| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:20847697 | PARTIAL | It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene. | This reference indicates that COL5A1-related EDS is a subset of classic EDS, making up about 50% of classic EDS cases. However, it does not provide specific global prevalence rates of COL5A1-related EDS. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:20847697 | PARTIAL | Classic Ehlers-Danlos syndrome is a heritable connective tissue disorder characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. | While the COL5A1-related Ehlers-Danlos Syndrome (classic type) is described as a heritable connective tissue disorder with certain clinical features observable from birth, the literature does not specifically detail the age range for the onset of symptoms as 'Birth-20'. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:9042913 | SUPPORT | The mutation causes the substitution of the most 5' cysteine residue by a serine within a highly conserved sequence of the pro(alpha)1(V) C-propeptide domain and causes reduction of collagen V by preventing incorporation of the mutant pro(alpha)1(V) chains in the collagen V trimers. | This reference describes how mutations in COL5A1 lead to defective synthesis and assembly of collagen type V, supporting the given statement. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:20847697 | SUPPORT | In the majority of patients with molecularly characterized classic Ehlers-Danlos syndrome, the disease is caused by a mutation leading to a nonfunctional COL5A1 allele and resulting in haploinsufficiency of type V collagen. | The literature indicates that mutations in the COL5A1 gene lead to abnormalities in collagen type V, resulting in weakened connective tissues. |
| PMID:15095409 | SUPPORT | EDS cells with COL5A1 haplo-insufficiency deposited less than one-half of hydroxyproline as collagen compared to control fibroblasts. This deficit in type V collagen was associated with the assembly of significantly fewer fibrils compared to control. | This study demonstrates that reduced type V collagen results in weaker connective tissue due to a significant decrease in collagen fibril assembly. |
| PMID:12836217 | SUPPORT | The classical form of the syndrome, which will be principally discussed in this review, can be due to mutations on collagen V, a fibrillar collagen present in small amounts in affected tissues. | The literature describes the role of collagen V and its mutations in causing connective tissue fragility, therefore supporting the statement. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:19370768 | SUPPORT | Classical Ehlers-Danlos syndrome (EDS) is a heritable disorder characterized by joint hypermobility, skin hyperextensibility, and abnormal wound healing. | The provided literature directly supports the claim that Ehlers-Danlos Syndrome, particularly related to COL5A1, results in fragile tissues leading to manifestations like joint dislocations, skin hyperextensibility, and poor wound healing. |
| PMID:19592142 | SUPPORT | The bleeding tendency is most prominent in the Ehlers-Danlos syndrome (EDS), a heterogeneous group of HDCT sharing clinical manifestations of fragility in skin, ligaments, blood vessels and internal organs. | The literature mentions fragility in tissues due to EDS, consistent with fragile tissues leading to manifestations such as joint dislocations and skin hyperextensibility. |
| PMID:20697718 | SUPPORT | Ehlers-Danlos Syndrome is a term that comprises a variety of inherited connective tissue disorders characterized primarily by skin hyperextensibility, joints hypermobility and excessive dislocations, easy bruisability, generalized fragility. | The literature supports the claim, highlighting tissue fragility, joint hypermobility, and skin hyperextensibility as key characteristics. |
| PMID:19055167 | SUPPORT | Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders characterized by hyperextensibility, delayed wound healing, joint hypermobility, thin skin, easy bruising, tissue fragility, 'cigarette-paper' scarring over bony prominences. | This reference supports the claim, describing characteristics that align with tissue fragility and symptoms such as joint dislocations, skin hyperextensibility, and poor wound healing. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:34807421 | SUPPORT | Currently, musculoskeletal manifestations related to joint hypermobility are perceived as the most prevalent determinants of the quality of life of affected individuals. | This reference supports the high frequency and significant impact of joint hypermobility in Ehlers-Danlos syndrome. |
