Impact of joint hypermobility syndrome on gastric accommodation and nutrient tolerance in functional dyspepsia.

Functional dyspepsia (FD) is defined as the presence of gastroduodenal symptoms in the absence of organic disease that is likely to explain the symptoms. Joint hypermobility (JH) refers to the increased passive or active movement of a joint beyond its normal range and is characteristically present in patients with joint hypermobility syndrome (JHS), which is a hypermobile subtype of Ehlers-Danlos syndrome (EDS). Recent reports have highlighted the co-existence of FD with Ehlers-Danlos syndrome. Our aim was to study the prevalence of JHS in FD compared with healthy subjects and to study the impact of co-existing JHS on gastric motility, nutrient tolerance, and dyspeptic symptoms in FD. METHODS: FD patients filled out a dyspepsia symptom severity score. Intragastric pressure (IGP) was measured with high-resolution manometry (HRM) during the intragastric infusion of nutrition drink (ND, 1.5 Kcal/ml, 60 ml/min) until maximal satiation in healthy subjects and FD. We compared IGP profiles and nutrient tolerance in HS and FD with or without JHS. RESULTS: JHS was present in 54% of FD patients (n = 39, 41.2 ± 2.2 years old) and 7% of healthy subjects (n = 15, 27.3 ± 2.3 years old). IGP drop and nutrient tolerance were lower in non-JHS-FD compared with JHS-FD and HS (AUC JHS-FD: -17.9 ± 2.5 vs. non-JHS-FD: -13.0 ± 3.3 mmHg min, p = 0.2, HS:-19.6 ± 2.9 mmHg min; ND tolerance non-JHS-FD: 671.0 ± 96.0 vs. JHS-FD: 842.7 ± 105.7 Kcal, p = 0.25, HS: 980.0 ± 108.1 Kcal). CONCLUSION: JHS often co-exists with FD. Non-JHS-FD was characterized by decreased accommodation and lower nutrient tolerance characterized compared with JHS-FD. Clinicaltrials.gov, reference number NCT04279990.

Two-Stage Approach for Unstable Pediatric Craniocervical Junction Anomalies with a Halo Vest and Delayed Occipitocervical Fusion: Technical Note, Case Series, and Literature Review.

OBJECTIVE: Malformations in the craniocervical junction (CCJ) are rare in the pediatric population but often need surgical treatment. We present a pediatric case series of patients treated with a 2-stage surgical approach with a halo vest and occipitocervical fusion and review complications and outcomes. METHODS: A retrospective analysis of a single-center case series was performed. Pediatric patients affected by congenital craniocervical junction anomalies and treated with a 2-stage approach were included. A halo vest was implanted in the first surgery, and ambulatory progressive reduction was performed. When a favorable anatomic situation was observed, arthrodesis was performed. Safety analysis was undertaken by analyzing the incidence of complications in both procedures. Effectivity analysis was carried out analyzing radiologic and clinical outcome (Goel grade and modified Japanese Orthopaedic Association score). Student t test was used for statistical analysis. RESULTS: Sixteen cases were included. Mean age of patients was 9.38 years. Safety analysis showed 2 halo loosenings, 1 pin infection, 2 wound infections, 1 cerebrospinal fluid leak, and 2 delayed broken rods. No major complications were observed. Radiologic analysis showed an improvement in the tip of the odontoid process to the McRae line distance (from -3.26 mm to -6.16 mm), atlantodental interval (from 3.05 mm to 1.88 mm), clival-canal angle (from 134.61° to 144.38°), and cervical kyphosis (from 6.39° to 1.54°). Clinical analysis also showed improvement in mean Goel grade (from 1.75 to 1.44) and modified Japanese Orthopaedic Association score (from 15.12 to 16.41). CONCLUSIONS: The 2-stage approach was a suitable and effective treatment for craniocervical junction anomalies in pediatric patients.

Case report of a PRDM5 linked brittle cornea syndrome type 2 in association with a novel SLC6A5 mutation.

A 3-year-old girl presenting with blue sclera, hyperlaxity and developmental dysplasia of hip was found to have bilateral corneal thinning with astigmatism and keratoconus. By clinical exome sequencing, a frameshift mutation c.713_716 del TTTG p.(Val238Alafs*35) in PRDM5 gene causing brittle cornea syndrome 2 and a novel frameshift mutation c.401dup p.(Ser135Glufs*53) in SLC6A5 gene causing Hyperekplexia 3 were identified. No features of hyperekplexia were identified in proband. The novel homozygous mutation of SLC6A5 gene in the proband was presently asymptomatic but they were apprised of the possibility of developing neurological symptoms in the later years.

