Spondyloepiphyseal Dysplasia Research Articles

Congenital hypothyroidism mimicking spondyloepiphyseal dysplasia

Congenital hypothyroidism mimicking spondyloepiphyseal dysplasia

Guided growth surgery for angular deformity of the knee: one centres experience.

Angular deformity in the lower extremity can result in pain, gait disturbance, cosmetic deformity and joint degeneration. Up until the introduction of guided growth, which has since become the widely accepted treatment for frontal plane angular angular deformity around the knee in skeletally immature patients, treatment consisted of staples, corrective osteotomy or an angular epiphysiodesis. Guided growth modulation uses the tension band principle with the goal of treatment being to normalise the lower limb mechanical axis resulting in lower morbidity than previous treatments. In order to assess the success of this procedure we reviewed our results in an attempt to identify patients who may not benefit from this elegant procedure. We performed a retrospective review of prospectively collected surgical records and diagnostic imaging in our paediatric tertiary national referral centre to identify all patients who had guided growth surgery for coronal plane angular deformity of the knee from 2007 to 2023. We noted the patient demographics, diagnosis, peri-operative experience and outcome. All patients were followed until skeletal maturity, until their hardware was removed or at least 2years. Two hundred thirty-six patients were assessed for eligibility. Of the 282 treated knees which met the criteria for final assessment 55 (19.5%) were unsuccessful. Complications were few but included infection and metal-work prominence. Procedures that were less likely to be successfully included growth disturbances following trauma (18.8% failure) or infection (40%), tumour (66.6%), mucopolysaccharidoses type I (15.7%), spondyloepiphyseal dysplasia (25%) or Blount's disease (60%). Idiopathic angular deformity showed an 89.5% success rate with guided growth. In our hands, guided growth had an 80.5% success rate when all diagnoses were considered. We continue to advocate the use of guided growth as a successful treatment option for skeletally immature patients with limb deformity however caution should be employed when considering its use in certain patient groups. Level III, retrospective cohort study.

Expanding the Clinical Features of Schimke Immuno-Osseous Dysplasia: A New Patient with a Novel Variant and Novel Clinical Findings.

Schimke Immuno-Osseous Dysplasia (SIOD) (MIM:242900) is an ultra-rare autosomal recessive pan-ethnic pleiotropic disease. Typical findings of this syndrome are steroid-resistant nephrotic syndrome, cellular immunodeficiency and spondyloepiphyseal dysplasia and facial dysmorphism. Biallelic variants in the SMARCAL1 gene cause SIOD. The five-and-half-year-old female patient was evaluated because of short stature, dysmorphism, hypercalcemia, hypophosphatemia and elevated FSH levels. Karyotype analysis and array-CGH testing were normal. Clinical Exome Sequencing was performed via next-generation sequencing to analyze genes associated with hypophosphatemia. No pathogenic variant was detected. The subsequent detection of proteinuria during her follow-up for cross-fused ectopic left kidney ultimately facilitated the diagnosis of SIOD, although no obvious spondyloepiphyseal dysplasia was detected. Re-analysis of CES revealed a novel homozygous c.2422_2427+9delinsA pathogenic variant in the SMARCAL1. One hundred twenty-five SIOD cases from 38 literature reporting SMARCAL1 gene pathogenic variants were reviewed to investigate whether hypercalcemia, hypophosphatemia and elevated FSH levels had been previously reported in SIOD patients. This review revealed that this was the first time these findings had been reported in a SIOD patient. This report expands not only the phenotypic but also genotypic spectrum of SIOD.

Detection of Spondyloepiphyseal Dysplasia Phenotype with CHST3 Mutation in an Asian Indian Family and Outcomes of Index and Subsequent Pregnancy

Abstract CHST3-related skeletal dysplasia is an autosomal recessive disorder with a prenatal onset. Variations in the CHST3 gene are associated with spondyloepiphyseal dysplasia with short stature of prenatal onset; dislocation of the knees, hips or elbows; club feet; postnatal limitation of range of motion of large joints; and progressive kyphosis, occasional scoliosis and minor heart valve dysplasia. The identification of pathogenic variants in the family is helpful for carrier and prenatal testing. We describe the prenatal identification of spondyloepiphyseal dysplasia with CHST3 mutation in the index pregnancy of an Asian Indian woman and the outcome of the subsequent pregnancy.

Total Knee Arthroplasty in Patients Who Have Skeletal Dysplasia: A Center’s Experience With a Mean 9-Year Follow-Up

BackgroundTotal knee arthroplasty (TKA) in patients who have skeletal dysplasia (SD) is a technically challenging surgery due to deformity, joint contracture, and associated comorbidities. Patients presenting with this condition have traditionally been treated with conservative measures, leading to poor outcomes. The aim of this study was to follow-up on patients who had SD following TKA, specifically with regards to clinical outcomes. MethodsA total of 31 knees (22 patients) with SD that had undergone TKA in our institution were included in our study. The mean follow-up from index surgery was 110.3 months (range: 20 to 291). The type of dysplasia, implant used, and clinical outcomes with patient-reported outcome measures are presented. ResultsThere were 8 patients (36.3%) who had a diagnosis of achondroplasia, followed by multiple epiphyseal dysplasia (31.8%) and spondyloepiphyseal dysplasia (22.7%). There were 14 men and 8 women who had a mean age of 51 years (range: 28 to 73). Custom implants were required in 12 cases (38.7%), custom jigs were used in 6 cases (19.4%), and robotic-assisted surgery was used in 2 (6.5%) TKAs. Hinged prostheses were used in 17 cases (54.8%), posterior-stabilized in 9 (29.0%), and cruciate-retaining implants in 5 (16.1%). There was 1 patient who sustained an intraoperative medial tibial plateau fracture treated with concomitant open reduction and internal fixation. There was 1 revision that occurred during the follow-up period with a patella resurfacing for continued anterior knee pain. Postoperatively, Oxford Knee Scores improved on average by 12.2 points. The 10-year and 20-year all-cause revision-free survival was 96.8, respectively. ConclusionsDespite the technical challenges and complexity associated with this unique patient cohort, we demonstrated excellent implant survivorship and clinical outcomes post-TKA with mid-term to long-term follow-up of more than 20 years. We recommend preoperative cross-sectional imaging for precise planning and implant templating with multidisciplinary team decision-making. Despite our results, functional outcomes remain inferior to primary arthroplasty within the general population, although we still recommend this treatment modality to appropriately counseled patients. Level of EvidenceIII.

Further characterization of ARSK-related mucopolysaccharidosis type 10.

Mucopolysaccharidosis type 10 is caused by biallelic variants in ARSK, which encodes for a lysosomal sulfatase. To date, seven patients with a mild phenotype resembling spondyloepiphyseal dysplasia or multiple epiphyseal dysplasia have been described. In this report, we present two novel ARSK variants and report clinical and radiological findings of three patients. The patients' initial complaints were hip or knee pain and a waddling gait. All patients showed normal intelligence, normal hearing and eye examinations, and none had organomegaly. While typical dysostosis multiplex findings were not observed, mild platyspondyly with anterior beaking of some vertebral bodies, irregular vertebral endplates, wide ribs, inferior tapering of the ilea with a poorly developed acetabulum, irregularity of the central part of the femoral head, delayed ossification of the carpals were noted. Remarkably, all patients showed metaphyseal striation of the long bones, a crucial diagnostic clue to identify ARSK-related MPS type 10. Interestingly, vertebral involvement regressed during follow-up. On the other hand, hip dysplasia progressed in all patients. In conclusion, this study provides valuable long-term results on a recently discovered form of MPS.

A Novel Missense Variant in the CHST3 Underlies Spondyloepiphyseal Dysplasia with Congenital Joint Dislocations

Background: Spondyloepiphyseal dysplasia (SED) is characterized by skeletal dysplasia and multiple joint dislocations. SEDs encompass various types, such as SED congenita, SED tarda (SED-T), SED with congenital joint dislocations (SED-CJD), SED stanescu, and SED-T with progressive arthropathy. Methods and Results: In the present study, we clinically and genetically characterized a consanguineous Pakistani family with SED-CJD. The affected member showed large joint dislocation, spinal deformities, and previously unreported facial features. Exome sequencing followed by Sanger sequencing revealed a missense variant, [c.601T>A; p.(Tyr201Asn)], in the CHST3. Conclusion: This study has not only expended the mutation spectrum in the gene CHST3 but also will facilitate diagnosis and genetic counseling of related features in the Pakistani population.

Total hip arthroplasty in patients with common pediatric hip orthopedic pathology.

Literature regarding total hip arthroplasty for pediatric hip diseases is scarce. This review aims to portray the various orthopedic conditions of childhood that can lead to significant impairment of the hip joint and, ultimately, to total hip arthroplasty in adolescence and adulthood. In total, 61 out of 3666 articles were selected according to (1) the diagnosis of one of the 12 pediatric hip pathologies (Legg-Perthes-Calvé disease, developmental dysplasia of the hip, slipped capital femoral epiphysis, neuromuscular hip dysplasia, post-traumatic avascular necrosis of the proximal femur, juvenile rheumatoid arthritis, achondroplasia, spondyloepiphyseal dysplasia, mucopolysaccharidosis, mucolipidosis, hip infections, and tumors) that required total hip arthroplasty; (2) minimum follow-up of 16 months; (3) assessed outcome with a clinical or radiologic score; (4) Methodological Items for Non-Randomized Studies quality score of 9 or higher. The following information for each pathology was retrieved: mean age at total hip arthroplasty, reason for total hip arthroplasty, type of total hip arthroplasty, surgical technique, mean follow-up, and outcomes. Overall, the mean age at total hip arthroplasty for pediatric hip disease is in the sixth and seventh decade, except for tumors and skeletal dysplasias. The reason for performing total hip arthroplasty is often osteoarthrosis and abnormal anatomy. Prosthesis types change based on patient's conditions and technological advances; custom-made implants are used for tumors, juvenile rheumatoid arthritis, and skeletal dysplasias; for other diseases, the most frequent are modular cementless implants. Outcomes are generally good, and all studies portray functional and pain improvements. Total hip arthroplasty is performed more frequently than in the past in patients with pediatric hip pathologies; it enhances patients' quality of life by reducing pain and improving function. However, revision rate in these patients is not negligible.

Exome Sequencing Reveals Biallelic Mutations in MBTPS1 Gene in a Girl with a Very Rare Skeletal Dysplasia

The Kondo-Fu type of spondyloepiphyseal dysplasia (SEDKF) is a rare skeletal dysplasia caused by homozygous or compound heterozygous mutations in the MBTPS1 gene. The MBTPS1 gene encodes a protein that is involved in the regulation of cholesterol and fatty acid metabolism. Mutations in MBTPS1 can lead to reduced levels of these lipids, which can have a number of effects on development, including skeletal anomalies, growth retardation, and elevated levels of blood lysosomal enzymes. This work reports the case of a 5-year-old girl with SEDKF. The patient had a severely short stature and a number of skeletal anomalies, including kyphosis, pectus carinatum, and reduced bone mineral density. She also had early onset cataracts and inguinal hernias. Genetic testing revealed two novel compound heterozygous variants in the MBTPS1 gene. These variants are predicted to disrupt the function of the MBTPS1 protein, which is consistent with the patient’s clinical presentation. This case report adds to the growing body of evidence that mutations in the MBTPS1 gene are causal of SEDKF. We summarized the features of previous reported cases (with age ranges from 4 to 24 years) and identified that 80% had low stature, 70% low weight, 80% had bilateral cataracts and 70% showed Spondyloepiphyseal dysplasia on X-rays. The findings of this study suggest that SEDKF is a clinically heterogeneous disorder that can present with a variety of features. Further studies are needed to better understand the underlying mechanisms of SEDKF and to develop more effective treatments.

Total Hip Arthroplasty with Extra-small Femoral Stems in Extremely Hypoplastic Femurs: A Case-Series Study.

Total hip arthroplasty (THA) in patients with hypoplastic femurs presents a significant challenge to orthopedic surgeons due to the limited space available for implant placement. Therefore, the extra-small femoral stems have been proposed as a solution to this problem, but there are limited data on the outcomes. We aimed to evaluate clinical and radiological outcomes of THA in patients with extremely hypoplastic femurs using the Bencox CM stem (Corentec), an extra-small femoral stem. We included 6 hips from 4 patients. The mean age of the patients was 41.2 years (range, 19.6-60.4 years). The mean height was 135.1 cm (range, 113.6-150.0 cm) with a mean body mass index of 25.7 kg/m2 (range, 21.3-31.1 kg/m2). The diagnoses for THA were sequelae of septic arthritis in childhood, pseudoachondroplasia, spondyloepiphyseal dysplasia, and juvenile rheumatoid arthritis. Preoperative computed tomography scans were conducted to assess the extent of proximal femoral hypoplasia. The clinical outcomes were assessed using the modified Harris Hip Score, while the radiological outcomes were evaluated using radiographs. The mean follow-up was 2.3 years (range, 1.0-5.9 years). The average modified Harris Hip Score improved to 88.8 at the final follow-up. Intraoperative femoral fractures occurred in 2 cases (33.3%). During the follow-up, 1 stem underwent varus tilting from postoperative 6 weeks to 6 months without subsidence. Otherwise, all stems showed good osteointegration at the latest follow-up. No hip dislocations, periprosthetic joint infection, or loosening of the prosthesis occurred. The use of extra-small femoral stems in THA for extremely hypoplastic femurs can provide reasonable clinical and radiological outcomes with minimal complications. We suggest that this femoral stem could be a viable option for patients with extremely hypoplastic femurs.

Rare Case of a Dyggve-Melchior-Clausen Syndrome Revealed by a Spinal Cord Compression

Dyggve-Melchior-Clausen syndrome (DMSC) is an rare autosomal recessive skeletal disorder that belongs to the category of spondyloepiphyseal dysplasia. The present work reports a case of DMCS in a nine- year-old kid who was admitted for spinal cord compression accompanied by mental retardation and dysmorphic syndrome. The patient had shown a C1-C2 dislocation with compression of the bulbo-medullary junction, platyspondyly with double ondulation of all the vertebral endplates, widely open acetabulums and epi- metaphyseal dysplasia of the femoral heads. Discussion: The syndrome is clinically characterized by a staturo- ponderal delay of varying severity. Radiological characteristics consist of a scalloped appearance of the iliac wings, spondyloepimetaphyseal dysplasia and platyspondyly. The diagnosis of Dyggve-Melchior-Clausen syndrome can be suspected after a clinical evaluation, a detailed patient history, and identification of characteristic clinical and radiological signs.

Os odontoideum: database analysis of 260 patients regarding etiology, associated abnormalities, and literature review.

Since the first description of os odontoideum in 1886, its origin has been debated. Numerous case series and reports show both a possible congenital origin and origin from the secondary to craniovertebral junction (CVJ) trauma. We conducted a detailed analysis of 260 surgically treated cases to document the initial symptoms, age groups, radiographic findings, and associated abnormalities, aiming to enhance the confirmation of the etiology. A literature search (1970-2022) was performed to correlate our findings. A total of 260 patients underwent surgical management of a referral database of 520 cases (1978-2022). All patients were examined by plain radiography and myelotomography as needed until 1984, and since then, CT and MRI have been employed. History of early childhood (aged below 6 years) CVJ trauma was investigated, including obtaining emergency department's initial radiographs from the referral and subsequent follow-up. Associated radiographic and systemic abnormalities were noted, and the atlas development was followed. The age of the patients ranged from 4 to 68 years, mostly between 10 and 20 years. There were 176 males and 86 females. Orthotopic os odontoideum was identified in 24 patients, and 236 patients had dystopic os odontoideum. Associated abnormalities were found in 94 of 260 patients, with 73 exhibiting syndromic abnormalities and 21 having Chiari I malformation. Two sets of twins had spondyloepiphyseal dysplasia. Of 260 patients, 156 experienced early childhood trauma /. Among these, 54 initially presented with normal radiographs but later demonstrated anterior atlas hypertrophy. In addition, a smaller posterior C1 arch was observed, leading to the development of os odontoideum. Two children had initial CVJ trauma as documented by MRI, with subsequent classical findings of os odontoideum and atlas changes. Syndromic patients had an earlier presentation. The literature reviewed confirms the multifactorial etiology. The early presentation and associated abnormalities (such as Down syndrome, Klippel-Feil syndrome, Chiari I malformation, spondyloepiphyseal dysplasia, Morquio syndrome, and others) along with case reports documenting familial, hereditary, and twin presentations strongly support a congenital origin. Likewise, surgical complications are more prevalent in syndromic patients (40%) compared to 15% in other cases, as reported in the literature. The documentation of normal odontoid in early childhood trauma cases followed by the later development of os odontoideum provides evidence supporting trauma as an etiological factor. This process also involves vascular changes in both the atlas and the formation of os odontoideum. Associated abnormalities exhibit an earlier presentation and are only seen in cases with a non-traumatic origin.

Surgical treatment of atlantoaxial dysplasia and scoliosis in spondyloepiphyseal dysplasia congenita: A case report

BACKGROUND Spondyloepiphyseal dysplasia congenita (SEDC) is a rare autosomal dominant hereditary disease caused by COL2A1 mutations. SEDC primarily involves the skeletal system, with typical clinical manifestations, including short stature, hip dysplasia, and spinal deformity. Due to the low incidence of SEDC, there are only a few case reports regarding the surgical treatment of SEDC complicated with spinal deformities. CASE SUMMARY We report a case of a 16-year-old male patient with SEDC. He presented with typical short stature, atlantoaxial dysplasia, scoliosis, and hip dysplasia. Cervical magnetic resonance imaging showed spinal canal stenosis at the atlas level and cervical spinal cord compression with myelopathy. The scoliosis was a right thoracic curve with a Cobb angle of 65°. He underwent atlantoaxial reduction, decompression, and internal fixation from C1–C2 to relieve cervical myelopathy. Three months after cervical surgery, posterior correction surgery for scoliosis was performed from T3 to L4. Scoliosis was corrected from 66° to 8° and remained stable at 2-year follow-up. CONCLUSION This is the first case report of a patient with SEDC who successfully underwent surgery for atlantoaxial dysplasia and scoliosis. The study provides an important reference for the surgical treatment of SEDC complicated with spinal deformities.

Role of trafficking protein particle complex 2 in medaka development.

The skeletal dysplasia spondyloepiphyseal dysplasia tarda (SEDT) is caused by mutations in the TRAPPC2 gene, which encodes Sedlin, a component of the trafficking protein particle (TRAPP) complex that we have shown previously to be required for the export of type II collagen (Col2) from the endoplasmic reticulum. No vertebrate model for SEDT has been generated thus far. To address this gap, we generated a Sedlin knockout animal by mutating the orthologous TRAPPC2 gene (olSedl) of Oryzias latipes (medaka) fish. OlSedl deficiency leads to embryonic defects, short size, diminished skeletal ossification and altered Col2 production and secretion, resembling human defects observed in SEDT patients. Moreover, SEDT knock-out animals display photoreceptor degeneration and gut morphogenesis defects, suggesting a key role for Sedlin in the development of these organs. Thus, by studying Sedlin function in vivo, we provide evidence for a mechanistic link between TRAPPC2-mediated membrane trafficking, Col2 export, and developmental disorders.

Specific heterozygous variants in MGP lead to endoplasmic reticulum stress and cause spondyloepiphyseal dysplasia

Matrix Gla protein (MGP) is a vitamin K-dependent post-translationally modified protein, highly expressed in vascular and cartilaginous tissues. It is a potent inhibitor of extracellular matrix mineralization. Biallelic loss-of-function variants in the MGP gene cause Keutel syndrome, an autosomal recessive disorder characterized by widespread calcification of various cartilaginous tissues and skeletal and vascular anomalies. In this study, we report four individuals from two unrelated families with two heterozygous variants in MGP, both altering the cysteine 19 residue to phenylalanine or tyrosine. These individuals present with a spondyloepiphyseal skeletal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. We investigated the cellular and molecular effects of one of the heterozygous deleterious variants (C19F) using both cell and genetically modified mouse models. Heterozygous ‘knock-in’ mice expressing C19F MGP recapitulate most of the skeletal anomalies observed in the affected individuals. Our results suggest that the main underlying mechanism leading to the observed skeletal dysplasia is endoplasmic reticulum stress-induced apoptosis of the growth plate chondrocytes. Overall, our findings support that heterozygous variants in MGP altering the Cys19 residue cause autosomal dominant spondyloepiphyseal dysplasia, a condition distinct from Keutel syndrome both clinically and molecularly.

Functional analysis of a novel nonsense variant c.91A>T of the TRAPPC2 gene in a Chinese family with X-linked recessive autosomal spondyloepiphyseal dysplasia tarda.

Spondyloepiphyseal dysplasia tarda (SEDT) is a condition involving late-onset, X-linked recessive skeletal dysplasia caused by mutations in the TRAPPC2 gene. In this paper, we identified a novel nonsense variant in a SEDT pedigree and analyzed the function of the variant in an attempt to explain the new pathogenesis of the TRAPPC2 protein in SEDT. Briefly, DNA and RNA samples from the peripheral blood of SEDT individuals were prepared. The causative variant in the Chinese SEDT family was identified by clinic whole-exome sequencing analysis. Then, we observed the mRNA expression of TRAPPC2 in patients and the mutant TRAPPC2 level in vitro and analyzed the protein stability and subcellular distribution by cell fluorescence and Western blotting. We also investigated the effect of TRAPPC2 knockdown on the expression and secretion of COL2A1 in SW1353 cells or primary human chondrocytes. Herein, we found a nonsense variant, c.91A>T, of the TRAPPC2 gene in the pedigree. TRAPPC2 mRNA expression levels were significantly decreased in the available peripheral blood cell samples of two affected patients. An in vitro study showed that the mutant plasmid exhibited significantly lower mRNA and protein of TRAPPC2, and the mutant protein changed its membrane distribution. TRAPPC2 knockdown resulted in decreased COL2A1 expression and collagen II secretions. Our data indicate that the novel nonsense variant, c.91A>T, of the TRAPPC2 gene is the cause of SEDT in this pedigree. The variant results in a lowered expression of TRAPPC2 and then affects the COL2A1 expression and collagen II secretions, which may explain the mechanism of loss of function of the variant.

Psychosocial impacts of caring for a child with a genetic disorder in Accra, Ghana.

Caregivers caring for a child with a genetic condition may experience psychosocial distress, which may be compounded by the context in which the caring takesplace. Few studies have examined psychosocial distress and support among caregivers caring for a child with a genetic disorder in low-middle-income countries such as Ghana. The purpose of the current study was to investigate the psychosocial impacts of caring for a child with a genetic disorder in an urban setting in Ghana's capital, Accra. We conducted individual interviews among 17 caregivers who were taking care of children with various genetic disorders including, albinism, Edward's syndrome, osteogenesis imperfecta, sickle cell disease, and spondyloepiphyseal dysplasia congenita. Thematic analysis of the data revealed three main themes on the psychosocial impacts, including: (1) self-blame, guilt, and shame; (2) sleep and mood disturbances; and (3) discrimination and stigmatization. We observed three themes about support: (1) psychological support; (2) family and community support; and (3) institutional support. Participants reported limited support from professionals such as psychologists. Discussion focuses on the supportive care needs of caregivers and implications for genetic counselling awareness, advocacy, and training.

TOTAL KNEE ARTHROPLASTY IN PATIENTS WITH SKELETAL DYSPLASIA

AbstractIntroductionTotal knee replacement (TKR) in patients with skeletal dysplasia is technically challenging surgery due to deformity, joint contracture, and associated co-morbidities. The aim of this study is to follow up patients with skeletal dysplasia following a TKR.MethodologyWe retrospectively reviewed 22 patients with skeletal dysplasia who underwent 31 TKRs at our institution between 2006 and 2022. Clinical notes, operative records and radiographic data were reviewed.ResultsAchondroplasia was the most common skeletal dysplasia (8), followed by Chondrodysplasia punctata (7) and Spondyloepiphyseal dysplasia (5). There were fourteen men and eight women with mean age of 51 years (28 to 73). The average height of patients was 1.4 metres (1.16–1.75) and the mean weight was 64.8 Kg (34.3–100). The mean follow up duration was 68.32 months (1–161). Three patients died during follow up. Custom implants were required in twelve patients (38.71%). Custom jigs were utilised in six patients and two patients underwent robotic assisted surgery. Hinged TKR was used in seventeen patients (54.84%), posterior stabilised TKR in nine patients (29.03%), and cruciate retaining TKR in five patients (16.13%). One patient underwent a patella resurfacing for persistent anterior knee pain and another had an intra-operative medial tibial plateau fracture which was managed with fixation. No revisions occurred during the follow up period.ConclusionDespite the technical challenges and complexity of TKR within this unique patient group, we demonstrate good implant survivorship during the study period. Cross sectional imaging is recommended preoperatively for precise planning and templating.

Morquio A Syndrome Case Report and Literature Review

Morquio A syndrome is an autosomal recessive disorder, one of 50 lysosomal storage diseases (LSDs), and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme causes specific glycosaminoglycan (GAG) accumulation: keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced in the cartilage, therefore, the undegraded substrates accumulate mainly in cartilage and in its extracelluar matrix (ECM), causing direct leads to direct impact on cartilage and bone development and leading to the resultant systemic skeletal spondyloepiphyseal dysplasia. Chondrogenesis, the earliest phase of skeletal formation that leads to cartilage and bone formation is controlled by cellular interactions with the ECM, growth and differentiation factors and other molecules that affect signaling pathways and transcription factors in a temporal-spatial manner. In Morquio A patients, in early childhood or even at birth, the cartilage is disrupted presumably as a result of abnormal chondrogenesis and/or endochondral ossification. The unique clinical features are characterized by a marked short stature, odontoid hypoplasia, protrusion of the chest, kyphoscoliosis, platyspondyly, coxa valga, abnormal gait, and laxity of joints.In spite of many descriptions of the unique clinical manifestations, diagnosis delay still occurs. The pathogenesis of systemic skeletal dysplasia in Morquio A syndrome remains an enigmatic challenge. In this review article, screening, diagnosis, pathogenesis and current and future therapies of Morquio A are discussed.

Variability of clinical manifestations in the child with Roifman syndrome

Introduction. Roifman syndrome is a rare hereditary autosomal recessive disease, often associated with primary immunodeficiency and spondyloepiphyseal dysplasia. The cause of the disease is a splicing disorder due to a mutation of the RNU4ATAC gene with the formation of an incorrect protein structure, which in turn leads to clinical polymorphism.
 Purpose: demonstration of own clinical observation of the 5-year girl with Roifman syndrome.
 Materials and methods. An analysis of the literature on the stigmas of dysembriogenesis, clinical manifestations, changes in the immune system that determine the formation of Roifman syndrome was carried out.
 Results. The features of the course and variability of manifestations in the particular patient with Roifman syndrome are described. The variety and non-specificity of clinical symptoms in Roifman syndrome in the 5-year girl is shown. Timely diagnosis after complete sequencing by Sanger made it possible to identify a complex heterozygous mutation in the RNU4ATAC gene and start adequate therapy.