Kallmann syndrome and mirror movements: White matter quantitative evaluation with magnetic resonance imaging.

Kallmann syndrome (KS), characterized by the association of hypogonadotropic hypogonadism and anosmia, may present many other phenotypic abnormalities, including neurologic features as involuntary movements, called mirror movements (MM). MM etiology probably involves a complex mechanism comprising corticospinal tract abnormal development associated with deficient contralateral motor cortex inhibitory system. In this study, in order to address previous hypotheses concerning MM etiology, we identified and quantified white matter (WM) alterations in 21 KS patients, comparing subjects with and without MM and 16 control subjects, using magnetization transfer ratio (MTR) and T2 relaxometry (R2). Magnetization transfer and T2 double-echo images were acquired in a 1.5 T system. MTR and R2 were calculated pixel by pixel to initially create individual maps, and then, group average maps, co-registered with MNI305 stereotaxic coordinate system. After analysis of selected regions of interest, we demonstrated areas with higher T2 relaxation time and lower MTR values in KS patients, with and without MM, differently involving corticospinal tract projection, frontal lobes and corpus callosum. Higher MTR was observed only in pyramidal decussation when compared in both groups of patients with controls. In conclusion, we demonstrated that patients with KS have altered WM areas, presenting in a different manner in patients with and without MM. These data suggest axonal loss or disorganization involving abnormal pyramidal tracts and other associative/connective areas, relating to the presence or absence of MM. We also found a different pattern of alteration in pyramidal decussation, which can represent the primary area of neuronal disarrangement.

Two cases of Kallmann syndrome associated with empty sella.

Kallmann syndrome (KS) is a developmental disease characterized by the association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We report an unusual presentation of two females with KS and empty sella. These females, aged at 20 and 29-year-old, presented primary amenorrhea with prepubertal estradiol and low gonadotropin levels. No other significant clinical signs were observed. Empty sella was observed on MRI in both cases. Sequencing of FGFR1 gene, recently implicated in autosomal form of KS, was performed and one splicing mutation (IVS14 + 1G > A) was identified in one patient.

Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review.

Kallmann syndrome (KS) describes the association of isolated hypogonadotropic hypogonadism with hypo/anosmia. A few KS patients may reverse hypogonadism after testosterone withdrawal, a variant known as reversible KS. Herein, we describe the first mutation in KAL1 in a patient with reversible KS and review the literature. The proband was first seen at 22 years complaining of anosmia and lack of puberty. His brother had puberty at 30 years and a maternal granduncle had anosmia and delayed puberty. On physical examination, he was P(2)G(1), testes were 3 ml and bone age was 14 years. During 20 years of irregular testosterone replacement, he developed secondary sexual characteristics and testicular enlargement. At the age of 41 years, after stopping testosterone replacement for 5 months, his testes were 15 ml, serum testosterone, LH, and FSH responses to GnRH were normal, and his wife was pregnant. The molecular study revealed a cytosine insertion in exon 2 of KAL1, generating a frameshift at codon 75 and a premature stop at codon 85. The expected gene product is a truncated peptide with 85 of the 680 [corrected] amino acids present in the wild-type protein. Fourteen cases of reversible KS have been described but the genotype was only studied in a single case showing a heterozygous fibroblast growth factor receptor type 1 (FGFR1) mutation. Considering the low prevalence of mutations in KAL1 or FGFR1 in KS, it is possible that these genotypes are more prevalent in reversible KS than in other KS patients, but additional studies are necessary to confirm this hypothesis.

[Magnetic resonance in the diagnosis of Kallmann's syndrome. Presentation of 2 cases and review of the literature]. / La resonancia magnética en el diagnóstico del síndrome de Kallmann. Presentación de dos casos y revisión de la literatura.

The case of two women with a clinical picture of Kallmann's syndrome is reported. Definitive diagnosis of aplasia and hypoplasia of the olfactory bulbs was obtained by magnetic resonance imaging. A discussions of the clinical data and diagnosis approach is given. A review of available literature is also discussed.

La resonancia magnética en el diagnóstico del síndrome de Kallmann. Presentación de dos casos y revisión de la literatura / Magnetic resonance in the diagnosis of Kallmann's syndrome. Presentation of two cases and literature review

Se presentan los casos de dos mujeres con hipogonadismo hipogonadotrópico y trastornos olfatorios. El diagnóstico de síndrome de Kallmann fue corroborado en ambos casos con imágenes de Resonancia Magnética que mostraron aplasia de los bulbos olfatorios en un caso, e hipoplasia en el otro. Se destaca la función de la Resonancia Magnética para la demostración inequívoca por imagen del defecto olfatorio. Se comenta la presencia clínica y se hace una revisión de la literatura