OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with Ehlers-Danlos syndrome, spondylodysplastic type 2 (EDSSPD2). METHODS: A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in July 2024 for "delayed motor development for 1 and a half year" was selected as the study subject. Clinical data of the child was collected, including medical history, family history, and results of auxiliary examinations. Peripheral venous blood samples were collected from the child and his two brothers and both parents. Genomic DNA was extracted from the child and his family members and subjected to whole-exome sequencing (WES) and copy number variation (CNV) analysis. Sanger sequencing was used to verify the parental origin of the candidate variants. Multiple protein function prediction software tools, including SIFT, PolyPhen-2, and REVEL, were used to assess the impact of candidate variants on the protein function. Based on protein database information from UniProt, a two dimensional structural schematic of the target protein was generated. The pathogenicity of the variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on the B3GALT6 gene variants leading to EDSSPD2 was retrieved from CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases. The procedures followed in this study were reviewed and approved by the Medical Ethics Committee of Affiliated Hospital of Guangdong Medical University (Ethics No.：PJ2021-097). RESULTS: The proband was a 2-year-old male with an onset in infancy. The main clinical manifestations included loose skin, scoliosis and kyphosis, generalized hypermobility of joints, and motor developmental delay. WES has revealed two compound heterozygous variants of the B3GALT6 gene (NM_080605.4): c.766C>T (p.Arg256Trp) and c.962G>A (p.Cys321Tyr). Sanger sequencing verification showed that the c.766C>T and c.962G>A variants were respectively derived from his phenotypically normal father and mother. Bioinformatics analysis showed that for the c.766C>T (p.Arg256Trp) variant, the Arg256 site is located within the galactosyltransferase catalytic domain (GalT domain) of the β3GalT6 protein. According to the ACMG guidelines, the c.766C>T variant was classified as a likely pathogenic (PS3+PM2_supporting+PM3+PP3), and the c.962G>A was classified as a variant of unknown significance (PM2_Supporting+PM3+PP3). By following the pre-set literature retrieval strategy, a total of 12 articles related to B3GALT6 gene variants were identified (11 English and 1 Chinese), which involved a total of 71 patients. Among these, 4 reports (involving 20 patients) involved B3GALT6 gene variants leading to EDSSPD2. Among the 18 live-born EDSSPD2 patients (including the proband in this study), common clinical manifestations have included scoliosis (88.9%, 16/18), generalized hypotonia (83.3%, 15/18), and soft and lax skin (66.7%, 12/18). Some patients already showed skeletal abnormalities on prenatal ultrasound scan (22.2%, 4/18), while a few presented with cervical instability (16.7%, 3/18). One child had deceased at 18 months of age due to hypoxia caused by tracheomalacia and tracheal compression due to scoliosis. Among the 23 reported EDSSPD2 related B3GALT6 variant sites, missense variants were the most common (78.3%, 18/23), followed by nonsense variants (21.7%, 5/23). CONCLUSION Above finding has enriched the clinical and mutational spectra of EDSSPD2. Early genetic testing has important clinical value for the diagnosis, differential diagnosis, and genetic counseling of this disease.
Humans ; Male ; Ehlers-Danlos Syndrome/genetics* ; Pedigree ; N-Acetylgalactosaminyltransferases/genetics* ; Asian People/genetics* ; DNA Copy Number Variations ; Exome Sequencing ; Female ; Child ; Child, Preschool ; Phenotype ; Mutation ; China ; East Asian People ; Galactosyltransferases

