Endocrine Abstracts

JOINT2890

Background: Clitoromegaly in infant girls is usually related with conditions from the Disorders of sexual development (DSD) spectrum but can also be an unusual manifestation of other diseases such as Neurofibromatosis type 1 (NF1). NF1 is a rare autosomal-dominant disorder caused by heterozygous mutations in NF1 gene; 50% of the cases are de novo. Phenotype includes café-au-lait spots, axillary and/or inguinal freckling, increased susceptibility for development of benign/malignant tumors in peripheral nerves, etc., but in sporadic cases a clitoromegaly was also reported.

Case presentation: The index patient is a 5.5-years-old girl referred for genetic testing due to a progressive enlargement of the clitoris during the last year. The child was assigned as a female with no other signs of virilization but with growth delay and few café-au-lait spots from the birth. Retrospectively, a positive family history for hyperpigmented café-au-lait spots and short stature was announced in mother and maternal grandfather with no other severe presentations of Neurofibromatosis. The laboratory tests in proband revealed normal thyroid function, normal levels of androgens and gonadotropins and 46, XX karyotype. DNA from venous blood was extracted from the patient and her parents and Whole exome sequencing (WES) was performed with targeted analysis of genes associated with DSD and NF. A heterozygous pathogenic variant NF1:c.7348C>T, p.Arg2450Ter was identified in the patient; the subsequent Sanger sequencing revealed the maternal origin of the mutation. Additionally, a prenatal diagnosis was advised in the current pregnancy in the family and a heterozygous mutation was detected in the male fetus. However, family decided to continue with the pregnancy and a boy was born at term without complications. Both children are currently on close monitoring from skilled pediatric endocrinologist in order to pursue the clinical presentation and effective treatment to be provided on time.

Conclusions: The use of advanced genetic tests might be very helpful in cases with complex presentation. Determination of correct genotype-phenotype correlations is of high importance in precise diagnosis, better follow-up and clinical management of such heterogeneous conditions as NF1 with non-typical clinical features.