| PMID:19370768 | SUPPORT | Classical Ehlers-Danlos syndrome (EDS) is a heritable disorder characterized by joint hypermobility, skin hyperextensibility, and abnormal wound healing. | The reference supports the musculoskeletal phenotype involving joint hypermobility and associated symptoms like joint pain. |
| PMID:35964930 | SUPPORT | Classical (cEDS) and vascular type (vEDS) are the most prevalent subtypes and are caused by heterozygous pathogenic variants in COL5A1, COL5A2, COL1A1 or, respectively, in COL3A1. | This indicates a direct relationship between COL5A1 mutations and the classical EDS phenotype, which includes musculoskeletal manifestations such as joint hypermobility. |
| PMID:10906878 | SUPPORT | Thirty patients with Type III Ehlers-Danlos syndrome reported joint pain more frequently than did patients with Types I, II, or IV. | This supports the involvement of recurrent joint dislocations and chronic joint pain in the EDS phenotype. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:20847697 | SUPPORT | Classic Ehlers-Danlos syndrome is a heritable connective tissue disorder characterized by skin hyperextensibility, fragile and soft skin... | The abstract clearly states that skin hyperextensibility is a primary feature of classic Ehlers-Danlos syndrome, which is often caused by COL5A1 mutations. |
| PMID:36764582 | SUPPORT | A high prevalence of skin hyperextensibility, bruising, and soft skin were noted. | Skin hyperextensibility is identified as a common feature in Ehlers-Danlos syndromes, supporting the statement. |
| PMID:37594181 | SUPPORT | The classic tragic facial expression was observed as well as chronic pruritus and mild hyperesthesia. | This reference supports the dermatologic phenotype of Ehlers-Danlos Syndrome, including traits commonly associated with COL5A1 mutations. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:20847697 | SUPPORT | Classic Ehlers-Danlos syndrome is a heritable connective tissue disorder characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars. | The literature specifies that classic Ehlers-Danlos syndrome, which includes COL5A1-related cases, involves the formation of atrophic scars as a common dermatologic phenotype. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:20847697 | SUPPORT | Classic Ehlers-Danlos syndrome is a heritable connective tissue disorder characterized by ... easy bruising. | This reference confirms the presence of easy bruising as a common phenotype of classic Ehlers-Danlos syndrome, which is often related to COL5A1 mutations. |
| PMID:36764582 | SUPPORT | The Ehlers-Danlos syndromes (EDSs) comprise a group of connective tissue disorders that manifest with... easy bruising... | This source supports that easy bruising is a common dermatologic manifestation in Ehlers-Danlos syndromes, which includes types related to COL5A1 mutations. |
| PMID:15566352 | SUPPORT | Easy bruising is, to a variable degree, present in all subtypes of EDS... | This excerpt indicates that easy bruising is a common feature across various subtypes of Ehlers-Danlos syndrome, which would include the COL5A1-related types. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:21193204 | PARTIAL | Fifteen of the 252 patients (6.0%) had mitral valve prolapse (MVP), although only one patient (0.4%) had MVP that was mild to moderate. | The literature shows an occasional incidence of mitral valve prolapse in Ehlers-Danlos Syndrome, and while the exact subtype related to COL5A1 is not specified, it partially supports the statement. |
| PMID:34776077 | SUPPORT | The EDS are currently classified into thirteen subtypes. There is substantial symptoms overlap between the EDS subtypes, and they are associated with an increased incidence of cardiovascular abnormalities, such as mitral valve prolapse and aortic dissection. | This reference supports the association of Ehlers-Danlos Syndrome (a group including COL5A1-related subtypes) with mitral valve prolapse. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:26376608 | PARTIAL | Commonest GI symptoms were: abdominal pain (56.1%), nausea (42.3%), constipation (38.6%), heartburn (37.6%), and irritable bowel syndrome-like symptoms (27.5%)... Among 37.8% of the 378 patients who underwent esophagogastroduodenoscopy, the commonest abnormalities were gastritis, hiatal hernia and reflux esophagitis. | The study indicates that reflux esophagitis, which is related to gastroesophageal reflux, is one of the common abnormalities observed in EDS patients. However, it does not explicitly distinguish the frequency of this phenotype for COL5A1-related EDS specifically. |
| name | presence | evidence |
|---|---|---|
