KAL1 유전자의 완전 결실로 인해 형제에서 발생한 칼만 증후군
A Familial Case of Kallmann Syndrome due to KAL1 Gene Complete Deletion
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칼만 증후군은 성선 자극 호르몬 결핍성 성선기능 저하증과 무후각증을 동반하는 것을 특징으로 하는 질환으로 대부분 산발적으로 발생하지만 유전적으로 발생하는 경우도 있으며 여기에는 성염색체 연관성으로 유전되는 KAL1 유전자 돌연변이, 상염색체 우성으로 유전되는 KAL2 유전자 돌연변이, 상염색체 열성으로 유전되는 KAL3 유전자 돌연변이가 있다. 저자들은 사춘기 지연과 잠복 고환을 주소로 성선 기능 저하증이 의심되는 형제에서 보인자인 어머니에게서 유전된 KAL1 유전자의 완전 결실로 인한 칼만 증후군을 국내에서 처음으로 보고하는 바이다. 또한 형은 칼만 증후군에서 동반되어 나타날 수 있는 오른쪽 신장 무형성증과 왼쪽 감각신경난청 소견을 보였지만 동생에서는 이러한 소견 없이 잠복고환의 소견만을 보임으로써 같은 유전자의 이상으로 인한 질환이지만 서로 다른 임상 양상을 보이는 것을 관찰하여 KAL1유전자의 발현에 다른 modifier gene 이나 epigenetic factor들이 작용함을 추정할 수 있었다.
Abstract
Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. Although the vast majority of KS cases are sporadic, some X-linked recessive (KAL1), autosomal dominant (FGFR1), and autosomal recessive (most commonly GNRHR) modes of inheritance have been described. Two boys were referred to our department because of cryptorchidism and the absence of puberty. Upon laboratory evaluation they were diagnosed with hypogonadotropic hypogonadism. Agenesis of the olfactory bulbs was detected in radiologic tests, and total deletion of the KAL1 gene was detected through multiplex ligation-dependent probe amplification (MLPA). Although cryptorchidism was diagnosed in the siblings, only the older brother suffered from sensorineural hearing loss and right renal agenesis, a feature that had been reported in X-linked KS. We describe herein the clinical heterogeneity of two affected brothers who carry a complete deletion in KAL1; this is the first case of familial Kallmann syndrome due to the complete deletion of the KAL1 gene reported in Korea.(J Korean Soc Pediatr Endocrinol 2011;16:61-65)
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