Feeding Problems in Patients with Noonan Syndrome: A Narrative Review

Tiemens, Dagmar K.; Haaften, Leenke van; Leenders, Erika; Wegberg, Annemiek M. J. van; Moor, Bregtje Gunther; Geelen, Joyce; Draaisma, J. M. T.

doi:10.3390/jcm11030754

Cited by 11 publications

(10 citation statements)

References 41 publications

(62 reference statements)

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“…Leoni et al (2016) observed an increased resting energy expenditure in individuals with CS, making a further step in the comprehension of the causes of growth failure, besides already reported the feeding difficulties, in individuals with RASopathies. This finding has also been reported in a patient with NS due to SHOC2 variant (Tiemens, van Haaften, et al, 2022).…”

Section: Growth Delay and Nutritional Aspectssupporting

confidence: 85%

“…Moreover, GERD should be promptly managed since it is one important contributing factor to the failure to thrive and may also develop into ARFID (DSM-V classification) (Tiemens, van Haaften, et al, 2022;Tiemens, Wegberg, Druten, & Draaisma, 2022) (Romano et al, 2017). A standard polymeric formula (1 kcal/ml) is usually preferred; before 12 months of age specific infants' formulas should be chosen (Pencharz, 2010).…”

Section: Management Of Feeding and Nutritional Issuementioning

confidence: 99%

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Management of nutritional and gastrointestinal issues in RASopathies: A narrative review

Onesimo

Giorgio

Viscogliosi

et al. 2022

American J of Med Genetics Pt C

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Noonan, Costello, and cardio-facio-cutaneous syndrome are neurodevelopmental disorders belonging to the RASopathies, a group of syndromes caused by alterations in the RAS/MAPK pathway. They are characterized by similar clinical features, among which feeding difficulties, growth delay, and gastro-intestinal disorders are frequent, causing pain and discomfort in patients. Hereby, we describe the main nutritional and gastrointestinal issues reported in individuals with RASopathies, specifically in Noonan syndrome, Noonan syndrome-related disorders, Costello, and cardio-faciocutaneous syndromes. Fifty percent of children with Noonan syndrome may experience feeding difficulties that usually have a spontaneous resolution by the second year of life, especially associated to genes different than PTPN11 and SOS1. More severe manifestations often require artificial enteral nutrition in infancy are observed in Costello syndrome, mostly associated to c.34G>A substitution in the HRAS gene.In cardio-facio-cutaneous syndrome feeding issues are usually present (90-100% of cases), especially in individuals carrying variants in BRAF, MAP2K1, and MAP2K2 genes, and artificial enteral intervention, even after scholar age, may be required.Moreover, disorders associated with gastrointestinal dysmotility as gastroesophageal reflux and constipation are commonly reported in all the abovementioned syndromes. Given the impact on growth and on the quality of life of these patients, early evaluation and prompt personalized management plans are fundamental.

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Section: Growth Delay and Nutritional Aspectssupporting

confidence: 85%

Section: Management Of Feeding and Nutritional Issuementioning

confidence: 99%

Management of nutritional and gastrointestinal issues in RASopathies: A narrative review

Onesimo

Giorgio

Viscogliosi

et al. 2022

American J of Med Genetics Pt C

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“…Feeding difficulties and consecutive failure to thrive in infancy and early childhood occur with high frequency and variable severity (Leoni, Giorgio, et al, 2022; Tiemens et al, 2022). Gastrointestinal dysmotility has been suggested as a cause, but the problem is probably complex.…”

Section: Shared Patterns Of Organ Involvement In Ns‐like Rasopathiesmentioning

confidence: 99%

Clinical overview on RASopathies

Zenker

2022

American J of Med Genetics Pt C

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RASopathies comprise a group of clinically overlapping developmental disorders caused by genetic variations affecting components or modulators of the RAS-MAPK signaling cascade, which lead to dysregulation of signal flow through this pathway. Noonan syndrome and the less frequent, clinically related disorders, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, and Noonan syndrome-like disorder with loose anagen hair are part of the RASopathy spectrum and share a recognizable pattern of multisystem involvement. This review describes the "Noonan syndrome-like" phenotype as a common phenotypic signature of generalized developmental RAS pathway dysregulation. Distinctive features of the different entities are revisited against the background of the understanding of underlying genetic alterations and genotype correlations, which has evolved rapidly during the past 20 years, thereby leading to suggestions regarding the nosology of RASopathies. K E Y W O R D S cardiofaciocutaneous syndrome, Costello syndrome, LEOPARD syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome-like disorder with loose anagen hair 1 | INTRODUCTION The term "RASopathies" was coined in 2009 (Tidyman & Rauen, 2009). It denotes a group of clinically overlapping multisystem disorders that share a common molecular pathogenesis in that the underlying genetic variations affect components or modulators of the RAS-MAPK signaling cascade and lead to dysregulation of signal flow through this pathway. No generally accepted definition and definitive delineation of RASopathies exist, so far. The major classes of disorders that have been grouped under this umbrella term are summarized in Table 1. This clinical overview is focused on Noonan syndrome (NS; MIM #PS163950) and the less frequent, clinically related disorders, Costello syndrome (CS; MIM #218040), cardiofaciocutaneous syndrome (CFCS: MIM #PS115150), Noonan syndrome with multiple lentigines (NSML; MIM #151100), Noonan syndrome-like disorder with loose anagen hair (NSLH; MIM #PS607721), collectively referred to in the following as "Noonan syndrome-like RASopathies (NS-like RASopathies)." They represent disorders that are caused by a mild to moderate and generalized constitutional RAS pathway dysregulation (Figure 1a) and have a multisystem phenotype. Based on the current pathogenetic concepts and understanding it can be concluded that the "NS-like" clinical picture represents the common phenotypic signature of a systemic RAS pathway dysregulation that starts in the embryonic period. This notion is supported by the fact that all genes known to cause NS-like RASopathies encode for components or modulators of the RAS-MAPK signaling cascade. However, this does not mean that disturbed signaling through MAPKs as the sole effectors can explain all the organ-specific pathophysiology. In fact, cellular pathways are interconnected and abnormal signaling in one of them

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“…Feeding difficulties in NS subjects are extremely frequent ( 19 ) and may cause transient failure to thrive and poor weight gain during the neonatal period and infancy in 55 to 100% of cases, depending on the molecular subtype ( 20 , 41 ).…”

Section: Growth and Growth Hormone-igf-1 Axis In Noonan Syndromementioning

confidence: 99%

“…From an auxological point of view, NS is one of the most prevalent non-chromosomal disorders affecting development and growth ( 17 , 18 ). In affected subjects, birth weight and length are generally normal, although postnatal growth failure is observed ( 19 , 20 ). Commonly, height tends to follow the third centile from ages two to four years until puberty, when below-average height velocity and an attenuated pubertal growth spurt tend to occur with a near adult height in the lower limits of normal values ( 21 – 23 ).…”

Section: Introductionmentioning

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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Feeding Problems in Patients with Noonan Syndrome: A Narrative Review

Cited by 11 publications

References 41 publications

Management of nutritional and gastrointestinal issues in RASopathies: A narrative review

Management of nutritional and gastrointestinal issues in RASopathies: A narrative review

Clinical overview on RASopathies

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

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