Chiari I malformation in patients with RASopathies

Han, Yong Hwan; Chen, Min; Wang, Hangzhou

doi:10.1007/s00381-020-05034-2

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…The RAS/MAPK pathway is involved in the control of processes of embryonic and postnatal development, such as cell specification and axon growth, and also in the control of adult plasticity of the central and peripheral nervous systems [14,15]. Consequently, genetic mutations associated with RASopathies give rise to multiple neurological impairments [9]: (i) structural intracranial anomalies like Chiari I malformation [16], syringomyelia, cerebral vascular anomalies, benign external hydrocephalus, craniosynostosis and posterior fossa anomalies [17]; (ii) neuropathies or headaches; (iii) seizures [18]; and (iv) diverse cognitive deficits, such as psychomotor delay [19] and cognitive abnormalities [20]. As in other neurodevelopmental disorders, these cognitive deficits consist in language delays [21], deficits in learning ability and memory [20], and social impairments that are partly reminiscent of autism spectrum disorders [22].…”

Section: Neurological Manifestations Of Rasopathiesmentioning

confidence: 99%

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

Rodríguez-Martín,

Báez-Flores,

Ribes

et al. 2024

Biomedicines

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RASopathies, a group of neurodevelopmental congenital disorders stemming from mutations in the RAS/MAPK pathway, present a unique opportunity to delve into the intricacies of complex neurological disorders. Afflicting approximately one in a thousand newborns, RASopathies manifest as abnormalities across multiple organ systems, with a pronounced impact on the central and peripheral nervous system. In the pursuit of understanding RASopathies’ neurobiology and establishing phenotype–genotype relationships, in vivo non-mammalian models have emerged as indispensable tools. Species such as Danio rerio, Drosophila melanogaster, Caenorhabditis elegans, Xenopus species and Gallus gallus embryos have proven to be invaluable in shedding light on the intricate pathways implicated in RASopathies. Despite some inherent weaknesses, these genetic models offer distinct advantages over traditional rodent models, providing a holistic perspective on complex genetics, multi-organ involvement, and the interplay among various pathway components, offering insights into the pathophysiological aspects of mutations-driven symptoms. This review underscores the value of investigating the genetic basis of RASopathies for unraveling the underlying mechanisms contributing to broader neurological complexities. It also emphasizes the pivotal role of non-mammalian models in serving as a crucial preliminary step for the development of innovative therapeutic strategies.

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Section: Neurological Manifestations Of Rasopathiesmentioning

confidence: 99%

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

Rodríguez-Martín,

Báez-Flores,

Ribes

et al. 2024

Biomedicines

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“…Arnold-Chiari malformation is commonly seen in RASopathies, and several cases have been reported in the medical literature in NS patients although the incidence is not known ( 28 , 173 ). Arnold-Chiari is also observed in other medical conditions, including GHD (5–20%) ( 174 ), due to the underdevelopment of certain cranial bone structures.…”

Section: Overview Of Cautions and Side Effects During Rhgh Treatmentmentioning

confidence: 99%

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Stagi

Ferrari

et al. 2022

Front. Endocrinol.

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Noonan syndrome (NS) is a disorder characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature. NS is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway, and it is typically associated with substantial genetic and clinical complexity and variability. Short stature is a cardinal feature in NS, with evidence indicating that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulin-like growth factor I (IGF-1) are contributing events for growth failure in these patients. Decreased IGF-I, together with low/normal responses to GH pharmacological provocation tests, indicating a variable presence of GH deficiency/resistance, in particular in subjects with pathogenic PTPN11 variants, are frequently reported. Nonetheless, short- and long-term studies have demonstrated a consistent and significant increase in height velocity (HV) in NS children and adolescents treated with recombinant human GH (rhGH). While the overall experience with rhGH treatment in NS patients with short stature is reassuring, it is difficult to systematically compare published data due to heterogeneous protocols, potential enrolment bias, the small size of cohorts in many studies, different cohort selection criteria and varying durations of therapy. Furthermore, in most studies, the genetic information is lacking. NS is associated with a higher risk of benign and malignant proliferative disorders and hypertrophic cardiomyopathy, and rhGH treatment may further increase risk in these patients, especially as dosages vary widely. Herein we provide an updated review of aspects related to growth, altered function of the GH/IGF axis and cell response to GH/IGF stimulation, rhGH treatment and its possible adverse events. Given the clinical variability and genetic heterogeneity of NS, treatment with rhGH should be personalized and a conservative approach with judicious surveillance is recommended. Depending on the genotype, an individualized follow-up and close monitoring during rhGH treatments, also focusing on screening for neoplasms, should be considered.

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“…J Clin Images Med Case Rep. 2021; 2(5): 1334. also rare in the literature. The first case was reported in 1982 [8], and only six additional cases have been reported since 2001 [9][10][11][12][13][14]. While an exact pathogenic link between the two syndromes remains to be fully understood, a retrospective cohort study found that approximately one-quarter of children with CIM harbor a RAS/MAPK-related mutation [15].…”

Section: Introductionmentioning

confidence: 99%

Chiari I malformation and Noonan’s syndrome: Shared manifestations of RASopathy

Still¹,

Miller²,

Dodd³

et al. 2021

J Clin Images Med Case Rep

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Neurologic sequalae of Noonan syndrome have been postulated in the literature. A topic of significance is the role of RASopathy in the shared pathophysiology of Noonan Syndrome and Chiari I malformation. In this unique case report, we present a patient with concomitant Noonan Syndrome and Chiari I with 4th ventricular outflow obstruction. The case highlights the importance of close clinical suspicion in this patient population. We utilize the case to delve into intricacies of the known pathophysiology and encourage ongoing investigation. Keywords: Noonan syndrome; Chiari I malformation; RASopathy.

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Chiari I malformation in patients with RASopathies

Cited by 6 publications

References 23 publications

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Chiari I malformation and Noonan’s syndrome: Shared manifestations of RASopathy

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