Gene Dx, KAL1 in Kallmann Syndrome

Collect at NMCP only Mon-Thursday by 1200

906

KAL1 Del/Dup

2-5 mL Blood - Lavender Top Tube

Ship overnight at ambient temperature, using a cool pack in hot weather. Specimens may be refrigerated for 7 days prior to shipping.

Ambient

3-4 weeks

Kallmann syndrome (KS) is usually characterized by hypogonadotropic hypogonadism and anosmia. Hearing loss, synkinesia, cleft lip/palate, and other anomalies are also observed in some patients. A defective sense of smell, either partial (hyposmia) or complete (anosmia), distinguishes KS from normosmic idiopathic hypogonadotropic hypogonadism (IHH), which can be associated with mutations in the GnRHR and GPR54 genes. Due to hypothalamic GnRH deficiency, males with KS demonstrate cryptorchidism, testicular atrophy, and microphallus at birth and subsequent failure to undergo normal puberty during adolescence. Up to 30% of males also exhibit renal agenesis. Females with KS usually present with primary amenorrhea but can also exhibit hyposmia, synkinesia, and other anomalies. Mutations in at least two genes have been shown to cause KS. Mutations in the X-linked KAL1 gene result in the classic genital and olfactory features of Kallmann syndrome. This is known as Type 1 Kallmann syndrome and arises from abnormal anosmin-1 protein production. Type 2 Kallmann syndrome is caused by mutations in the autosomal FGFR1 gene. This gene is also involved in craniosynostosis disorders, including Pfeiffer syndrome, trigonocephaly, and osteoglophonic dysplasia. Inactivating mutations in FGFR1 causes Type 2 KS whereas gain-of-function or activating mutations are associated with craniosynostosis. Although craniosynostosis is not observed in Kallmann syndrome, orofacial clefting and hypodontia can be seen in some Type II KS patients. Both Type I and II KS phenotypes show clinical variability and reduced penetrance, particularly in FGFR1-associated KS. Overall, about 25% of Kallmann syndrome cases are due to mutation in KAL1 (5-10%) or FGFR1 (8-16%).