Endocrine Abstracts

JOINT3481

Introduction: Congenital hypogonadotrophic hypogonadism (CHH) is a rare condition with heterogeneous clinical findings resulting from inadequate secretion of normal pulsatile gonadotropin-releasing hormone (GnRH). More than 50 genes have been reported to cause delayed puberty or infertility. Isolated HH/Kallman syndrome cases reported with SPRY4 gene mutation are quite rare in the literature. Here, a case of short stature complaint and heterozygous variant detected in SPRY4 gene is presented.

Case Presentation: A 14.3-year-old male patient applied to the pediatric endocrinology clinic with a complaint of short stature. The patient, who was born at term with a birth weight of 3400 grams, had hypospadias surgery at the age of 7. The patient’s neuromotor developmental stages were normal and there was a history of distant consanguinity between the parents. In his physical examination, body weight: 54 kg (-0.42 SDS), height: 150 cm (-2.23 SDS), bone age: 12.7-year-old; testicular volumes 2ml/2ml, penis length: 3.5 cm (<10p), coronal hypospadias, pubis stage 2, no axillary hair. The patient, whose basal FSH and LH values were low, underwent LHRH stimulation test and was observed to have pih FSH: 2.51 mIU/mL, peak LH: 0.58 mIU/mL T. testosterone: <0.025 ng/mL. The patient’s other anterior pituitary hormone levels were within normal range, Inhibin B: 87.1 pg/mL (169-216), IGF1: 121 ng/mL (177-507), IGFBP3: 3.30 mg/l (3.5-10). The patient had no findings of synkinesis and anosmia, and bilateral sensorineural hearing loss was detected in the hearing test. Renal ultrasonography showed double collecting systems in both kidneys, and pituitary MRI showed partially empty sella. Lumbar BMD Z score (corrected for height): -1.95. Karyotype: 46, XY, and WES analysis revealed c.203G>A heterozygous variant in the SPRY4 gene. It was found to be compatible with hypogonadotropic hypogonadism with/without anosmia 17 (OMIM: 615266). The patient was started on physiological induction hormone replacement therapy with hCG + FSH protocol.

Conclusion: SPRY4 gene, which encodes a member of SPRY family, is located in 5q31.3 location region. In addition to being in the FGF8 synexpression group, it is also an inhibitor of the RAS-MAPK pathway. Hypogonadotrophic hypogonadism (with/without anosmia), craniofacial defects, dental anomalies, hearing disorders, bone mineral disorders have been reported in this rare SPRY4 gene mutations.