This diagnostic image displays two coronal T2-weighted brain MRI scans, labeled (A) and (B), focusing on the anterior cranial fossa of two different patients. In image A, red arrows specifically point to the olfactory region above the ethmoid bone's cribriform plate. Both images demonstrate bilateral dysplasia and hypoplasia of the olfactory bulbs, olfactory tracts, and the corresponding olfactory sulci. This anatomical area normally contains well-defined, rounded olfactory bulbs sitting within the olfactory sulci of the frontal lobes. However, in these patients, the sulci are shallow or poorly formed, and the olfactory structures are visibly diminished or absent. This radiological finding is a hallmark diagnostic feature of Kallmann syndrome, reflecting a failure in the development and migration of the olfactory nerves and gonadotropin-releasing hormone (GnRH) neurons. The images illustrate the neuroanatomical basis for clinical anosmia or hyposmia in the context of idiopathic hypogonadotropic hypogonadism.

This diagnostic image set displays whole-mount in situ hybridization (WISH) of Danio rerio (zebrafish) embryos at 56 hours post-fertilization (hpf), used as a disease model for Kallmann syndrome (KS). The panels compare gene expression patterns between 'cars2 morphants' (knockdown group) and control embryos across four genetic markers: gnrh3, gnrh2, kal1a, and kal1b. In the gnrh3 panels (a, a', b, b'), red arrows highlight the ectopic migration of GnRH3 neurons in the cars2 morphants compared to the restricted, normal distribution in the control embryos. Conversely, the expression patterns for gnrh2 (c, d), kal1a (e, f), and kal1b (g, h) appear consistent between the morphant and control groups. These images demonstrate the specific role of the mitochondrial cysteinyl-tRNA synthetase (CARS2) in the developmental migration of GnRH neurons, a key pathophysiology in human hypogonadotropic hypogonadism. The visual evidence supports the educational concept of gene-environment or synergistic genetic interactions in neurodevelopmental migration disorders.

This set of fluorescence microscopy images illustrates the development of the GnRH3 neuron fiber network in zebrafish embryos (tg(gnrh3:EGFP)) at 48 hours post-fertilization (hpf) and 72 hpf across different genotypes. Panels A and E show wild-type (WT) embryos with highly organized fiber distribution throughout the olfactory bulbs (OB), optic chiasm (OC), and anterior commissure (AC). Panels B and F demonstrate that prokr1b heterozygous mutants retain a similar organized architecture. In contrast, prokr1b homozygous mutants (Panels C and G) exhibit significant axon misrouting and disorganization, particularly at the rostral region and the optic chiasm. Panels D and H demonstrate a successful phenotypic rescue in homozygous mutants following the injection of wild-type prokr1b mRNA, restoring the structural integrity of the GnRH3 network. This comparative visualization highlights the critical role of the prokr1b gene in guiding the migration and pathfinding of GnRH neurons, which is medically relevant for understanding the molecular basis of Kallmann syndrome and related hypogonadotropic hypogonadism disorders.

Two coronal magnetic resonance imaging (MRI) scans of the brain (labeled a and b) focusing on the anterior cranial fossa and olfactory region. The images demonstrate aplasia of the olfactory bulbs and tracts, a hallmark radiological finding in Kallmann syndrome. Image (a) shows the inferior frontal lobes with altered signal intensity and a lack of distinct olfactory bulb morphology within the olfactory sulci. Image (b) further confirms the bilateral absence of these structures. The nasal cavities and ethmoid sinus regions are visible inferiorly with normal aeration (dark signal). The imaging demonstrates the key diagnostic feature for patients presenting with congenital hypogonadotropic hypogonadism and anosmia/hyposmia. This comparison illustrates the developmental abnormalities of the olfactory system associated with genetic neuroendocrine disorders.