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Genetic Syndromes of Hypothalamic Dysfunction

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The Human Hypothalamus

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

The hypothalamus, only 0.4% of total central nervous system volume, is well positioned for its role as a neuroendocrine control center to monitor and initiate signaling for physical growth and development, social interaction, and response to environmental challenges for survival. Mendelian Inheritance in Man human gene database search reveals 113 clinical synopses entries with hypothalamic dysfunction. Genetic syndromes of hypothalamic dysfunction can result from gene mutations or alterations leading to (1) lack of spatiotemporal required levels of gene transcription control factors resulting in lack of required developmental molecular events, (2) uncontrolled gene expression and growth of tumors, (3) uncontrolled or absent neuronal networks or neuronal degeneration resulting in aberrant behavior and memory loss, (4) aberrant or uncontrolled neuroendocrine signaling, (5) uncontrolled water/electrolyte homeostasis, (6) aberrant or uncontrolled appetite and energy utilization homeostasis, and (7) uncontrolled aging and shortened survival. Key roles for the hypothalamus are demonstrated in genetic syndromes: Pallister-Hall, hypothalamic hamartomas; familial neurohypophyseal diabetes insipidus; Prader-Willi, gene imprinting, dysfunctional physical and mental development, and obesity; Wolfram, dysfunctional cellular autophagy “housekeeping” with progressive neural degeneration; Bardet-Biedl, dysfunctional cell networking due to ciliopathy; and leptin/leptin receptor, dysfunctional appetite and energy homeostasis. Animal models and digital databases are rapidly adding to our understanding of hypothalamic function, dysfunction, and aging.

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Authors and Affiliations

  1. Health Sciences Division, Mississippi Academy of Sciences, Jackson, MS, USA

    George William Moll Jr

  2. UMMC Pediatrics & Pediatric Endocrinology, Jackson, MS, USA

    George William Moll Jr

  3. Department of Internal Medicine/Endocrinology, Diabetes and Metabolism, University of Mississippi Medical Center (UMMC), Jackson, MS, USA

    Vishnu Garla

  4. Mississippi Center for Clinical and Translational Research, Jackson, MS, USA

    Vishnu Garla

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  1. George William Moll Jr
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  1. Department of Endocrinology, Diabetes, Metabolism and Weight Management, Ochsner Medical Center, New Orleans, LA, USA

    Gabriel I. Uwaifo

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Moll, G.W., Garla, V. (2021). Genetic Syndromes of Hypothalamic Dysfunction. In: Uwaifo, G.I. (eds) The Human Hypothalamus. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-030-62187-2_14

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