Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism.

Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin-releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0.3 nmol/L) and undetectable gonadotropins (luteinizing hormone and follicle-stimulating hormone both <0.5 U/L), suggestive of CHH. Genetic testing identified a de novo, heterozygous mutation in fibroblast growth factor receptor 1 (FGFR1 p.L630P). L630 resides on the ATP binding cleft of the FGFR1 tyrosine kinase domain, and L630P is predicted to cause a complete loss of receptor function. Cell-based assays confirmed that L630P abolishes FGF8 signaling activity. Identification of a loss-of-function de novo FGFR1 mutation in this patient confirms the diagnosis of CHH, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of CHH in childhood.

MRI cisternography, and the localization of CSF fistulae.

Accurate localization of CSF fistulae not only makes the planning of surgery easier, but it also increases the chances of successful dural repair and eliminates negative exploration. CSF fistulae localization has been a problem for many years, and several methods have been used to pin-point the site of CSF leakage with variable degree of success. Recently, contrast CT cisternography (CCTC) has replaced radio-isotope cisternography (RIC) in many centres. However, both methods are invasive, time consuming, contraindicated in patients with intracranial mass lesions and insensitive in detecting inactive CSF leaks. Furthermore, in both, ionizing radiation is used and both techniques may lead to allergic reactions or seizures. On the other hand, T2-weighted Magnetic Resonance Imaging (MRI) shows the CSF as a high signal without the need to inject contrast media intrathecally. Furthermore, MRI demonstrates the intracranial anatomy and pathology in detail in multiple planes within a relatively short time. MRI does not involve ionizing radiation and therefore is safely repeatable. MRI using T2-weighted sequences should be an ideal tool to locate precisely the site of CSF fistulae. This paper describes our experience with MRI cisternography in CSF fistulae localization. Eleven patients with inactive CSF fistulae were investigated. MRI cisternography localized the site of fistula in each case. All patients were explored surgically and the site of CSF fistula was confirmed and repaired intradurally with a pericranial graft and fibrin glue without recurrence or meningitis.