Poster Abstract Abstract
A family with hypogonadotropic hypogonadism and novel variant of FGFR1 gene mutation
Mazidah Noordin, Department of Paediatrics, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Selangor; Muhammad Yazid Jalaludin, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur; Azriyanti Anuar Zaini, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur; Nurshadia Samingan, Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur; Meenal Mavinkurve, Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur; Ahmad Fahmi Abdullah Asuhaimi, Department of Paediatrics, Hospital UiTM, 42300 Bandar Puncak Alam, Selangor; Noor Shafina Mohd Nor, Department of Paediatrics, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Selangor
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FGFR1 gene mutation is a known cause of gonadotropin deficiency such as Kallmann syndrome. We described two cases in a non-consanguineous family, with a variant of FGFR1 gene mutation presented as under-virilized males. Both patients have normal sense of smell.
A 9-month-old boy presented with history of ambiguous genitalia at birth. He had signs of under-virilization at birth including micropenis with stretched penile length of 1.7 cm, and bilateral undescended testes. He was planned for workup, but the parents defaulted until current presentation. Karyotype confirmed 46, XY with SRY gene detected. hCG stimulation test revealed poor testosterone rise. LHRH test did not show a response to GnRH. Genetic mutation analysis revealed FGFR1 mutation variant at position c.1430.
His paternal uncle, a 13-year-6-month teenage boy was also referred to us for micropenis. He was not dysmorphic. He had no signs of puberty. Genitalia examination revealed micropenis with stretched penile length of 2.5 cm, and prepubertal testicular volume bilaterally. Karyotype confirmed 46, XY with SRY gene detected. He had low baseline levels of LH, FSH, and testosterone. Both hCG and LHRH tests showed poor pituitary and gonadal response. MRI showed normal pituitary gland and olfactory bulbs. He has the exact mutation variant at FGFR1 gene as the index case.
Both of our patients shared common features of under-virilization and biochemical evidence of hypogonadotropic hypogonadism. Despite there being more than 200 missense mutations of the FGFR1 gene reported in “The Human Gene Mutation Database” and the “ClinVar” database, the genetic mutation variant that our patients shared was not registered in both databases and may suggest a novel mutation associated with hypogonadotropic hypogonadism. Identification of genetic diagnosis may assist in proper counseling for the patients and family.