Clinical Characteristics and Genetic Analysis of Birt-Hogg-Dubé Syndrome With Congenital Contractural Arachnodactyly in a Family

Background Birt-Hogg-Dubé Syndrome (BHD syndrome) and congenital contractural arachnodactyly (CCA) or Beals Hecht Syndrome (BHS) are clinically rare autosomal dominant genetic diseases. In this study, we find an extremely rare family with BHD Syndrome with CCA.Objective To investigate the clinical and genetic variation characteristics of a family with BHD Syndrome with CCA.Methods The patient was examined for chest Computed Tomography (CT), abdominal and heart color ultrasound, rheumatism immune-related indexes, and hand Direct Digital Radiography (DR), and Whole Exome Sequencing (WES) was performed on family members.Results The proband, male, developed symptoms of chest tightness and shortness of breath, accompanied by irritant cough 2 years ago, and then repeated spontaneous pneumothorax four times. Chest CT showed: spontaneous pneumothorax on the right side, emphysema in both lungs, and bullae in both lungs. No manifestations of kidney tumors and skin lesions. His son had a history of pulmonary bullobes and occurred spontaneous pneumothorax twice. He, his mother, and his son were all born with a hand deformity. Sequencing results showed that both the proband and his son were folliculin (FLCN) gene c.1015C>T（p.Gln339Ter） heterozygous variation, Fibrillin 2 gene (FBN2) gene c.3485G>A（p.Cys1162Tyr） heterozygous variation, associated with BHD syndrome and CCA.Conclusion For patients with chest tightness, shortness of breath, recurrent spontaneous pneumothorax, and congenital hand deformity without inducement, genetic testing should be carried out as soon as possible to make a clear diagnosis, which can guide treatment and genetic counseling.

Rare concurrent ocular myasthenia gravis and Graves’ ophthalmopathy in a man with Poland syndrome: a case report

Background Ocular myasthenia gravis and Graves’ ophthalmopathy are autoimmune diseases that are mediated by membrane receptors and share many identical clinical processes. Poland syndrome is a rare congenital deformity characterized by defects of the ipsilateral hand and the chest wall, and it is usually associated with hypoplasia of ipsilateral pectoral muscles and homolateral breast. However, to the best of our knowledge, the co-occurrence of these diseases has never been reported. In this study, we present a man with Poland syndrome who was diagnosed with Graves’ ophthalmopathy and ocular myasthenia gravis in succession. Case presentation A 43-year-old man presented with bilateral upper eyelid ptosis, bilateral eye protrusion, bilateral eye movement disorder and malformation of the right hand. Asymmetrical malformation of the chest wall and ipsilateral hand deformity were shown as Poland syndrome. He was diagnosed with ocular myasthenia gravis and Graves’ ophthalmopathy on the basis of clinical manifestations and laboratory examinations, including bilateral exophthalmos and progressive asymmetrical ophthalmoparesis without pupillary dysfunction, positive autoantibody tests, repetitive nerve stimulation tests, and computed tomography scans. Treatments with pyridostigmine bromide, thymectomy, and prednisone led to partial clinical improvement. After 13 months of follow-up, the symptoms of drooping eyelids were partially improved, but the eyeball protrusion and right hand deformity remained unchanged. Conclusions We report the first case of co-occurrence of ocular myasthenia gravis, Graves’ ophthalmopathy, and Poland syndrome. Genetic predisposition and immune dysregulation might be the pathogenesis of the association.

AB0228 COMPREHENSIVE RHEUMATOID HAND ASSESSMENT THROUGH PATTERN OF DEFORMITIES USING CLUSTER ANALYSIS

Background:The treatment of rheumatoid hand, which is characterized by thumb deformity, finger deformities, and ulnar drift (UD), is challenging. Its pathophysiology is complex, and a comprehensive understanding of the optimal intervention for this condition requires high technical skill and extensive clinical experience. Moreover, the natural course of rheumatoid hand itself remains unclear.Objectives:This study was performed to comprehensively evaluate rheumatoid hand through the specific parameters of each deformity.Methods:A rheumatoid hand cohort was established in 2004. In total, 134 hands of 67 patients were registered and underwent clinical evaluations. All hands surgically treated during follow-up were excluded from the study, but the contralateral hands were assessed. Evaluations were repeated in 2009 (100 hands of 52 patients) and in 2015 (63 hands of 37 patients) among all available patients. Therefore, among the data obtained from the 3 study endpoints, 297 hands were available for the cross-sectional analysis and 43 hands were available for the longitudinal analysis.Thumb deformities and finger deformities (swan-neck and boutonnière) were semi-quantitated by the Nalebuff classification score, and UD was quantified using a metacarpophalangeal joint condition scoring method1). A two-step cluster analysis was performed with entered parameters, and the distribution of each parameter was considered to clarify the characteristics of each cluster. The hands with different clusters at each endpoint were recruited for the following longitudinal analysis. The natural course of rheumatoid hand was considered based on the cluster change.Results:Seven clusters were used in this study to emphasize the impact of thumb deformity on function. The characteristics of each cluster were as follows. Cluster 1: mild finger deformities and various severities of UD; Cluster 2: type 1 thumb deformity and various severities of UD; Cluster 3: type 2 thumb deformity and severe UD; Cluster 4: type 3 or 4 thumb deformity, low or moderate level of swan-neck deformity, and various severities of UD; Cluster 5: various types of thumb deformity, severe boutonnière deformity, and various severities of UD; Cluster 6: type 1 thumb deformity, severe swan-neck deformity, and various severities of UD; and Cluster 7: type 6 thumb deformity.The longitudinal analysis showed that Cluster 1 mainly changed to Cluster 2 or 4, indicating progression of thumb deformity. Cluster 2 changed to Cluster 3, indicating that thumb type 1 progressed to type 2 (Figure 1). When the affected period was shorter than 10 years, the incidence of severe hand deformity (including two or more affected joint areas and low hand function) was <10%. In contrast, when the affected period was longer than 10 years, the incidence of severe hand deformity was >30% (Figure 2).Figure 1.Figure 2.Conclusion:This study suggests the presence of seven patterns of deformity enabling a comprehensive understanding of rheumatoid hand. Furthermore, the results of the longitudinal analysis suggest a natural course of rheumatoid hand progression. Therefore, from the distribution of parameters of each deformity and its severity, rheumatologists can easily classify rheumatoid hand and determine its pathophysiology to choose the most effective intervention.References:[1]Toyama S, Oda R, Tokunaga D et al. A new assessment tool for ulnar drift in patients with rheumatoid arthritis using pathophysiological parameters of the metacarpophalangeal joint. Modern rheumatology 2019, 29: 113-8.Acknowledgments:This work was supported by JSPS KAKENHI Grant Numbers JP19K19914.Disclosure of Interests:None declared