The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes ZNF469 and PRDM5 each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated ZNF469 and PRDM5 on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes\' development of aneurysmal and dissection diseases.

BACKGROUND: Characteristics, practice patterns, and clinical outcomes of secondary spontaneous pneumothorax (SSP) with heritable connective tissue disorders (Marfan, Ehlers-Danlos, and Birt-Hogg-Dubé syndromes) are unclear.
METHODS: A nationwide Japanese inpatient database, which included data on 524 patients with SSP (884 hospitalizations) and 137821 with primary spontaneous pneumothorax (PSP) between July 2010 and March 2020, was used in this study. Hospitalization for SSP (n=884) was categorized into surgical (n=459) and non-surgical (n=425) groups, and the patient characteristics, treatment, and outcomes were compared between the groups. Multivariable analyses were performed to evaluate risk factors for pneumothorax recurrence. We also compared the patient characteristics among those with different underlying heritable connective tissue disorders.
RESULTS: Compared to the non-surgical group, the surgical group had less frequent readmission for pneumothorax (26% vs. 44%; hazard ratio, 0.47; 95% confidence interval, 0.38-0.58). Young patients (hazard ratio, 2.46; 95% confidence interval, 1.83-3.32) or those with Birt-Hogg-Dubé syndrome (2.53; 1.77-3.63) had a high risk of recurrence. Pneumothorax occurred frequently in teenagers with Marfan syndrome, in those aged 20-39 years with Ehlers-Danlos syndrome, and in those aged ≥40 years with Birt-Hogg-Dubé syndrome.
CONCLUSIONS: Detailed information on the characteristics and clinical course of SSP in heritable connective tissue disorders will aid the clinical decision-making process.

BACKGROUND: Patients with uncommon genetic conditions often face limited in-person resources for social and informational support. Hypermobile Ehlers-Danlos syndrome (hEDS) is a rare or underdiagnosed hereditary disorder of the connective tissue, and like those with similar diseases, patients with hEDS have begun to turn to social media in search of care and community. The aims of our study were to understand the usage habits and perceptions of utility of social media use for patients with hEDS in order to formulate suggestions for how clinicians may best engage these and similar patient populations about this topic.
METHODS: We conducted both a quantitative survey and qualitative interviews with patients who had received a robust clinical diagnosis of hEDS.
RESULTS: Twenty-four individuals completed the initial survey, and a subset of 21 of those participants completed an interview. Through thematic analysis, we identified four primary themes related to their experience with social media: (1) befriending others with their disease, (2) seeking and vetting information, (3) the risks and downsides of social media use, and (4) the desire for clinicians to discuss this topic with them.
CONCLUSIONS: We conclude by proposing five suggestions that emerge empirically from our data. These proposals will help clinicians engage their patients regarding social media use in order to promote its potential benefits and circumvent its potential harms as they pursue support for their hereditary condition.

UNASSIGNED: Patellar instability is frequently encountered in patients with Ehlers-Danlos syndrome (EDS). The clinical outcomes of isolated medial patellofemoral ligament reconstruction (MPFLR) for patellar instability in patients with EDS are unknown.
UNASSIGNED: To evaluate midterm clinical outcomes of isolated MPFLR for patellar instability in patients with EDS and factors affecting these outcomes.
UNASSIGNED: Case series; Level of evidence, 4.
UNASSIGNED: In a retrospective study, 31 patients (n = 47 knees) with EDS and patellar instability who underwent isolated MPFLR for recurrent patellar instability between 2008 and 2017 and had a minimum 2-year follow-up were identified. Preoperative radiographic images were measured for anatomic risk factors. Clinical outcomes-including postoperative complications-were evaluated. Factors associated with MPFLR failure were identified. Postoperative patient-reported outcomes (PROs)-including the pediatric version of the International Knee Documentation Committee, the Kujala score, the Hospital for Special Surgery Pediatric Functional Activity Brief Scale, the Banff Patellofemoral Instability Instrument 2.0, and the Knee injury and Osteoarthritis Outcome Score-were collected, and factors affecting PRO scores were analyzed.
UNASSIGNED: The mean age of the cohort was 14.9 ± 2 years. At a mean follow-up of 7.2 years, 18 of 47 (38.3%) knees required reoperations, of which 9 of 47 (19.1%) knees required revision stabilization for recurrent patellar instability. Also, 7 of 31 knees (22.6%) with autografts failed compared with 2 of 16 (12.5%) with allografts (P = .69). For autografts, 6 of 17 (35.3%) failures occurred with gracilis, but 0 of 13 (0%) occurred with semitendinosus (P = .02). Compared with patients without failures, patients with failed primary MPFLR were significantly younger (P = .0005) and were able to touch the palm to the floor with their knees extended (P = .03). For radiographic parameters, the patellar height and tilt were significantly higher in the failure group. The postoperative PROs were suboptimal at a mean follow-up of 5.2 years. All but 1 patient were satisfied with the final outcome.
UNASSIGNED: At the midterm follow-up, 38.3% of patients with EDS required further surgery after isolated MPFLR for patellar instability; half of these revisions (19.1%) were to address recurrent instability. Recurrent instability after isolated MPFLR was more likely in younger patients and those who could touch the palm to the floor with their knees extended. Postoperative PROs were inferior; nonetheless, patient satisfaction was high.

