Corrections of Lower Limb Deformities in Patients with Diastrophic Dysplasia

Kaissi, Ali Al; Kenis, Vladimir; Melchenko, Evgeniy; Chehida, Farid Ben; Rudolf, G.; Klaushofer, Klaus; Grill, Franz

doi:10.1111/os.12146

Cited by 13 publications

(7 citation statements)

References 17 publications

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“…Genotype and phenotype of patient DISCO-JST8 strongly suggest the diagnosis of diastrophic dysplasia (DTD), although we are unable to determine whether the variants occur in trans or in cis because of the unavailability of the mother’s sample. Typical features of DTD include limb shortening, normal-sized skull, hitchhiker thumbs, and spinal deformities, 13 whereas language retardation and testicle hypoplasia are not associated with DTD.…”

Section: Resultsmentioning

confidence: 99%

Deciphering the mutational signature of congenital limb malformations

Sun

Huang

Zhao

et al. 2021

Molecular Therapy - Nucleic Acids

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Congenital limb malformations (CLMs) affect 1 in 500 live births. However, the value of exome sequencing (ES) for CLM is lacking. The purpose of this study was to decipher the mutational signature of CLM on an exome level. We enrolled a cohort of 66 unrelated probands (including 47 families) with CLM requiring surgical correction. ES was performed for all patients and available parental samples. A definite molecular diagnosis was achieved in 21 out of 66 (32%) patients. We identified 19 pathogenic or likely pathogenic single-nucleotide variants and three copy number variants, of which 11 variants were novel. We identified four variants of uncertain significance. Additionally, we identified RPL9 and UBA2 as novel candidate genes for CLM. By comparing the detailed phenotypic features, we expand the phenotypic spectrum of diastrophic dysplasia and chromosome 6q terminal deletion syndrome. We also found that the diagnostic rate was significantly higher in patients with a family history of CLM (p = 0.012) or more than one limb affected (p = 0.034). Our study expands our understanding of the mutational and phenotypic spectrum of CLM and provides novel insights into the genetic basis of these syndromes.

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Section: Resultsmentioning

confidence: 99%

Deciphering the mutational signature of congenital limb malformations

Sun

Huang

Zhao

et al. 2021

Molecular Therapy - Nucleic Acids

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“…The current approach in the general management of patients with SLS26A2-related skeletal dysplasias, including orthopedic surgery for children with major musculoskeletal involvement, remains empirical and does not account genetic variants [ 28 ]. The detailed knowledge of clinical and genetic correlations can influence this approach.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characteristics of Multiple Epiphyseal Dysplasia Type 4

Маркова

Kenis

Melchenko

et al. 2022

Genes

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Multiple epiphyseal dysplasias (MED) are a clinically and genetically heterogeneous group of skeletal dysplasias with a predominant lesion in the epiphyses of tubular bones. Variants in the SLC26A2 gene cause their autosomal recessive form (rMED or MED type 4). The accumulation of data regarding the genotype–phenotype correlation can help in the diagnosis and proper management of these patients. The aim of this study was to survey the clinical and genetic characteristics of 55 patients with MED type 4 caused by variants in the SLC26A2 gene. Diagnosis confirmation was carried out by radiography and custom panel sequencing consisting of 166 genes responsible for the development of hereditary skeletal pathology. This was followed by the validation of the identified variants using automated Sanger sequencing (for six patients) and the direct automatic Sanger sequencing of the coding sequence and the adjacent intron regions of the SLC26A2 gene for 49 patients. Based on the clinical and genetic analysis of our sample of patients, two main MED type 4 phenotypes with early and late clinical manifestations were identified. An early and more severe form of the disease was observed in patients with the c.835C > T variant (p.Arg279Trp), and the late and milder form of the disease was observed in patients with the c.1957T > A variant (p.Cys653Ser) in the homozygous or compound heterozygous state with c.26 + 2T > C. It was also shown that only three pathogenic variants were found in 95.3% of the alleles of Russian patients with MED type 4: c.1957T > A (p.Cys653Ser), c.835C > T (p.Arg279Trp), and c.26 + 2T > C; thus, it can be assumed that the primary analysis of these variants will contribute to the optimal molecular genetic diagnostics of MED type 4.

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“…Cavovarus deformity which is often present is treated with the Ponseti method of casting in patients in the age group <6 months. There is a need for soft-tissue release in patients with after the walking age and in resistant cases, it may need aggressive release [ 6 ]. Metatarsus adductus deformity if resistant may need bony procedures and various ostetomies have been described [ 7 , 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Association and Role of Surgery for the Treatment of Lower Limb Deformities in Diastrophic Dysplasia: A Case Report

Tripathi¹,

Choudhary²,

Singh³

et al. 2021

JOCR

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Introduction: Diastrophic dysplasia (DTD) results from SCN26A2 gene mutation, with autosomal recessive inheritance and widely variable phenotype. The gene has been mapped to chromosome 5q32-q33.1. Case Report: We present a case of a 4-year-old female with short stature, bilateral feet and knee deformity, and dysplastic facies. SCN26A2 mutations were seen in patient as well as parents. She underwent multiple orthopedic procedures involving metatarsals, gastrosoleus, and distal femur. Based on typical clinical features, DTD was suspected. Genetic studies of patient and parents provided the exact diagnosis in this case. Conclusion: Genetic diagnosis and family counseling are important caveat of management. Key features like ear abnormalities help to suspect diagnosis which requires a high index of suspicion. Associated bony and soft-tissue abnormalities of lower limb may require surgical intervention for improvement of gait, functions, and cosmesis. Keywords: Diastrophic dysplasia, Skeletal dysplasia, Ear abnormalities, SCN26A2, Osteotomy.

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Corrections of Lower Limb Deformities in Patients with Diastrophic Dysplasia

Abstract: Arthrogryposis multiplex is the usual terminology used to describe the abnormality in infants with multiple contractures. Diligent orthopaedic care should be provided based on an accurate understanding of the associated syndromes in such children.

Cited by 13 publications

References 17 publications

Deciphering the mutational signature of congenital limb malformations

Deciphering the mutational signature of congenital limb malformations

Clinical and Genetic Characteristics of Multiple Epiphyseal Dysplasia Type 4

Genetic Association and Role of Surgery for the Treatment of Lower Limb Deformities in Diastrophic Dysplasia: A Case Report

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