GH treatment in pediatric Down syndrome: a systematic review and mini meta-analysis

Shaki, David; Hershkovitz, Eli; Tamam, Shai; Bollotin, Arkadi; David, Odeya; Yalovitsky, Guy; Loewenthal, Neta; Carmon, Lior; Walker, Dganit; Nowak, Raphaël; Haim, Alon

doi:10.3389/fendo.2023.1135768

Cited by 2 publications

(1 citation statement)

References 34 publications

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“…Intellectual disability (IQ < 70) is uncommon in NS patients [1], whereas it is much more frequent in other rasopathies such as CFCS or CS [24,25]. As treatment with rhGH in patients with intellectual disability raises ethical questions [26], this manifestation should be taken into consideration in this setting.…”

Section: Discussionmentioning

confidence: 99%

Genotypic Findings in Noonan and Non-Noonan RASopathies and Patient Eligibility for Growth Hormone Treatment

Carcavilla,

Cambra,

Santomé

et al. 2023

JCM

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Molecular study has become an invaluable tool in the field of RASopathies. Treatment with recombinant human growth hormone is approved in Noonan syndrome but not in the other RASopathies. The aim of this study was to learn about the molecular base of a large cohort of patients with RASopathies, with particular emphasis on patients with pathogenic variants in genes other than PTPN11, and its potential impact on rGH treatment indication. We reviewed the clinical diagnosis and molecular findings in 451 patients with a genetically confirmed RASopathy. HRAS alterations were detected in only 2 out of 19 patients referred with a Costello syndrome suspicion, whereas pathogenic variants in RAF1 and SHOC2 were detected in 3 and 2, respectively. In 22 patients referred with a generic suspicion of RASopathy, including cardiofaciocutaneous syndrome, pathogenic alterations in classic Noonan syndrome genes (PTPN11, SOS1, RAF1, LZTR1, and RIT1) were found in 7 patients and pathogenic variants in genes associated with other RASopathies (HRAS, SHOC2, and PPPCB1) in 4. The correct nosological classification of patients with RASopathies is critical to decide whether they are candidates for treatment with rhGH. Our data illustrate the complexity of differential diagnosis in RASopathies, as well as the importance of genetic testing to guide the diagnostic orientation in these patients.

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Section: Discussionmentioning

confidence: 99%

Genotypic Findings in Noonan and Non-Noonan RASopathies and Patient Eligibility for Growth Hormone Treatment

Carcavilla,

Cambra,

Santomé

et al. 2023

JCM

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show abstract

Genotype–Phenotype Correlation of GNAS Gene: Review and Disease Management of a Hotspot Mutation

Cipriano,

Ferrigno,

Andolfo

et al. 2024

IJMS

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Defects of the GNAS gene have been mainly associated with pseudohypoparathyroidism Ia. To date, pathogenic missense, frameshift, non-sense and splicing variants have been described in all the 13 exons of the GNAS gene. Of them, a specific mutation, namely the 4 bp deletion c.565_568delGACT, is currently considered a mutation hotspot. Recent articles performed genotype–phenotype correlations in patients with GNAS-related pseudohypoparathyroidism Ia (PHP1a) but a specific focus on this hotspot is still lacking. We reported two cases, from our department, of PHP1a associated with c.565_568delGACT deletion and performed a literature review of all the previously reported cases of the 4 bp deletion hotspot. We found a higher prevalence of brachydactyly, round face, intellectual disability and subcutaneous/heterotopic ossifications in patients with the c.565_568delGACT as compared to the other variants in the GNAS gene. The present study highlights the different prevalence of some clinical features in patients with the c.565_568delGACT variant in the GNAS gene, suggesting the possibility of a personalized diagnostic follow-up and surveillance for these patients.

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GH treatment in pediatric Down syndrome: a systematic review and mini meta-analysis

Cited by 2 publications

References 34 publications

Genotypic Findings in Noonan and Non-Noonan RASopathies and Patient Eligibility for Growth Hormone Treatment

Genotypic Findings in Noonan and Non-Noonan RASopathies and Patient Eligibility for Growth Hormone Treatment

Genotype–Phenotype Correlation of GNAS Gene: Review and Disease Management of a Hotspot Mutation

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