| Collagen Type V | Decreased or Abnormal | TRUNCATED |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:30858776 | SUPPORT | Among all tested patients, nine mutations of COL5A1 gene were detected (8 missense mutations and 1 splice site). | This reference confirms the existence of missense and splice site mutations in the COL5A1 gene among Ehlers-Danlos Syndrome patients. |
| PMID:33656776 | SUPPORT | Glycine substitution mutation of COL5A1 in classic Ehlers-Danlos syndrome: a case report and literature review. | This reference supports the presence of missense mutations specifically related to COL5A1 in Ehlers-Danlos Syndrome. |
| PMID:35241120 | PARTIAL | This study supports that rs12722 is associated with an elevated susceptibility to ligament injury, especially in the Caucasian population. | While the study primarily investigates the association of COL5A1 polymorphisms with musculoskeletal injuries, it partially supports the statement by recognizing relevant genetic variants. |
| PMID:2683783 | WRONG_STATEMENT | Mutations in the majority of the 20 known collagen genes have not yet been identified. | This reference doesn't support the existence of frameshift mutations in COL5A1, making the specific part of the statement regarding frameshift mutations unsubstantiated. |
| name |
|---|
| Autosomal Dominant |
| name | description |
|---|---|
| Missense Mutations | Single nucleotide changes resulting in altered amino acid sequence. |
| Splice Site Mutations | Changes affecting mRNA splicing and leading to exon skipping or intronic retention. |
| Frameshift Mutations | Insertions or deletions causing a shift in the reading frame and often resulting in a premature stop codon. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:26452443 | PARTIAL | Ehlers-Danlos syndrome remains undetected until the patient, usually in the pediatric age, shows extensive or severe mucocutaneous injuries after only minor traumas. | The reference suggests that minor physical trauma can cause severe injuries in patients with Ehlers-Danlos syndrome, which implies an exacerbation of symptoms; however, it does not directly address COL5A1-related cases specifically. |
| PMID:34740257 | PARTIAL | Haploinsufficiency of the Col5a1 gene encoding alpha(1) chain of type V collagen is the primary cause of classic Ehlers-Danlos syndrome. | While the article primarily discusses the genetic cause and molecular mechanisms, it indicates that the structural abnormalities in the extracellular matrix due to COL5A1 deficiency may contribute to symptom exacerbation following physical trauma. However, it does not directly state that physical trauma exacerbates symptoms. |
| PMID:36405827 | SUPPORT | Compromised brain tissues and cerebrovasculature could leave these patients vulnerable to mild traumatic brain injury (TBI), with increased severity and duration of post-concussive symptoms and delayed recovery. | The reference discusses increased vulnerability to traumatic brain injury and severe post-concussive symptoms in presumed Ehlers-Danlos syndrome patients, supporting the notion that physical trauma exacerbates symptoms. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:22616833 | SUPPORT | The topics addressed in this issue are Ehlers-Danlos syndrome and associated chronic pain; the information is meant to help readers understand the mechanisms for pain in this connective tissue disorder as well as general treatment principles for chronic pain management. | The reference discusses chronic pain management in the context of Ehlers-Danlos syndrome, aligning with the statement about management of pain. |
| PMID:33741806 | SUPPORT | Evidence supporting physical therapy and occupational therapy is provided... Treatment should be individualized. | The reference discusses the role of physical therapy in the management of hypermobile Ehlers-Danlos syndromes (hEDS), which aligns with the statement about physical therapy to strengthen joints. |
| PMID:9042913 | NO_EVIDENCE | These findings confirm the causal role of collagen V in at least a subgroup of EDS I. | The reference focuses on the genetic aspect and causal mutations in COL5A1 related to Ehlers-Danlos syndrome but does not delve into treatments. |
| PMID:35162892 | NO_EVIDENCE | Treatment is currently symptomatic and focuses on increasing the quality of life of these patients, as there is no curative treatment. | The reference mentions symptomatic treatment but does not provide specific details on pain management, physical therapy, or prevention of complications for COL5A1-related Ehlers-Danlos syndrome. |
