Musculocontractural Ehlers-Danlos syndrome (MC-EDS) is a rare entity worldwide with underlying pathogenic variant in the carbohydrate sulfotransferase 14 (CHST14) gene. Previous reports of the same entity from India were of two unrelated cases. Ours is the first report of two siblings in an Indian family with craniofacial dysmorphism and distal arthrogryposis with a clinical diagnosis of EDS, where an underlying pathogenic variant in CHST14 was detected by exome sequencing.

Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented.

BACKGROUND: Generalized joint hypermobility (GJH) can be the result of several hereditary connective tissue disorders, especially Ehlers-Danlos syndrome. Cerebrovascular manifestations are among the most common complications in this disorder, and understanding their extent can help better diagnosis and prevention of hazardous events. We investigated visual evoked potential (VEP) changes in patients with GJH and compared them with healthy individuals.
METHODS: Our case-control study included 90 patients who fulfilled the Beighton score (B score) for joint hypermobility and other 90 healthy participants. All of them went under VEP study, and the amplitude and latency of the evoked potential (P100) were compared to each other.
RESULTS: The Case group had significantly higher B score (7.18 ± 0.967 vs. 1.18 ± 0.712), P100 latency (110.23 ± 6.64 ms vs. 100.18 ± 4.273 ms), and amplitude (6.54 ± 1.26 mv vs. 6.50 ± 1.29 mv) compared with the Control group, but the difference was only significant regarding B score, and P100 latency (p-value <.0001). Moreover, both latency and amplitude of P100 had significantly positive correlations with the B score in the Case group (p-value <.0001), but such correlations were not found in the Control group (p-value = .059).
CONCLUSIONS: Our study could reveal VEP changes, especially significant P100 latency in GJH patients without previous neurologic or musculoskeletal disorders. Whether these changes are due to GJH itself or are predictive of inevitable neurologic disease or visual pathway involvement, particularly Multiple Sclerosis needs further investigation with longer follow-up periods.

BACKGROUND: Joint hypermobility (JH) represents the extreme of the normal range of motion or a condition for a group of genetically determined connective tissue disorders. Generalized joint hypermobility (GJH) is suspected when present in all four limbs and the axial skeleton, scored in prepubescent children and adolescents by a Beighton Score (BS) ≥ 6. Parameters are also used to identify GJH in hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs). The purpose of this study is to characterize children with JH based on the location of variables in the BS ≥ 6 and identify children with JH in the axial skeleton, upper limbs (ULs), and lower limbs (LLs) simultaneously.
METHODS: We analyzed 124 medical records of one- to nine-year-old children with JH by BS.
RESULTS: The characterization of GJH by combinations of the axial skeleton, ULs, and LLs simultaneously totaled 25.7%. BS = 6 and BS = 8 consisted of variables located in ULs and LLs. BS = 7 included the axial skeleton, ULs, and LLs. BS ≥ 6 represents the majority of the sample and predominantly girls.
CONCLUSIONS: BS ≥ 6 represents the majority of the sample and predominantly girls. Most characterized children with GJH present BS = 6 and BS = 8 with variables located only in ULs and LLs, a condition that does not imply the feature is generalized. In children, BS = 7 and BS = 9 characterize GJH by including the axial skeleton, ULs, and LLs. These results draw attention to the implications for defining the diagnosis of hEDS and HSDs.

This case report presents a 34-year-old male with Ehlers-Danlos syndrome, type 2 diabetes mellitus, aortic valve regurgitation, and aortic bulb aneurysm. Following spine surgery for thoracic-lumbar stabilization, the patient underwent assessment for aortic bulb aneurysm and aortic valve replacement surgeries. Five months post spinal surgery, a coronary computed tomography angiography was performed. The coronary computed tomography angiography revealed unique findings, including the absence of the left main coronary artery, right coronary artery dominance, ectopic origin of the left circumflex artery from the right sinus of the valsalva, a coronary-pulmonary arterial fistula originating from the right sinus of the valsalva, and an additional right pulmonary vein. The patient was qualified for surgical treatment for an aortic bulb aneurysm, was informed about the high surgical risk, and is awaiting surgery. This case underscores the rarity of Ehlers-Danlos syndrome coexisting with multiple coronary artery anomalies. The presence of a coronary-pulmonary arterial fistula further emphasizes the need for specialized patient monitoring when Ehlers-Danlos syndrome and coronary anomalies converge.

