MRI and bone scan, yielded normal findings. Given the presentation consistent with Peripheral precocious puberty, Letrozole was initiated at 1.25 mg daily. Three months later, her growth velocity remained accelerated. However, there was a decrease in both breast tissue and uterus size (4.2 x 1.2 x 1.7 cm), and the ovarian cyst was resolved. Genetic testing in blood indicated no mutations. To conduct a thorough assessment, the insulin-like growth factor (IGF-1) level was measured and found to be 200 ng/mL (normal range 56-144 ng/mL). Unfortunately, obtaining prolactin levels was challenging due to difficult intravenous (IV) access. Conclusion: This case reveals the complexity of MAS in precocious puberty, emphasizing atypical features that add complexity to the diagnosis. Identifying an irregular café-au-lait spot served as a diagnostic indicator, revealing the diverse clinical presentations. The challenges of relying solely on genetic testing for diagnosis are evident due to the mosaic nature and tissue-specific distribution of the mutation, as highlighted by the absence of mutations in this patient. Long-term management requires ongoing monitoring and a multidisciplinary approach for optimal patient outcomes.

Presentation: 6/1/2024