Abstract
Introduction: Turner syndrome (TS) occurs due to loss of either all or part of the X chromosome, in some or all the cells of the body. The most consistent features of TS are short stature and premature ovarian failure. Neurofibromatosis type 1 (NF1) is an inheritable in an autosomal dominant manner tumor predisposition syndrome and is caused by loss-of-function mutations in the tumor suppressor NF1 gene (neurofibromin 1). Literature review indicated rare cases with NF1 and TS (1). We report the sixth girl with mosaic TS and NF1 who presented with optic nerve glioma.
Case report: A 2-year-old female presented to us due to short stature. Her height was 2,5 SD lower than the mean parental height curve, and her bone age was delayed only by 3 months. She already had a normal (46XX) peripheral blood karyotype (70 mitoses). She had abnormal body proportions and with short limbs with unremarkable café au lait spots. Additionally, to the short stature laboratory investigation we ordered a gene panel to exclude hypochondroplasia, and a Karyotype in fibroblasts culture from oral cavity sample. The results revealed low IGF-1 and mosaic TS in 14%. We preformed 2 provocative tests which revealed low growth hormone peak < 5 ng/ml. A brain and pituitary MRI to exclude pituitary lesions or structural abnormalities revealed gliomas of the optic chiasma and the right optic nerve with characteristic NF1 “spots” (regions of signal abnormality in T2 sequences) involving the basal ganglia, cerebellum and the right temporal lobe. DNA sequencing targeted to a gene panel related to NF1 and NF2 revealed a novel de novo heterozygous NF1 gene mutation in exon 28 [3764Α>G];[=]p.[Gln1255Arg].
Discussion: NF1- Gliomas are most commonly seen in young children, (mean 4.5 years). Only 1/3 of affected children will require therapeutic intervention. However early diagnosis, of optic gliomas is important. Our patient was completely asymptomatic by the time of diagnosis and no other symptom or sign of NF1 was apparent. Ophthalmologic examination was normal, but visual electrophysiologic testing was abnormal as far the right optic nerve is concerned. The oncology team decided to preform chemotherapy. In TS impaired growth is related to resistance in GH. Some studies suggested that there could be a relationship between GHD and NF1 even in the absence of an organic pituitary damage. In our patient it has been decided not to treat with GH and closely track the patient’s growth.
Conclusion: Coexistence of NF1 with TS is rare. Awareness is needed as early identification and treatment of CNS gliomas can prevent visual loss and severe co-morbidities.
1.
Rare Presentation of Neurofibromatosis and Turner Syndrome in a Pediatric Patient. Pediatr Rep. 2017 Jun 26; 9(2): 6810
Neurofibromatosis Type 1 with Overlap Turner Syndrome and Klinefelter Syndrome