The Clinical and Genotypic Spectrum of Scoliosis in Multiple Pterygium Syndrome: A Case Series on 12 Children

Abstract

Background: Multiple pterygium syndrome (MPS) is a genetically heterogeneous rare form of arthrogryposis multiplex congenita characterized by joint contractures and webbing or pterygia, as well as distinctive facial features related to diminished fetal movement. It is divided into prenatally lethal (LMPS, MIM253290) and nonlethal (Escobar variant MPS, MIM 265000) types. Developmental spine deformities are common, may present early and progress rapidly, requiring regular fo llow-up and orthopedic management. Methods: Retrospective chart review and prospective data collection were conducted at three hospital centers. Molecular diagnosis was confirmed with whole exome or whole genome sequencing. Results: This case series describes the clinical features and scoliosis treatment on 12 patients from 11 unrelated families. A molecular diagnosis was confirmed in seven; two with MYH3 variants and five with CHRNG. Scoliosis was present in all but our youngest patient. The remaining 11 patients spanned the spectrum between mild (curve ≤ 25°) and malignant scoliosis (≥50° curve before 4 years of age); the two patients with MYH3 mutations presented with malignant scoliosis. Bracing and serial spine casting appear to be beneficial for a few years; non-fusion spinal instrumentation may be needed to modulate more severe curves during growth and spontaneous spine fusions may occur in those cases. Conclusions: Molecular diagnosis and careful monitoring of the spine is needed in children with MPS.

Combining Gene Mutation with Expression of Candidate Genes to Improve Diagnosis of Escobar Syndrome

“…In the literature, five patients were described with a heterozygous compound mutation causing Escobar syndrome [ 13 , 15 ]. Other studies suggested the presence of variants in the regulatory intronic regions in Escobar patients given their absence in exons and other genes associated with this pathology, such as CHRNA1 , CHRND, TPM2, and MYH3 [ 4 , 38 , 39 ]. Other studies, could not associate the phenotype with any particular related genetic variant…”

Functional assessment of a novel biallelic MYH3 variation causing CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B)

“…Patients with this disorder often exhibit significant scoliosis and limited mobility. To date, only six studies with less than 20 patients involving with CPSF1B have been reported (Cameron‐Christie et al., 2018 ; Dahan‐Oliel et al., 2021 ; Hakonen et al., 2020 ; Kamien et al., 2022 ; Thiffault et al., 2019 ; Zhao et al., 2022 ), which keeps the characteristic spectrum, natural clinical course, and pathogenesis of this disease still far from well‐known.…”

Overview of Gene Special Issue “Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis”

“…Further research using genomics and animal models to identify prognostic factors and therapeutic targets for AMC needs to be implemented. Dahan et al [ 10 ] described the clinical and genetic heterogeneity in patients with multiple pterygium syndrome and scoliosis, harboring mutations in CHNRG and MYH3 .…”