ESPE Abstracts

Background: Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disorder caused by NF1 mutation. The condition is typified by the development of benign and malignant tumours in both the central nervous system and peripheral tissues. We present two siblings diagnosed with NF1 who presented at an early age with isolated menarche.

Case Presentation: Sibling 1 – A 7-year-old patient was referred with concerns regarding recurrent cyclical vaginal bleeding for 3 months. Bleeding was moderate and typically lasted 2-3 days. On examination the patient was prepubertal (P1, B1, A1) with no evidence of focal neurological deficit. Examination under anaesthetic of the genitalia identified no focal cause of the bleeding. The patient had been diagnosed with NF1 at 4 years of age based on family history, multiple café au lait spots and an MRI scan showing a 15 x 11 x 10mm optic glioma. She required no medications and had mild learning difficulties. A gonadotropin releasing hormone (GnRH) test showed a prepubertal response (FSH peak 9.7 IU/L, LH peak 3.4 IU/L) and ultrasound of the pelvis revealed pre-pubertal uterine and ovarian appearances. The patient was managed conservatively and puberty was established at 12 years of age.

Sibling 2 – Five years later the 6-year-old sister of patient 1 presented with recurrent cyclical vaginal bleeding. On examination the patient was prepubertal. Further assessment under anaesthetic showed no focal cause of bleeding. The patient had been diagnosed with NF1 at 2 years of age based upon family history and cutaneous lesions. Serial cranial MRI scans were normal. Her GnRH test showed FSH dominant response (LH peak 3.5 IU/L, FSH peak 9.4 IU/L). Pelvic ultrasound showed ovarian volumes of 0.5ml and 0.7ml with a pre-pubertal uterus without an endometrial echo. The patient was managed conservatively and remains under active follow-up.

Conclusion: NF1 associated optic glioma has been previously associated with central precocious puberty. We describe two siblings with a clear history of premature isolated menarche but no evidence of central precocious puberty. Although the mechanism causing isolated menarche has not been established, this is an important association and adds to the understanding of phenotypes associated with NF1.