Surgical Management of Shoulder and Knee Instability in Patients with Ehlers-Danlos Syndrome: Joint Hypermobility Syndrome.

Ehlers-Danlos Syndrome (EDS) is a hereditary disorder of the connective tissue, which has been classified into numerous subtypes over the years. EDS is generally characterized by hyperextensible skin, hypermobile joints, and tissue fragility. According to the 2017 International Classification of EDS, 13 subtypes of EDS have been recognized. The majority of genes involved in EDS are either collagen-encoding genes or genes encoding collagen-modifying enzymes. Orthopedic surgeons most commonly encounter patients with the hypermobile type EDS (hEDS), who present with signs and symptoms of hypermobility and/or instability in one or more joints. Patients with joint hypermobility syndrome (JHS) might also present with similar symptomatology. This article will focus on the surgical management of patients with knee or shoulder abnormalities related to hEDS/JHS.

Knee arthrodesis for a congenital luxation with Larsen syndrome.

A 31-year-old woman with known Larsen syndrome presented with congenital chronic luxation of her right knee with increasing instability symptoms, which limited her daily activities. We refrained from a constrained knee arthroplasty due to her relatively young age and decided to perform a knee arthrodesis. Knee arthrodesis is a viable lifelong-lasting operative treatment alternative for specific instability-related knee disease. The knee arthrodesis was performed by double plating with an additional fixation of the patella. At 1-yearfollow-up, she was able to walk without limitations and did not experience any pain with complete consolidation of the arthrodesis. At 2-year follow-up, she performed all her daily activities without limitations. Both the Knee injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee subjective knee form (IKDC) improved at 2-year follow-up (KOOS: 61.3; IKDC: 56.3) compared with 1-year follow-up (KOOS: 52; IKDC: 40.2).

Brittle cornea syndrome: Disease-causing mutations in ZNF469 and two novel variants identified in a patient followed for 26 years.

AIMS: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder. The aim of this study was to review ZNF469 mutations associated with BCS type 1 to date and to describe an additional case of Czech/Polish background. METHODS: Whole genome sequencing was undertaken to identify the molecular genetic cause of disease in the proband. Sequence variants in ZNF469 previously reported as BCS type 1-causing were searched in the literature, manually curated and aligned to the reference sequence NM_001127464.2. RESULTS: The proband has been reviewed since childhood with progressive myopia and hearing loss. Aged 13 years had been diagnosed with Stickler syndrome. Aged 16.5 years, he developed acute hydrops in the left eye managed by corneal transplantation. At the age of 26, he experienced right corneal rupture after blunt trauma, also managed by grafting. He had a number of secondary complications and despite regular follow-up and timely management, the right eye became totally blind and the left eye had light perception at the last follow-up visit, aged 42. He was found to be a compound heterozygote for two novel mutations c.1705C>T; p.(Gln569*) and c.1402_1411del; p.(Pro468Alafs*31) in ZNF469. In total 22 disease-causing variants in ZNF469 have been identified, mainly in consanguineous families or endogamous populations. Only four probands, including the case described in the current study, harboured compound heterozygous mutations. CONCLUSION: BCS occurs very rarely in outbred populations which may cause diagnostic errors due to poor awareness of the disease. Investigation into the underlying molecular genetic cause in patients with connective tissue disorders may lead to a re-evaluation of their clinical diagnosis.

The Managment of cervical spine abnormalities in children with spondyloepiphyseal dysplasia congenita: Observational study.

Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant disorder, characterized by disproportionate dwarfism with short spine, short neck associated with variable degrees of coxa vara. Cervical cord compression is the most hazardous skeletal deformity in patients with SEDC which requires special attention and management.Ten patients with the clinical and the radiographic phenotypes of spondyloepiphyseal dysplasia congenita have been recognized and the genotype was compatible with single base substitutions, deletions or duplication of part of the COL2A1 gene (6 patients out of ten have been sequenced). Cervical spine radiographs showed apparent atlantoaxial instability in correlation with odontoid hypoplasia or os-odontoideum.Instability of 8 mm or more and or the presence of symptoms of myelopathy were the main indications for surgery. Posterior cervical fusion from the occiput or C1-3, decompression of C1-2 and application of autorib transfer followed by halo vest immobilization have been applied accordingly.Orthopedic management of children with spondyloepiphyseal dysplasia congenita (SEDC) should begin with the cervical spine to avoid serious neurological deficits and or mortality.

Reconstruction of Symptomatic Congenital Anterior Cruciate Ligament Insufficiency.

