A Family with Novel X-linked recessive Homozygous mutation in ANOS-1 gene (c.628_629 del, p.1210fs*) in Kallmann syndrome associated unilateral ptosis; A case report and review of the literature.

Abstract Objectives Kallmann syndrome (KS) may be accompanied by anosmia or hyposmia and midline defects. Herein, we presented an overweighed 16-year-old boy with a lack of puberty, anosmia, congenital right-eye ptosis, and normal intellectual function. Ptosis is a rare finding in KS literature. Methods Testicular ultrasonography was performed. Whole Exon Sequencing was performed on peripheral blood specimens. Genetic results were confirmed by Sanger sequencing. Anosmia was evaluated by a quantitative method using KVSS Test II. Results A 16-year-old patient presented with a complaint of lack of body hair growth and small penile size with no remarkable past medical history. He was the second son of third-degree consanguineous healthy parents. Physical examination revealed pubertal Tanner Stage I. Congenital right eye ptosis and obesity were other findings in the examination. Besides, anosmia was confirmed using KVSS Test II. Sexual hormone profile was testosterone=135 ng/dl (normal>300 ng/dl), FSH=0.16 and LH=0.86 IU/L (normal age-gender adjusted:0.3-10, and 1.5-8 IU/L, respectively). Further, an X-linked recessive Homozygous mutation, c.628_629 del (p.1210fs*), in exon-5 of the ANOS-1 gene was revealed. Same mutation in two other members of the family, patient’s uncle and great uncle, on the mother's side were found. Conclusion To date, approximately 28 ANOS-1 mutations, producing KS phenotypes, have been described; but, to the best of our knowledge, this X-linked recessive mutation has not been previously reported in KS. Identification of these cases increases awareness of the phenotypic heterogeneity in the novel forms of Kallmann syndrome, so early definitive treatment can be expedited, which may prevent the development of further complications