Ehlers-Danlos syndrome is a group of connective tissue disorders with 14 subtypes, involving joint hyperlaxity, tissue fragility, hypertensive skin and other systemic organs with an incidence of 1 in 1 000 000 worldwide. We report a middle childhood female born of second degree consanguineous marriage with limping gait with muscle weakness, with normal development and IQ. Examination revealed microcornea, distal joint laxity of fingers and wrist, hypotonia and broad-based limping gait. Fracture dislocation right hip was managed by fixation. With the atypical neuroimaging finding of cerebellar vermis hypoplasia, exome sequencing was ordered and confirmed as Ehlers-Danlos syndrome (musculocontractural type-1). Hence, genetic counselling was done and prognosis of the child was explained.

Spontaneous coronary artery dissection (SCAD) is an atypical cause of myocardial infarction, predominantly seen in women. Among various predisposing factors, genetic vasculopathies such as connective tissue diseases significantly contribute to SCAD. This report discusses a 36-year-old male diagnosed with vascular type Ehlers-Danlos syndrome following an anterior myocardial infarction and explores relevant literature.

UNASSIGNED: Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders (HSD) are associated with impairments in balance and physical function. However, the psychometric properties of relevant outcome measures remain largely unexplored. The objectives of this study were to evaluate the construct validity of the Mini-Balance Evaluation Systems Test (Mini-BESTest) alongside the test-retest reliability of the Mini-BESTest, Six Minute Walk Test (6MWT), and Lower Extremity Functional Scale (LEFS) in patients with the hypermobility subtype of EDS (hEDS) and HSD.
UNASSIGNED: Participants with hEDS/HSD (n = 20) attended two visits scheduled one to two weeks apart. The construct validity of the Mini-BESTest was determined through Pearson correlations between force plate balance measures, 6MWT, and LEFS. Test-retest reliability of the measures was evaluated through intraclass correlation coefficients (ICC). Minimal detectable change values with 95% confidence (MDC95) were also calculated.
UNASSIGNED: Mini-BESTest demonstrated significant correlations with force plate measures, 6MWT, and LEFS (r = -0.41 to 0.66). Test-retest reliability was excellent for the Mini-BESTest, 6MWT, and LEFS (ICC = 0.91 to 0.96). MDC95 was 4 for the Mini-BESTest, 77 m for the 6MWT, and 11 for the LEFS.
UNASSIGNED: The Mini-BESTest is valid and reliable for assessing balance and mobility in patients with hEDS/HSD.IMPLICATIONS FOR REHABILITATIONThe Mini Balance Evaluation Systems Test (Mini-BESTest) is valid in capturing aspects of balance and physical function in patients with hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorders.However, the Mini-BESTest may show a potential ceiling effect for high functioning patients in this population.The Mini-BESTest, 6 Minute Walk Test, and the Lower Extremity Functional Scale also show excellent test-retest reliability in this population.The Minimal Detectable Change with 95% confidence intervals is 4 for the Mini-BESTest, 77 m for the 6 Minute Walk Test, and 11 for the Lower Extremity Functional Scale in this population.

[This corrects the article DOI: 10.3389/fresc.2024.1280582.].

A female patient, known to have hypermobile Ehlers-Danlos syndrome (hEDS), underwent several elective gastroscopies under sedation in different hospitals. Except for a single incident of mild laryngospasm during emergence, all procedures were uneventful. On that occasion, following the procedure in the postanesthesia care unit, the patient suffered severe airway obstruction, and standard airway rescue techniques exacerbated adequate ventilation. After the removal of all stimuli and maintaining only an indirect oxygen supply via a mask in front of her face, her airway improved, and the patient fully recovered after 17 minutes. After the gastroscopy, physical examination revealed that the patient had an extremely flexible trachea that could be completely moved outside the midline to the extreme right and left. For the subsequent procedures, an airway plan was developed in conjunction with the patient and resulted in uncomplicated perianesthetic care. This case report serves to alert readers to the risk of adverse airway events in patients with EDS and suggests an alternative approach to avoid such complications. When patients receive care in different hospitals, adequate documentation is essential and adequate preoperative assessment is crucial. This case study demonstrates the value of patient-coproduction care plans.

BACKGROUND: There is limited understanding of the hypothesized association between the Ehlers-Danlos Syndromes (EDS), hypermobility and fractures in children. Despite this, EDS and hypermobility continue to be raised in the legal setting as possible causes of unexplained fractures in infants where there is a concern for physical abuse. Further understanding is needed regarding fractures in children with EDS and hypermobility.
OBJECTIVE: This study assessed fracture prevalence and characteristics in children diagnosed with EDS and Generalized Joint Hypermobility (GJH). The secondary outcome was fracture prevalence in infants <1 year of age.
METHODS: Children aged <18 years with EDS or GJH seen in a single-center EDS clinic from April 2017 to December 2021 were included. Diagnoses were based on the 2017 international classification. Exclusion criteria were concurrent medical conditions associated with bone fragility.
METHODS: This retrospective descriptive study examined variables including fracture history, fracture location, fracture type, age of sustaining fracture, and injury mechanism. Descriptive statistics were used for analysis.
RESULTS: Fracture prevalence was 34.6 % (9/26, 95 % CI [16.3, 52.9]) in the EDS population and 25.4 % (15/59, 95 % CI [14.3, 36.5]) in the GJH population. No fractures occurred in infancy. Most fractures occurred in the limbs. There were no rib or skull fractures. Most fractures were the result of an identifiable injury event.
CONCLUSIONS: In a cohort of children with formally diagnosed EDS or GJH, fractures occurred commonly in ambulatory children and generally in the limbs from identifiable events. This study does not support EDS or GJH as a cause of fractures in infancy.