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. 2021 Jan 22;16(1):43.
doi: 10.1186/s13023-021-01674-y.

Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status

Chiara Leoni  1 , Domenico Marco Romeo  2 , Michele Pelliccioni  3 , Mariangela Di Già  3 , Roberta Onesimo  3 , Valentina Giorgio  3 , Elisabetta Flex  4 , Marta Tedesco  3 , Marco Tartaglia  5 , Donato Rigante  3   6 , Antonio Valassina #  6   7 , Giuseppe Zampino #  3   6
Affiliations

Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status

Chiara Leoni et al. Orphanet J Rare Dis. .

Abstract

Background: Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due to their rarity, the characterization of the musculo-skeletal phenotype in both disorders has been poorly characterized.

Patients and methods: Herein we reported data on orthopedic findings and functional status of a large sample of CS and CFCS patients. Thirty-four patients (CS = 17 and CFCS = 17) were recruited. Functional and disability evaluations were performed by assessing the 6-min walking test (6MWT) and Pediatric Outcomes Data Collection Instrument (PODCI). Genotype/phenotype correlation was also provided.

Results: Orthopedic manifestations are highly prevalent in CS and CFCS and overlap in the two disorders. Overall, patients with CS harboring the recurrent HRAS Gly12Ser substitution show a more severe skeletal phenotype compared to patients carrying the Gly12Ala and Gly13Cys variants. Among CFCS patients, those with the MAP2K1/2 variant show different skeletal characteristics compared to BRAF variants, with a higher prevalence of orthopedic abnormalities. Functional assessment showed that patients with CS and CFCS reached lower values compared to the general population, with CFCS patients displaying the lowest scores.

Conclusions: Orthopedic manifestations appear universal features of CS and CFCS and they can evolve across patients' life. Longitudinal assessment of disability status by using 6MWT and PODCI could be useful to evaluate the functional impact of orthopedic manifestations on patients' outcome and help planning a tailored treatment of these comorbidities.

Keywords: Cardio-facio-cutaneous syndrome; Clinical biomarker; Costello syndrome; Functional and disability assessment; Genotype–phenotype correlation; Innovative biotechnologies; Musculo-skeletal profiling; Patient-centered care; Personalized medicine; Rasopathies; Tailored treatments.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Six minute walk test in CS and CFCS
Fig. 2
Fig. 2
PODCI scores in Children (population under 11 years of age)
Fig. 3
Fig. 3
PODCI scores in Adolescents and young adults (population over 11 years of age)
See this image and copyright information in PMC

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