BACKGROUND: Hypoplasia or congenital absence of the anterior cruciate ligament (ACL) is a rare disorder occurring in ∼1 in every 6000 births. Although some patients with hypoplasia or agenesis of the ACL may not complain of instability, others desire to participate in more demanding activities that require the stability of a competent ACL. There are limited reports of surgical treatment of this patient population. The purpose of this study was to report ACL reconstruction in a case series of patients with symptomatic congenital ACL deficiency. METHODS: A retrospective medical record review of the surgical treatment of 14 knees (13 patients) with congenital absence of the ACL at a tertiary care institution from 1995 to 2012 was performed. Patients with a minimum of 1 year of clinical follow-up were eligible for inclusion. RESULTS: The mean age at time of surgery was 12.6 (range, 3 to 22), including 6 patients <12 years of age. Mean follow-up was 2.9 years (range, 1 to 6.6). Nine of 13 patients (69%) had underlying congenital abnormalities/associated syndromes. Preoperative Lachman and pivot shift examination was International Knee Documentation Committee grade C or D in all but 1 knee. ACL reconstruction was performed with combined intra-articular/extra-articular physeal sparing reconstruction with iliotibial band (n=5), autograft hamstring (n=2) or bone-patellar tendon-bone (n=3), or allograft (n=4). Multiligament reconstruction of associated ligamentous deficiency was performed in 7 knees (50%). Postoperative Lachman and pivot shift testing was International Knee Documentation Committee (IKDC) grade A or B in all but 1 knee. One patient with congenital absence of multiple knee ligaments required revision ACL reconstruction surgery, with concurrent first-time posterior cruciate ligament reconstruction, due to persistent instability. None required revision surgery due to graft tear at a minimum of 1-year follow-up. CONCLUSIONS: Surgical stabilization of symptomatic congenital ACL insufficiency, with associated ligamentous reconstruction as required on a case-by-case basis, results in improved stability at early clinical follow-up, with low complication rates. LEVEL OF EVIDENCE: Level IV-retrospective case series.

Use of an onlay corneal lamellar graft for brittle cornea syndrome.

Brittle cornea syndrome (BCS1 OMIM #229200, BCS2 #614170) is a rare autosomal recessive condition characterised by diffuse thinning and fragility of the cornea. Affected individuals are at risk of globe rupture and blindness after relatively minor eye trauma. We describe a 9-year-old girl with BCS1, already blind in one eye following trauma, who had a 14 mm diameter corneoscleral onlay graft to her contralateral eye to reduce gross irregular corneal astigmatism and potentially to reduce further risk from accidental injury. Although there was a significant initial improvement in the unaided visual acuity, there was subsequent visual loss from secondary glaucoma. In addition, despite the onlay graft, an acute corneal hydrops developed approximately 2 years following surgery, suggesting that in BCS1, corneal tissue degeneration or resorption continues despite external support. Finally, because secondary glaucoma is not a feature of BCS1, we speculate that the onlay graft may have reduced aqueous outflow by compression of the thinned sclera.

Hip Instability in Patients With Down Syndrome.

The incidence of hip instability in children with Down syndrome is 1% to 7%. The natural history is often progressive, with the typical onset of hypermobility of the hip evolving to habitual dislocation, persistent subluxation, and fixed dislocation, and eventually leading to the loss of independent mobility. Treatment focuses on stabilizing the hip joint and depends on the patient's age and the severity of the disease. Typically, surgical intervention is recommended for the treatment of patients with habitual dislocation, subluxation, and complete dislocation of the hip. When indicated, surgical management must take into account associated anatomic abnormalities of the femur and acetabulum. Hip instability in Down syndrome may persist despite surgical intervention and remains a difficult condition to manage.

Focal linear elastosis in a patient with joint hypermobility syndrome.

Focal linear elastosis (FLE) is a benign skin findingcharacterized by hypertrophic linear plaques withabnormal elastic fibers on histology. We present aunique case in which focal linear elastosis occurredin the setting of joint hypermobility syndrome(JHS). Our patient, a 20-year-old man with a medicalhistory significant for symptoms consistent with JHS,had been followed by the rheumatology clinic formany months. He was referred to the dermatologydepartment for further evaluation of asymptomaticlongitudinal bands on his back that had been presentfor many years. He denied trauma but endorsed ahistory of 'stretch marks.' On examination there werenumerous horizontally oriented, firm, linear, yellowto flesh colored bands, all non-tender to palpation.Punch biopsies were performed of involved anduninvolved skin. Histopathology of normal skinrevealed no significant abnormalities whereasinvolved skin demonstrated broadened collagenbundles in the deep dermis. The elastic fiber stain,Verhoeff-Van Gieson, revealed a gross increase in thenumber of elastic fibers, fragmented fibers, fiberswith "paintbrush" or widened-ends, fibers of varyingthickness, and clumped fibers. This combination ofhistopathologic and clinical features was consistent with FLE.

Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome.

INTRODUCTION: An increased risk of preterm birth in women with joint hypermobility syndrome or Ehlers-Danlos syndrome is suspected. MATERIAL AND METHODS: In this nationwide cohort study from 1997 through 2011, women with either joint hypermobility syndrome or Ehlers-Danlos syndrome or both disorders were identified through the Swedish Patient Register, and linked to the Medical Birth Register. Thereby, 314 singleton births to women with joint hypermobility syndrome/Ehlers-Danlos syndrome before delivery were identified. These births were compared with 1 247 864 singleton births to women without a diagnosis of joint hypermobility syndrome/Ehlers-Danlos syndrome. We used logistic regression, adjusted for maternal age, smoking, parity, and year of birth, to calculate adjusted odds ratios for adverse pregnancy outcomes. RESULTS: Maternal joint hypermobility syndrome/Ehlers-Danlos syndrome was not associated with any of our outcomes: preterm birth (adjusted odds ratio = 0.6, 95% confidence interval 0.3-1.2), preterm premature rupture of membranes (adjusted odds ratio = 0.8; 95% confidence interval 0.3-2.2), cesarean section (adjusted odds ratio = 0.9, 95% confidence interval 0.7-1.2), stillbirth (adjusted odds ratio = 1.1, 95% confidence interval 0.2-7.9), low Apgar score (adjusted odds ratio = 1.6, 95% confidence interval 0.7-3.6), small for gestational age (adjusted odds ratio = 0.9, 95% confidence interval 0.4-1.8) or large for gestational age (adjusted odds ratio = 1.2, 95% confidence interval 0.6-2.1). Examining only women with Ehlers-Danlos syndrome (n = 62), we found a higher risk of induction of labor (adjusted odds ratio = 2.6; 95% confidence interval 1.4-4.6) and amniotomy (adjusted odds ratio = 3.8; 95% confidence interval 2.0-7.1). No excess risks for adverse pregnancy outcome were seen in joint hypermobility syndrome. CONCLUSION: Women with joint hypermobility syndrome/Ehlers-Danlos syndrome do not seem to be at increased risk of adverse pregnancy outcome.

Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

BACKGROUND: Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. METHODS: In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. RESULTS: Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. CONCLUSIONS: While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain.

Arthralgias, fatigue, paresthesias and visceral pain: can joint hypermobility solve the puzzle? A case report.

BACKGROUND: Joint hypermobility syndrome describes a disorder in which musculoskeletal pain occurs in a generalized joint hypermobility substrate. The clinical picture comprises variable manifestations which involve mainly but not exclusively the musculoskeletal system, and evolve over the person's lifetime. CASE PRESENTATION: Describing the case of a 20-year-old female with generalized arthro-myalgias, persistent fatigue and troublesome visceral pain, we illustrate how a frequently ignored clinical sign such as joint hypermobility can be the keystone to clarify different simultaneous symptoms. All of the patient's physical complaints had been investigated separately during her previous medical examinations, and several tests repeatedly gave negative results. The patient received different diagnoses that describe only part of her problems, such as irritable bowel syndrome for visceral pain, fibromyalgia for arthralgias or depression for fatigue. These approaches gave rise to pharmacological or physical treatments which did not improve her quality of life in any way and in some instances worsened the situation. Pronounced joint hypermobility which led the patient to flex her joints excessively, causing subluxations in several districts, was the only sign overlooked. CONCLUSION: Exploring the patient's articular features in her clinical context led us to diagnose joint hypermobility syndrome, a complex and often ignored condition. The case highlights the utility of a multidisciplinary approach and coordinated interventions to define and manage this clinical entity.

United States Physical Therapists' Knowledge About Joint Hypermobility Syndrome Compared with Fibromyalgia and Rheumatoid Arthritis.

