Background: Kallmann syndrome (KS), the prototype of anosmic idiopathic hypogonadotropic hypogonadism (IHH), is charecterized with HH acompanied by anosmia, absence or hypoplasia of olfactory bulbus due to defective morphogenesis. Mutations in 10 genes have been reported to cause KS while can clarify the underlying molecular defect in about 3050% of IHH/KS cases. Beside, PROK2 gene mutations are extremely rare cause of KS. Herein, we present KS due to a homozygous missense c.217C>T(p.R73C) mutation detected in exon-2 of the PROK2 gene in a consanguineous Turkish family.
Case report: The index case was a 13 year-old male presented with delayed puberty and small penis. His past medical history was unremarkable. Parents were first cousin. In the physical examination his height was 143.1 cm (25th pc.), weight was 37.4 kg (25th pc.). His genitourinary system examination revealed a penis size of 4 cm, a left testis of 2 ml in the scrotum with a non-palpable right testis. He had anosmia. Hormonal work/up revealed prepubertal gonadotropin levels with undetectable testosterone (FSH:0.546 mIU/ml, LH:0.13 mIU/ml, total testosterone:<20 ng/dl). Ultrasonographic examination showed a 10×5×5 mm testis on right inguinal canal and left testis in the scrotum. A dagnosis of KS was considered and right orchiopexy had been performed. Molecular genetic analysis detected a previously reported homozygous missense c.217C>T (p.R73C) mutation in the exon-2 of PROK2 gene. A prepubertal male sibling was also homozygous for the mutation. His clinical and laboratory investigations are still in process. Unaffected parents, three males and one female siblings were heterozygous for the mutation.
Conclusion: Since KS due to PROK2 gene mutations is extremely rare, present family with case(s) having clinical characteristics of KS and homozygous missense c.217C>T(p.R73C) mutation in PROK2 gene and those who were unaffected and heterozygous for the mutation would help to further understand the underlying molecular genetics etiology of KS.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology