Subject(s)
Osteochondrodysplasias , Humans , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnostic imaging , Osteochondrodysplasias/diagnosis , Congenital Bone Marrow Failure Syndromes/drug therapy , Congenital Bone Marrow Failure Syndromes/complications , Male , Female , Treatment Outcome , Pancytopenia/etiology , Pancytopenia/drug therapy , Cytopenia , Anemia, RefractoryABSTRACT
RATIONALE: Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene. PATIENT CONCERNS: Here, we report 2 cases of Korean children with CHH-AD. DIAGNOSES: In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES. INTERVENTIONS: The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups. OUTCOMES: Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis. LESSONS SUBSECTIONS: Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD.
Subject(s)
Hair , Hirschsprung Disease , Mutation , Osteochondrodysplasias , Humans , Republic of Korea , Osteochondrodysplasias/genetics , Osteochondrodysplasias/diagnosis , Male , Female , Hair/abnormalities , Hirschsprung Disease/genetics , Hirschsprung Disease/diagnosis , Dwarfism/genetics , Dwarfism/diagnosis , Primary Immunodeficiency Diseases/genetics , Primary Immunodeficiency Diseases/diagnosis , Hypotrichosis/genetics , Hypotrichosis/diagnosis , Exome Sequencing , Infant , Child, Preschool , Endoribonucleases/genetics , Child , RNA, Long NoncodingABSTRACT
BACKGROUND: Given the rarity of tracheobronchopathia osteochondroplastica (TO), many young doctors in primary hospitals are unable to identify TO based on bronchoscopy findings. OBJECTIVES: To build an artificial intelligence (AI) model for differentiating TO from other multinodular airway diseases by using bronchoscopic images. DESIGN: We designed the study by comparing the imaging data of patients undergoing bronchoscopy from January 2010 to October 2022 by using EfficientNet. Bronchoscopic images of 21 patients with TO at Anhui Chest Hospital from October 2019 to October 2022 were collected for external validation. METHODS: Bronchoscopic images of patients with multinodular airway lesions (including TO, amyloidosis, tumors, and inflammation) and without airway lesions in the First Affiliated Hospital of Guangzhou Medical University were collected. The images were randomized (4:1) into training and validation groups based on different diseases and utilized for deep learning by convolutional neural networks (CNNs). RESULTS: We enrolled 201 patients with multinodular airway disease (38, 15, 75, and 73 patients with TO, amyloidosis, tumors, and inflammation, respectively) and 213 without any airway lesions. To find multinodular lesion images for deep learning, we utilized 2183 bronchoscopic images of multinodular lesions (including TO, amyloidosis, tumor, and inflammation) and compared them with images without any airway lesions (1733). The accuracy of multinodular lesion identification was 98.9%. Further, the accuracy of TO detection based on the bronchoscopic images of multinodular lesions was 89.2%. Regarding external validation (using images from 21 patients with TO), all patients could be diagnosed with TO; the accuracy was 89.8%. CONCLUSION: We built an AI model that could differentiate TO from other multinodular airway diseases (mainly amyloidosis, tumors, and inflammation) by using bronchoscopic images. The model could help young physicians identify this rare airway disease.
Subject(s)
Bronchoscopy , Osteochondrodysplasias , Predictive Value of Tests , Tracheal Diseases , Humans , Tracheal Diseases/diagnostic imaging , Tracheal Diseases/pathology , Tracheal Diseases/diagnosis , Middle Aged , Male , Female , Adult , Diagnosis, Differential , Osteochondrodysplasias/diagnostic imaging , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/pathology , Reproducibility of Results , Deep Learning , Aged , China , Image Interpretation, Computer-Assisted , Neural Networks, Computer , Artificial IntelligenceABSTRACT
Introduction: Osteochondroplastic tracheobronchopathy is a rare benign chronic disease of unknown etiology. Bronchoscopy remains the gold standard for diagnosing osteochondroplastic tracheobronchopathy. Its typical findings are described as a cobblestone, rock garden, mountainscape, or stalactite cave appearance. The present work aims to show the main clinical features of this rare pathology. Clinical cases: The clinical data of four middle-aged patients, three men and one woman, were analyzed. The main clinical symptoms were chronic cough, dyspnea, and dysphonia. The patient's preliminary diagnosis was made by computed axial tomography of the chest, confirmed by bronchoscopy and histopathological examination. Treatment included medication for symptoms and, in one case, cryosurgery and argon plasma coagulation. Discussion: Diagnosing osteochondroplastic tracheobronchopathy was not easy, given its uncommon nature and non-specific symptoms often found in other pathologies. No case series articles on this pathology have been published in Peru. Therefore, we used the original articles published in other countries to reference our findings. Conclusion: Osteochondroplastic tracheopathy is a benign disease that typically affects adults. Men are more likely to be affected. Its clinical manifestations are non-specific and frequently of pharyngeal origin, and the cause is not yet defined. Chest computed axial tomography combined with bronchoscopy are the main diagnostic procedures. There is no standard treatment with consistent therapeutic effects.
Introducción: La traqueobroncopatía osteocondroplástica es una rara enfermedad crónica benigna de etiología desconocida. La broncoscopía sigue siendo el estándar de oro para el reconocimiento de traqueopatía osteocondroplástica. Sus hallazgos típicos se describen como un empedrado, un jardín de rocas, una apariencia de paisaje montañoso o de una cueva con estalactitas. El objetivo del presente trabajo es mostrar las principales características clínicas de una patología poco conocida. Casos clínicos: Se analizaron los datos clínicos de cuatro pacientes de mediana edad, tres fueron hombres y una mujer. Los principales síntomas clínicos fueron tos crónica, disnea, disfonía. Los pacientes tuvieron un diagnóstico preliminar mediante tomografía axial computarizada de tórax, confirmado por examen video broncoscópico e histopatológico. El tratamiento incluyó medicamentos para los síntomas y en un solo caso criocirugía y coagulación con argón plasma. Discusión: El diagnóstico de traqueobroncopatía osteocondroplástica no fue sencillo por ser una entidad rara, cuyos síntomas son inespecíficos y muy frecuentes en otras patologías. En Perú no se han publicado artículos de serie de casos sobre esta patología. Por lo tanto, tomamos como referencia artículos originales publicados en otros países para compararlos con nuestros hallazgos. Conclusión: La traqueopatía osteocondroplástica es una enfermedad benigna que predispone a los adultos, los hombres tienen más probabilidades de verse afectados. Sus manifestaciones clínicas son inespecíficas; frecuentemente de origen faríngeo y la causa no está aún definida. La tomografía axial computarizada de tórax combinada con video broncoscopía son los principales procedimientos para el diagnóstico. No existe un estándar de tratamiento con efectos terapéuticos consistentes.
Subject(s)
Bronchial Diseases , Osteochondrodysplasias , Tracheal Diseases , Female , Humans , Male , Middle Aged , Bronchial Diseases/diagnosis , Bronchial Diseases/pathology , Bronchoscopy , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/pathology , Tomography, X-Ray Computed , Tracheal Diseases/diagnosis , Tracheal Diseases/therapy , Tracheal Diseases/pathologySubject(s)
Hair/abnormalities , Hirschsprung Disease , Osteochondrodysplasias , Osteochondrodysplasias/congenital , Primary Immunodeficiency Diseases , RNA, Long Noncoding , Humans , Osteochondrodysplasias/mortality , Osteochondrodysplasias/genetics , Osteochondrodysplasias/diagnosis , Primary Immunodeficiency Diseases/diagnosis , Primary Immunodeficiency Diseases/mortality , Risk Factors , Hirschsprung Disease/mortality , Hirschsprung Disease/genetics , Hirschsprung Disease/diagnosis , Male , Female , Infant , Child, Preschool , Hypotrichosis/genetics , Hypotrichosis/diagnosis , Hypotrichosis/mortality , ChildABSTRACT
Biallelic variants in RSPRY1 have been found to result in spondyloepimetaphyseal dysplasia. Two siblings presenting with short stature, facial dysmorphism, progressive vertebral defects, small epiphysis, cupping and fraying of metaphyses, brachydactyly, and short metatarsals harbored a homozygous missense variant c.1652G>A;p.(Cys551Tyr) in the RSPRY1 gene. The phenotype in our patients resembles spondyloepimetaphyseal dysplasia, Faden-Alkuraya type. Thus, our study provides further evidence to support the association of RSPRY1 variants with spondyloepimetaphyseal dysplasia. We observed joint dislocation as a novel clinical feature of this condition.
Subject(s)
Osteochondrodysplasias , Phenotype , Siblings , Child , Female , Humans , Homozygote , Mutation/genetics , Mutation, Missense/genetics , Osteochondrodysplasias/genetics , Osteochondrodysplasias/pathology , Osteochondrodysplasias/diagnosis , Pedigree , DNA-Binding Proteins/geneticsABSTRACT
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.
Subject(s)
Phenotype , Adolescent , Child , Child, Preschool , Female , Humans , Male , Mutation/genetics , N-Acetylgalactosamine-4-Sulfatase/genetics , Osteochondrodysplasias/genetics , Osteochondrodysplasias/pathology , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/diagnostic imaging , RadiographyABSTRACT
Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.
Subject(s)
Adalimumab , Granuloma , Hair , Osteochondrodysplasias , Primary Immunodeficiency Diseases , Skin Ulcer , Humans , Male , Hair/abnormalities , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/diagnosis , Adalimumab/therapeutic use , Skin Ulcer/etiology , Skin Ulcer/drug therapy , Granuloma/drug therapy , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/congenital , Hirschsprung Disease/complications , Hirschsprung Disease/diagnosis , Middle Aged , Hypotrichosis/diagnosisABSTRACT
Skeletal dysplasia, also called osteochondrodysplasia, is a category of disorders affecting bone development and children's growth. Up to 552 genes, including fibroblast growth factor receptor 3 (FGFR3), have been implicated by pathogenic variations in its genesis. Frequently identified causal mutations in osteochondrodysplasia arise in the coding sequences of the FGFR3 gene: c.1138G>A and c.1138G>C in achondroplasia and c.1620C>A and c.1620C>G in hypochondroplasia. However, in some cases, the diagnostic investigations undertaken thus far have failed to identify the causal anomaly, which strengthens the relevance of the diagnostic strategies being further refined. We observed a Caucasian adult with clinical and radiographic features of achondroplasia, with no common pathogenic variant. Exome sequencing detected an FGFR3(NM_000142.4):c.1075+95C>G heterozygous intronic variation. In vitro studies showed that this variant results in the aberrant exonization of a 90-nucleotide 5' segment of intron 8, resulting in the substitution of the alanine (Ala359) for a glycine (Gly) and the in-frame insertion of 30 amino acids. This change may alter FGFR3's function. Our report provides the first clinical description of an adult carrying this variant, which completes the phenotype description previously provided in children and confirms the recurrence, the autosomal-dominant pathogenicity, and the diagnostic relevance of this FGFR3 intronic variant. We support its inclusion in routinely used diagnostic tests for osteochondrodysplasia. This may increase the detection rate of causal variants and therefore could have a positive impact on patient management. Finally, FGFR3 alteration via non-coding sequence exonization should be considered a recurrent disease mechanism to be taken into account for new drug design and clinical trial strategies.
Subject(s)
Achondroplasia , Osteochondrodysplasias , Child , Adult , Humans , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Achondroplasia/diagnosis , Achondroplasia/genetics , Achondroplasia/pathology , Mutation , Exons , Phenotype , Receptor, Fibroblast Growth Factor, Type 3/geneticsABSTRACT
Skeletal dysplasias (SKDs) are a heterogeneous group of more than 750 genetic disorders characterized by abnormal development, growth, and maintenance of bones or cartilage in the human skeleton. SKDs are often caused by variants in early patterning genes and in many cases part of multiple malformation syndromes and occur in combination with non-skeletal phenotypes. The aim of this study was to investigate the underlying genetic cause of congenital SKDs in highly consanguineous Pakistani families, as well as in sporadic and familial SKD cases from India using multigene panel sequencing analysis. Therefore, we performed panel sequencing of 386 bone-related genes in 7 highly consanguineous families from Pakistan and 27 cases from India affected with SKDs. In the highly consanguineous families, we were able to identify the underlying genetic cause in five out of seven families, resulting in a diagnostic yield of 71%. Whereas, in the sporadic and familial SKD cases, we identified 12 causative variants, corresponding to a diagnostic yield of 44%. The genetic heterogeneity in our cohorts was very high and we were able to detect various types of variants, including missense, nonsense, and frameshift variants, across multiple genes known to cause different types of SKDs. In conclusion, panel sequencing proved to be a highly effective way to decipher the genetic basis of SKDs in highly consanguineous families as well as sporadic and or familial cases from South Asia. Furthermore, our findings expand the allelic spectrum of skeletal dysplasias.
Subject(s)
Consanguinity , Pedigree , Humans , Male , Female , Pakistan/epidemiology , India/epidemiology , Osteochondrodysplasias/genetics , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/pathology , Phenotype , Child , Mutation , Bone Diseases, Developmental/genetics , Genetic Predisposition to Disease , Child, Preschool , High-Throughput Nucleotide Sequencing , Genetic HeterogeneityABSTRACT
Tracheobronchopathia osteochondroplastica (TO) is an uncommon non-malignant tracheal ailment characterized by the existence of numerous bone and/or cartilage nodules in the submucosa of the trachea and bronchi. At present, there is a lack of standardized treatment recommendations for TO. This article presents two instances of severe tracheal stenosis caused by TO, which were effectively managed through the implementation of bronchoscopic stent placement and rigid bronchoscopy curettage, respectively. Both cases exhibited favorable outcomes, providing novel insights and references for the treatment of TO. Laryngoscope, 134:3093-3095, 2024.
Subject(s)
Bronchoscopy , Osteochondrodysplasias , Tracheal Diseases , Humans , Bronchoscopy/methods , Tracheal Diseases/surgery , Tracheal Diseases/diagnosis , Osteochondrodysplasias/surgery , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnosis , Male , Tracheal Stenosis/surgery , Female , Stents , Middle Aged , Curettage/methods , Trachea/surgeryABSTRACT
The autosomal dominant spondylometaphyseal dysplasia Sutcliff type or corner fracture type FN1-related is characterized by a combination of metaphyseal irregularities simulating fractures ("corner fractures"), developmental coxa vara, and vertebral changes. It is linked to heterozygous mutations in FN1 and COL2A1. Vertebral changes as delayed vertebral ossification, ovoid vertebral bodies, anterior vertebral wedging, and platyspondyly have been observed in this condition, while odontoid abnormalities have not been reported. We report an odontoid anomaly in a girl with SMD-CF FN1-related showing the heterozygous variant c.505T>A; p.(Cys169Ser), presenting at 11.9 years of age with acute quadriparesis. Images showed spinal cord compression and injury associated with os odontoideum and C1-C2 instability. She required decompression and instrumented occipitocervical stabilization, suffering from residual paraparesis. This paper describes the first case of SMD-CF FN1-related accompanied by odontoid anomalies.
Subject(s)
Fractures, Bone , Osteochondrodysplasias , Spinal Diseases , Female , Humans , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Osteochondrodysplasias/complications , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Fractures, Bone/complicationsABSTRACT
CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.
Subject(s)
Dwarfism , Joint Dislocations , Musculoskeletal Abnormalities , Osteochondrodysplasias , Humans , Joint Dislocations/diagnosis , Joint Dislocations/genetics , Mutation , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Sulfotransferases/geneticsABSTRACT
Marshall syndrome is an extremely rare genetic disorder usually diagnosed in infancy with a prevalence of <1 in 1 million. Based on the literature reviewed, this is the first case report to provide a longitudinal history of a child with Marshall syndrome (from birth to age 12.5 years). This longitudinal case report arose in part from desires of this child's parents to share the story of their early fears at her initial diagnosis and compare those to how well she has turned out.
Subject(s)
Cataract , Collagen Type XI/deficiency , Craniofacial Abnormalities , Hearing Loss, Sensorineural , Osteochondrodysplasias , Humans , Child , Female , Mutation , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Craniofacial Abnormalities/genetics , Hearing Loss, Sensorineural/genetics , SyndromeABSTRACT
BACKGROUND: Cantu syndrome is a rare and complex multisystem disorder characterized by hypertrichosis, facial dysmorphism, osteochondroplasia and cardiac abnormalities. With only 150 cases reported worldwide, Cantu syndrome is now gaining wider recognition due to molecular testing and a growing body of literature that further characterizes the syndrome and some of its most important features. Cardiovascular pathology previously described in the literature include cardiomegaly, pericardial effusion, vascular dilation and tortuosity, and other congenital heart defects. However, cardiovascular involvement is highly variable amongst individuals with Cantu syndrome. In some instances, it can be extensive and severe requiring surgical management and long term follow up. CASE PRESENTATION: Herein we report a case of a fourteen-year-old female who presented with worsening pericardial effusion of unknown etiology, and echocardiographic findings of concentric left ventricular hypertrophy, a mildly dilated aortic root and ascending aorta. Her medical history was notable for hemoptysis and an episode of pulmonary hemorrhage secondary to multiple aortopulmonary collaterals that were subsequently embolized in early childhood. She was initially managed with Ibuprofen and Colchicine but continued to worsen, and ultimately required a pericardial window for the management of refractory pericardial effusion. Imaging studies obtained on subsequent visits revealed multiple dilated and tortuous blood vessels in the head, neck, chest, and pelvis. A cardiomyopathy molecular studies panel was sent, and a pathogenic variant was identified in the ABCC9 gene, confirming the molecular diagnosis of autosomal dominant Cantu syndrome. CONCLUSIONS: Vascular anomalies and significant cardiac involvement are often present in Cantu syndrome, however there are currently no established screening recommendations or surveillance protocols in place. The triad of hypertrichosis, facial dysmorphism, and unexplained cardiovascular involvement in any patient should raise suspicion for Cantu syndrome and warrant further investigation. Initial cardiac evaluation and follow up should be indicated in any patient with a clinical and/or molecular diagnosis of Cantu syndrome. Furthermore, whole body imaging should be utilized to evaluate the extent of vascular involvement and dictate long term monitoring and care.
Subject(s)
Cardiovascular Abnormalities , Hypertrichosis , Osteochondrodysplasias , Pericardial Effusion , Vascular Malformations , Adolescent , Female , Humans , Cardiomegaly/complications , Cardiomegaly/genetics , Cardiomegaly/pathology , Hypertrichosis/diagnosis , Hypertrichosis/genetics , Hypertrichosis/pathology , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/etiologyABSTRACT
Background: Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA) caused by Exostosin-Like Glycosyltransferase 3 (EXTL3) biallelic mutations is a very rare syndrome with only 16 cases reported in the literature. Skeletal dysplasia, neurodevelopmental delay, immunodeficiency, liver, and kidney cysts are the most common findings of this syndrome. Case Presentation: Here, we report on a patient who exhibited a lethal phenotype with clinical characteristics of this syndrome and had a homozygous pathogenic mutation in EXTL3 gene. Conclusions: ISDNA should be kept in mind in the differential diagnosis of patients presenting with neuro-immuno-skeletal dysplasia phenotype.
Subject(s)
Immunologic Deficiency Syndromes , Osteochondrodysplasias , Humans , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Mutation , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/genetics , Phenotype , N-Acetylglucosaminyltransferases/geneticsABSTRACT
The Schwartz-Jampel syndrome (SJS, OMIM #255800) is an ultra-rare genetic disease characterized by myotonic manifestations combined with bone and cartilage abnormalities. Following an autosomal recessive mode of inheritance, its prevalence is more significant in highly-inbred areas. The unraveling of the HSPG2 gene encoding a protein of the basal lamina enabled a better nosological delineation of the syndrome. The diagnosis is usually strongly suspected at the clinical level and then confirmed by molecular biology. To date, the treatment remains essentially symptomatic.
Title: Le syndrome de Schwartz-Jampel. Abstract: Le syndrome de Schwartz-Jampel (SJS, OMIM #255800) est une affection génétique ultra-rare définie par des manifestations myotoniques et des anomalies ostéo-articulaires. Transmis selon un mode autosomique récessif, sa prévalence est plus élevée dans les zones de forte endogamie. La découverte du gène HSPG2 codant une protéine de la lame basale a permis de mieux en délimiter les contours nosologiques. Le diagnostic est généralement très fortement suspecté cliniquement puis confirmé en biologie moléculaire. Le traitement reste à ce jour essentiellement symptomatique.
Subject(s)
Osteochondrodysplasias , Humans , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Osteochondrodysplasias/drug therapy , Inheritance Patterns , MutationABSTRACT
BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare systemic disease characterized by short stature, proteinuria, and recurrent infections. Patients usually have spondyloepiphyseal dysplasia, and progressive steroid-resistant nephropathy that leads to kidney failure. However, their clinical course after kidney transplantation (KT) is not yet well known. Here, we present our experience with cases of SIOD treated at our institute. CASE PRESENTATION: Since 2014, three children have been diagnosed with nephropathy resulting from SIOD. They presented with proteinuria in the nephrotic range at 7, 5, and 3 years of age. Focal segmental glomerulosclerosis was confirmed and progressed to kidney failure approximately 2 years after proteinuria was detected. These patients underwent living-donor KT from their parents. After KT, Case 1 lost his graft within 7 months due to multi-organ failure caused by disseminated adenovirus infection and died. Case 2 experienced graft failure 5 years after KT due to acute rejection from poor compliance. In Case 3, the allograft was still functioning 6 years after KT with low-dose tacrolimus single medication (trough level < 5 ng/mL). Extra-renal manifestations progressed regardless of KT, namely, right renal vein thrombosis and pulmonary hypertension in Case 1, severe bilateral hip dysplasia and Moyamoya syndrome in Case 2, and neutropenia and thrombocytopenia in Case 3, in addition to recurrent infection. CONCLUSION: In SIOD patients, KT is complicated with recurrent infections due to their inherent immune dysfunction. Additionally, extra-renal symptoms may render the patients morbid despite the recovery of kidney function.