BACKGROUND: Joint hypermobility syndrome (JHS) is one of the most common inherited connective tissue disorders. It causes significant pain and disability for all age groups, ranging from developmental delay among children to widespread chronic pain in adults. Experts in JHS assert that the condition is under-recognized and poorly managed. PURPOSE: The aim of this study was to assess US physical therapists' knowledge about JHS compared with other causes of widespread pain and activity limitations: fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis. METHODS: Cross-sectional, Internet-based survey of randomly selected members of the American Physical Therapy Association and descriptive statistics were used to explore physical therapists' knowledge about JHS, fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis, and chi square was used to compare knowledge about the different conditions. RESULTS: The response rate was 15.5% (496). Although 36% recognized the Beighton Scale for assessing joint hypermobility, only 26.8% of respondents were familiar with the Brighton Criteria for diagnosing JHS. Few respondents (11-19%) realized that JHS has extra-articular features such as anxiety disorder, fatigue, headache, delayed motor development, easy bruising and sleep disturbance. Physical therapists working in environments most likely to see patients with JHS underestimated the likely prevalence in their patient population. CONCLUSIONS: The results suggest that many physical therapists in the United States are not familiar with the diagnostic criteria, prevalence or common clinical presentation of JHS.

Corneal Cross-Linking for Brittle Cornea Syndrome.

PURPOSE: To describe corneal cross-linking (CXL) as a treatment option for brittle cornea syndrome (BCS). METHODS: Case report. RESULTS: Ethical decision making enabled bilateral sequential transepithelial CXL in an 11-year-old girl with BCS. Postoperative courses were uneventful with a bilateral stromal demarcation line, unchanged corneal transparency, constant endothelial cell density, and stable topography 2 years after intervention. CONCLUSIONS: Modified CXL can safely be performed in patients with BCS. Ethical review may be helpful for interventions deviating from standard practice.

Congenital Absence of the Anterior Cruciate Ligament.

The incidence of congenital absence of the anterior cruciate ligament (ACL) is extremely low. Congenital ACL absence has most often been found in association with conditions such as knee dislocation, knee dysplasia, proximal focal femoral deficiency, and fibular hemimelia. We report on the incidental finding of ACL aplasia in a patient with a medial meniscal tear and history of leg-length discrepancy. As has been found in prior case studies, this patient had hypertrophy of the meniscofemoral ligament of Humphrey, which likely lent her stability. This case highlights the importance of differentiating between a stable and an unstable knee in congenital absence of the ACL.

Mapping of the femoral trochlea in a newborn population: an ultrasonographic study.

BACKGROUND: The anatomy of the femoral trochlea is of vital importance to the stability of the patellofemoral joint. Knowing the characteristics of the femoral trochlea in newborns might prove useful when considering the predisposing factors to patellar instability. PURPOSE: To define the normal anatomy and the natural variances of the femoral trochlea in a newborn population as well as evaluation of ultrasonography as a method of imaging. MATERIAL AND METHODS: The femoral trochlea of both knees of 174 newborns (82 girls and 92 boys) was examined using ultrasonography within 3 days after birth. For evaluation of the repeatability of the method, a separate population of 40 newborns was examined by two examiners. RESULTS: The sulcus angle (SA) and Trochlear Index (TI) proved to be the most reliable and reproducible parameters. The overall mean SA was 148° (SD 5.6). An angle of more than 159° was defined as dysplastic, and 17 of the knees were categorized in this group. The overall mean TI was 2.21 (SD 0.05). A value of less than 2.11 was defined as dysplastic and 11 of the newborns fell into this category. CONCLUSION: As a method of visualizing the newborn femoral trochlea and the position of the patella, ultrasonography is a reliable tool and might be of vital importance. In a further perspective, knowledge of the anatomy of a normal versus a dysplastic newborn trochlea renders it possible to study the predisposing factors to patellar instability and methods of treatment. Our results indicate that dysplasia of the femoral trochlea may be congenital.

Patellofemoral ligament reconstruction in a patient with Rubinstein-Taybi syndrome.

Recurrent dislocation of patella may occur in patients with ligament laxity. Method of treatment in this condition is controversial but patellofemoral ligament reconstruction is the most accepted method. We present a patient with Rubinstein-Taybi syndrome and recurrent patellar dislocation who managed successfully by patellofemoral ligament reconstruction.

Hypermobility syndromes from the clinician's perspective: an overview.

Symptomatic generalized hypermobility is a frequent occurring condition among patients referred to the rheumatologist or other medical specialist. In a subset of patients, a further classifying diagnosis of a specific syndrome can (and should) be made, based on pattern recognition and knowledge of the spectrum of hypermobility syndromes. Diagnostic clues are the patient's and family history and signs at physical examination, including skin abnormalities. It is especially important to recognize hypermobility syndromes with potentially life threatening complications. Genetic testing is only available for some syndromes; is only indicated if there is a reasonable pretest probability regarding a specific syndrome, especially if this syndrome can have life-threatening complications. The therapy is for the major part of syndromes only symptomatic; key features of management are education and physical exercises; joint surgery is to be avoided.