SLC26A2-Associated Diastrophic Dysplasia and rMED—Clinical Features in Affected Finnish Children and Review of the Literature

Diastrophic dysplasia (DTD) is a rare osteochondrodysplasia characterized by short-limbed short stature and joint dysplasia. DTD is caused by mutations in SLC26A2 and is particularly common in the Finnish population. However, the disease incidence in Finland and clinical features in affected individuals have not been recently explored. This registry-based study aimed to investigate the current incidence of DTD in Finland, characterize the national cohort of pediatric subjects with DTD and review the disease-related literature. Subjects with SLC26A2-related skeletal dysplasia, born between 2000 and 2020, were identified from the Skeletal dysplasia registry and from hospital patient registry and their clinical and molecular data were reviewed. Fourteen subjects were identified. Twelve of them were phenotypically classified as DTD and two, as recessive multiple epiphyseal dysplasia (rMED). From the subjects with available genetic data, 75% (9/12) were homozygous for the Finnish founder mutation c.-26+2T>C. Two subjects with rMED phenotype were compound heterozygous for p.Arg279Trp and p.Thr512Lys variants. The variable phenotypes in our cohort highlight the wide spectrum of clinical features, ranging from a very severe form of DTD to milder forms of DTD and rMED. The incidence of DTD in Finland has significantly decreased over the past decades, most likely due to increased prenatal diagnostics.

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

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.

AB0990 SECONDARY SUBACUTE ARTHRITIS IN CHILDREN WITH DIASTROPHIC DYSPLASIA AND RMED

Background:Progressive osteoarthritis is common in skeletal dysplasias. In the most of these disorders progress is relatively slow and acute pain with severe disability secondary to osteoarthritis is rare during childhood. Diastrophic dysplasia and rMED are quite unique among other skeletal dysplasias for secondary subacute arthritis (SSA). Protracted course of SSA can mimic JIA.Objectives:To analyse incidence and features of SSA in group of patients with DD/rMED.Methods:We retrospectively analysed for SSA our series of 39 patients with DD/rMED. Clinical, radiological and laboratory data were collected. Clinical assessment included pain (VAS), ROM (range of motion) and postural/walking disturbances. Radiological type by Yasunaga classification, neck-shaft angle (NSA) and articulo-trochanteric distance (AT distance) were estimated. MRI data regarding cartilage damage, joint effusion and bone marrow condition were noticed. Biomarkers of inflammation and immune response (ANA, RF, vimentin antibodies) were assessed in blood samples.Results:We identified 17 patients with hip joint SSA among 39 patients with DD/rMED (43%). Bilateral involvement was identified in 13 children with asynchronous appearance in all cases (from 2 to 18 months before the symptoms on the other side). Trauma (including iatrogenic damage during physiotherapy) preceded SSA in 9 cases. Pain, limited range of motion, limping and antalgic posture throughout the day were noticed in all the cases. Duration of these symptoms was from 4 weeks to 9 months. Progressive phase (increasing symptoms) took from 2 weeks to 4 months. General laboratory data were normal or indicated moderate inflammatory response without any specific changes. Radiolodgical data shows predictive sighs like NSA<110o, AT distance <10mm, fair or poor congruency by Yasunaga classification. Also radiological data demonstrated progressive subluxation with narrowing of articular space, osteoporosis, subchondral cysts.MRI revealed pseudo-erosive damaged cartilage in contact area with joint effusion and bone marrow oedema. Total cartilage matrix also visualized like intermittent and multi-layered = erosive-like chondrolysis (defective articular hyaline cartilage) in 11 patients (65%).Management included bed rest or partial weight bearing. NSAID were prescribed for 2-4 weeks with following usage according to the symptoms. Physical therapy to maintain range of motion was provided. One patient was operated (containment surgery for subluxation). In follow-up (2-7 years) 12 patients were painless at the daily life. 4 patients had intermittent pain and one patient (operated) - daily moderate pain. Range of motion was restored in 11 patients. Those patients who underwent in-hospital rehabilitation immediately after appearing of the symptoms demonstrated better outcome.Conclusion:SSA is typical for DD/rMED and leads to remarkable disability. Early recognition and non-surgical management are important for recovery. The quick reversibility of the clinical picture arthritis against the background of a short course of NSAIDs and rehabilitation is a characterized of non-autoimmune secondary inflammatory process (SSA). SSA not requiresanti-rheumatic treatment in childrenwith DD/rMED.References:[1]Al Kaissi, A., Kenis, V., Melchenko, E., Chehida, F. B., Ganger, R., Klaushofer, K., & Grill, F. (2014). Corrections of lower limb deformities in patients with diastrophic dysplasia.Orthopaedic surgery,6(4), 274-279.[2]Baindurashvili A.G., Kenis V.M., Melchenko E.V., Grill F., Al-Kaissi A. Complex orthopaedic management of patients with skeletal dysplasias.Traumatology and Orthopedics of Russia. 2014;(1):44-50. doi.org/10.21823/2311-2905-2014-0-1-44-50Disclosure of Interests:None declared

Diastrophic Dysplasia and Related Conditions, and Dysplasias with Joint Dislocations

This chapter further discusses bone dysplasias and includes discussion on achondrogenesis (type IB), atelosteogenesis type 2, diastrophic dysplasia, multiple epiphyseal dysplasia (recessive type [rMED]), Desbuquois dysplasia, chondrodysplasia with joint dislocations (IMPAD1/gPAPP type), Catel-Manzke syndrome, chondrodysplasia with congenital joint dislocations (CHST3-type), temtamy preaxial brachydactyly syndrome (TPBS), B4GALT7 deficiency, B3GAT3 deficiency, XYLT1 deficiency, spondyloepimetaphyseal dysplasia with joint laxity Beighton type, spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type), pseudodiastrophic dysplasia, and Steel syndrome. Each discussion includes major radiographic features, major clinical findings, genetics, major differential diagnoses, and a bibliography.