Department of Pediatrics, School of Medicine, Democritus University of Thrace, Alexandroupolis, Thrace, Greece.
Handb Clin Neurol. 2021;181:9-27. doi: 10.1016/B978-0-12-820683-6.00002-6.
Pituitary stalk interruption syndrome (PSIS) is a distinct developmental defect of the pituitary gland identified by magnetic resonance imaging and characterized by a thin, interrupted, attenuated or absent pituitary stalk, hypoplasia or aplasia of the adenohypophysis, and an ectopic posterior pituitary. The precise etiology of PSIS still remains elusive or incompletely confirmed in most cases. Adverse perinatal events, including breech delivery and hypoxia, were initially proposed as the underlying mechanism affecting the hypothalamic-pituitary axis. Nevertheless, recent findings have uncovered a wide variety of PSIS-associated molecular defects in genes involved in pituitary development, holoprosencephaly (HPE), neural development, and other important cellular processes such as cilia function. The application of whole exome sequencing (WES) in relatively large cohorts has identified an expanded pool of potential candidate genes, mostly related to the Wnt, Notch, and sonic hedgehog signaling pathways that regulate pituitary growth and development during embryogenesis. Importantly, WES has revealed coexisting pathogenic variants in a significant number of patients; therefore, pointing to a multigenic origin and inheritance pattern of PSIS. The disorder is characterized by inter- and intrafamilial variability and incomplete or variable penetrance. Overall, PSIS is currently viewed as a mild form of an expanded HPE spectrum. The wide and complex clinical manifestations include evolving pituitary hormone deficiencies (with variable timing of onset and progression) and extrapituitary malformations. Severe and life-threatening symptomatology is observed in a subset of patients with complete pituitary hormone deficiency during the neonatal period. Nevertheless, most patients are referred later in childhood for growth retardation. Prompt and appropriate hormone substitution therapy constitutes the cornerstone of treatment. Further studies are needed to uncover the etiopathogenesis of PSIS.
垂体柄中断综合征（PSIS）是一种通过磁共振成像识别的独特的垂体发育缺陷，其特征是垂体柄变薄、中断、衰减或缺失，腺垂体发育不良或发育不全，以及异位的后垂体。在大多数情况下，PSIS 的精确病因仍然难以捉摸或不完全确定。最初提出不良围产期事件，包括臀位分娩和缺氧，是影响下丘脑-垂体轴的潜在机制。然而，最近的发现揭示了与 PSIS 相关的各种分子缺陷，这些缺陷涉及参与垂体发育、全前脑（HPE）、神经发育和其他重要细胞过程（如纤毛功能）的基因。全外显子组测序（WES）在相对较大的队列中的应用已经确定了一个扩展的潜在候选基因池，这些基因主要与调节胚胎发生期间垂体生长和发育的 Wnt、Notch 和 sonic hedgehog 信号通路有关。重要的是，WES 在相当数量的患者中揭示了共存的致病性变异体；因此，指出了 PSIS 的多基因起源和遗传模式。该疾病的特征是个体内和个体间的变异性以及不完全或可变的外显率。总体而言，PSIS 目前被视为扩展的 HPE 谱的一种轻度形式。广泛而复杂的临床表现包括不断发展的垂体激素缺乏症（具有不同的发病时间和进展）和垂体外畸形。在新生儿期完全缺乏垂体激素的亚组患者中观察到严重和危及生命的症状。然而，大多数患者在儿童后期因生长迟缓而就诊。及时和适当的激素替代治疗是治疗的基石。需要进一步的研究来揭示 PSIS 的病因发病机制。
