IMPE Abstracts

Introduction: NF1 is autosomal dominant disorder that is caused by mutation in NF1 gene, known as “NEUROFIBROMIN” which acts as inhibitor of oncogene RAS. . NF1 has wide variety of association in context with puberty, only few cases are reported in Pakistan with different variety of pubertal growth in association with NF1.

Cases: we present two cases of NF1 with pubertal variation that presented to our pediatric endocrinology department l, in which we have describe the diversity of clinical presentation of NF1 with diagnostic challenges.

Case 1: A 19 years old female presented with large swelling over back (Plexiform Neurofibroma), multiple cafe’-au-lait spots and neurofibromas on different parts of body. She was developmentally normal, short heighted and having kyphoscoliotic deformity. Genital examination reveals normal female genetalia with tanner staging [B1, A1, P1=0] with absence of axillary hair. She was investigated extensively in the regards of NF1 and delayed puberty in the form of MRI brain which reveled pituitary microadenoma. Ultrasound pelvis showed slit like uterus and streak ovaries. Serum FSH, and LH was too much high, with decrease level of serum estrogen and IGF-1. Bone age was less than chronological age. This hypergonandotrophic hypogonadism type of delayed puberty was managed by hormonal replacement therapy by tablet ethinyl estradiol and referred to orthopedic surgeon for the management of kyphoscoliotic deformities.

Case 2: An eight years old male child presented with multiple cafe’-au-lait spots on back and typical signs of precocious puberty. He was developmentally delayed having decreased visual acuity. On genital examination he has bilateral testicular volume of 7 ml, penile length was 6 cm and dark pigmented genitalia with more dense, coarse and curly pubic hair with tanner staging of IV. MRI brain with pituitary protocol showed bilateral optic pathway gliomas with FASI (Focal areas of signal hyper intensity) strongly suggestive of neuroimaging feature of NF1. Bone age was advanced and his hormonal analysis shows markedly elevated levels of LH, FSH, prolactin, and testosterone. While serum cortisol and thyroid profile was unremarkable. His genetic mutation reviled pathogenic heterozygous mutation of NF1 gene with variant (c. 1756_1759del). He was then treated with GnRH analog, Inj Lectrum every monthly. On follow up visits after six months of treatment his testicular volume, penile length and pubic hair growth hair was reduced.

Conclusion: Growth and puberty present in unusual diversity with NF1 which poses challenges in diagnosing and management.