| PMID:32941194 | NO_EVIDENCE | Although medical interventions to help halt the disease progression remain limited, improved awareness of vEDS by patients and practitioners have resulted in increased average life expectancy. | The reference discusses limited medical interventions and management of vascular Ehlers-Danlos syndrome (vEDS), which is different from COL5A1-related EDS. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:8274350 | PARTIAL | Manifestations are highly variable, and include numerous skin abnormalities. Nurses play an important role in helping patients and their families live with this unusual disorder. | The reference mentions skin abnormalities but does not provide explicit details on treatments related to wound care or scar management. |
| PMID:2728341 | PARTIAL | Although delayed wound healing has been reported to be a complication of Ehlers-Danlos syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with Ehlers-Danlos syndrome appears to be similar to nonaffected animals. | This reference discusses wound healing in animal models of EDS but indicates that delayed healing, a common complication in human EDS patients, was not observed in the studied animals. |
| PMID:28387435 | SUPPORT | Classic Ehlers-Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. | This reference identifies poor wound healing as a complication associated with classic EDS due to COL5A1 mutations, which supports the need for careful attention to wound healing and scar management. |
| PMID:37594181 | SUPPORT | The classic tragic facial expression was observed as well as chronic pruritus and mild hyperesthesia. Histology showed sparse, disorganized collagen and an increase in cutaneous mast cells. Electron microscopy identified ultrastructural defects commonly seen in collagen type V alpha 1 chain (COL5A1) variants including flower-like collagen fibrils in cross-section. | This detailed observation of classic EDS symptoms and associated collagen abnormalities highlights the importance of wound and scar care in patients. |
| PMID:26005130 | SUPPORT | Non-operative treatment is preferable, but for carefully selected patients, specific joint stabilization and nerve decompression procedures can provide symptomatic relief when conservative measures fail. | This reference emphasizes the preference for non-operative treatments for EDS, implying a role for conservative measures such as wound care and scar management without extensive surgical intervention. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:21193204 | SUPPORT | Echocardiography may still be warranted as part of cardiovascular assessment, but decreased frequency of screening is recommended especially in symptom-free adults. | This reference supports cardiovascular monitoring in Ehlers-Danlos Syndrome, particularly for mitral valve prolapse and aortic dilation. |
| PMID:15607555 | SUPPORT | This proposal is specifically concerned with Ehlers-Danlos syndrome classic type (formerly Types I-III), which is characterized by [...] cardiac mitral valve prolapse. | This reference supports the need for evaluation in Ehlers-Danlos Syndrome for cardiovascular complications like mitral valve prolapse. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:26376608 | SUPPORT | CONCLUSIONS & INFERENCES: EDS HM and other subtypes should be considered in patients with chronic functional GI symptoms and abdominal vascular lesions. | This study highlights the prevalence of gastrointestinal manifestations in patients with various subtypes of EDS, indicating that GI management, including treatment of conditions like gastroesophageal reflux, is indeed a necessary part of the overall treatment plan. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:17067502 | PARTIAL | Preparticipation cardiothoracic and orthopedic screening is highly recommended for athletes with EDS, and appropriate cardiovascular, orthopedic, gastrointestinal, neurologic, and dermatologic management can often allow patients with EDS to remain active. | The literature emphasizes careful screening and multidisciplinary management for athletes with EDS, which implicitly supports the avoidance of high-impact activities to prevent injuries but does not explicitly mention the use of protective gear or contact sports. |
| PMID:32899328 | PARTIAL | The major clinical manifestations of EDS include joint hypermobility, skin hyperextensibility, and generalized connective tissue fragility. These findings allow healthcare providers to know more about this disease in order to support and give advice to patients about the changes they will have to make. | The study highlights the importance of providing advice to patients about lifestyle changes due to EDS but does not specifically mention avoiding high-impact activities or using protective gear. |