Mutations in the FKBP14 gene encoding the endoplasmic reticulum resident collagen-related proline isomerase FK506 binding protein 22 kDa (FKBP22) result in kyphoscoliotic Ehlers-Danlos Syndrome (EDS), which is characterized by a broad phenotypic outcome. A plausible explanation for this outcome is that FKBP22 participates in the biosynthesis of subsets of collagen types: FKBP22 selectively binds to collagens III, IV, VI, and X, but not to collagens I, II, V, and XI. However, these binding mechanisms have never been explored, and they may underpin EDS subtype heterogeneity. Here, we used collagen Toolkit peptide libraries to investigate binding specificity. We observed that FKBP22 binding was distributed along the collagen helix. Further, it (1) was higher on collagen III than collagen II peptides and it (2) was correlated with a positive peptide charge. These findings begin to elucidate the mechanism by which FKBP22 interacts with collagen.

The aim of this work was to investigate the relationship foot pain and foot disability have with HRQoL in groups of women with RA, SLE and EDS, in comparison with a control group. A cross-sectional study was carried out with females with one of these conditions and a control group. The SF-12 questionnaire was used to collect data about quality of life. The type of foot was classified according to the footprint and the foot posture index. A total of 156 patients and 47 controls participated in the study (N = 203). Neither pain nor foot posture were different between groups. The physical and mental components of SF-12 were worse in rheumatoid arthritis and Ehlers-Danlos syndrome patients, and the physical component was worse in systemic lupus erythematosus patients, compared to controls. A significant difference was also observed in the mental component between systemic lupus erythematosus and Ehlers-Danlos syndrome patients, the latter having the lowest values among the groups. We can conclude that women with rheumatoid arthritis, Ehlers-Danlos syndrome, systemic lupus erythematosus and foot pain perceive a worse quality of life. There are no significant changes in foot posture. Pain and health-related quality of life are independent of foot posture.

Spinal deformity in Ehlers-Danlos syndrome (EDS) is an important symptom that can lead to trunk balance deterioration, respiratory dysfunction, and digestive disorders as the deformity progresses, thereby reducing a patient\'s quality of life and activities of daily living. The severity of the deformity varies widely, with treatment depending on the extent and the presence of associated complications. The present review addressed the current state of clinical research and treatment of spinal deformities in EDS with a specific focus on the musculocontractural type. Further studies are needed to better understand the underlying mechanisms of spinal deformity in EDS.

Cardiac valvular Ehlers-Danlos syndrome (EDS) (type IV) is a rare subtype of the syndrome. The progressive and severe involvement of the heart valves is the principal characteristic of cardiovascular EDS, hence the necessity of the screening of patients with EDS for possible cardiovascular complications. We herein describe a 17-year-old male patient, with a known case of Ehlers-Danlos syndrome, who was referred to our center due to symptomatic severe mitral regurgitation. Echocardiography showed the flailing of the A3 scallop of the mitral valve (MV) and severe enlargement of the left ventricle and the left atrium with mild systolic dysfunction. A physical examination revealed joint hyperlaxity, skin hyperelasticity, and abdominal hernias. He was, therefore, scheduled for surgery. MV repair was performed via commissuroplasty and ring annuloplasty, with an acceptable saline test. After being weaned from cardiopulmonary bypass, the patient had mild mitral regurgitation, which escalated to moderate-to-severe mitral within minutes. Consequently, the MV was replaced with a bioprosthetic valve. The postoperative course was uneventful. Due to the high fragility of the MV, any resection and sewing of its fragile leaflets may produce residual regurgitation and necessitate valve replacement. MV replacement may be more logical in such patients. Our patient\'s postoperative course was uneventful, and he was discharged without symptoms. Over 1 and 3 months of follow-up, he remained asymptomatic, and transthoracic echocardiography showed a normal bioprosthetic MV without paravalvular leakage.