Ehlers-Danlos syndrome (EDS) is an inherited disorder of collagen biosynthesis and structure, characterized by skin hyperextensibility, joint hypermobility, aberrant scars, and tissue friability. Besides the skin, skeleton (joint) and vessels, other organs such as the eyes and the intestine can be affected in this syndrome. Accordingly, interdisciplinary cooperation is necessary for a successful treatment. Three basic surgical problems are arising due to an EDS: decreased the strength of the tissue causes making the wound dehiscence, increased bleeding tendency due to the blood vessel fragility, and delayed wound healing period. Surgery patients with an EDS require an experienced surgeon in treating EDS patients; the treatment process requires careful tissue handling and a long postoperative care. A surgeon should also recognize whether the patient shows a resistance to local anesthetics and a high risk of hematoma formation. This report describes a patient with a wide open wound on the foot dorsum and delayed wound healing after the primary approximation of the wound margins.
Anesthetics, Local ; Blood Vessels ; Cicatrix ; Collagen ; Connective Tissue Diseases ; Ehlers-Danlos Syndrome ; Foot ; Hematoma ; Hemorrhage ; Humans ; Intestines ; Joint Instability ; Postoperative Care ; Skeleton ; Skin ; Wound Healing ; Wounds and Injuries

BACKGROUND: People with the Ehlers-Danlos Syndromes (EDS), a group of heritable disorders of connective tissue, often report experiencing dental procedure pain despite local anesthetic (LA) use. Clinicians have been uncertain how to interpret this apparent LA resistance, as comparison of EDS and non-EDS patient experience is limited to anecdotal evidence and small case series. The primary goal of this hypothesis-generating study was to investigate the recalled adequacy of pain prevention with LA administered during dental procedures in a large cohort of people with and without EDS. A secondary exploratory aim asked people with EDS to recall comparative LA experiences. METHODS: We administered an online survey through various social media platforms to people with EDS and their friends without EDS, asking about past dental procedures, LA exposures, and the adequacy of procedure pain prevention. Among EDS respondents who both received LA and recalled the specific LA used, we compared agent-specific pain prevention for lidocaine, procaine, bupivacaine, mepivacaine, and articaine. RESULTS: Among the 980 EDS respondents who had undergone a dental procedure LA, 88% (n = 860) recalled inadequate pain prevention. Among 249 non EDS respondents only 33% (n = 83) recalled inadequate pain prevention (P < 0.001 compared to EDS respondents). The agent with the highest EDS-respondent reported success rate was articaine (30%), followed by bupivacaine (25%), and mepivacaine (22%). CONCLUSIONS: EDS survey respondents reported nearly three times the rate of LA non-response compared to non-EDS respondents, suggesting that LAs were less effective in preventing their pain associated with routine office dental procedures.
Anesthesia, Local ; Anesthetics, Local ; Bupivacaine ; Carticaine ; Cohort Studies ; Connective Tissue ; Dental Care ; Ehlers-Danlos Syndrome ; Friends ; Humans ; Lidocaine ; Mepivacaine ; Procaine ; Social Media ; Surveys and Questionnaires

Ehlers-Danlos syndrome (EDS) VIII is an autosomal dominant inherited connective tissue disorder characterized by intractable periodontal inflammation, absence of gingiva, pretibial plaques, skin hyperextensibility, joint hypermobility, and tissue fragility with onset in the childhood or adolescence. In a recent report, heterozygous variants of the C1R or C1S related to the classical complement pathway were identified in families with history of EDS VIII. The current report describes a Korean 34-year-old female carrying a novel missense variant of C1R c.925T>G (p.Cys309Gly) and exhibiting early severe periodontitis, skin fragility, and joint hypermobility. The patient also had frontal, parietal, and temporal white matter brain lesions without definite vascular abnormalities on brain magnetic resonance imaging, which have not been surveyed meticulously in EDS VIII. Considering the genetic alteration of classic complement pathways in this condition, it is necessary to carefully observe multisystemic inflammation processes such as changes in brain white matter.
Adolescent ; Adult ; Brain ; Complement C1r ; Complement Pathway, Classical ; Complement System Proteins ; Connective Tissue ; Ehlers-Danlos Syndrome ; Female ; Gingiva ; Humans ; Inflammation ; Joint Instability ; Magnetic Resonance Imaging ; Periodontitis ; Rabeprazole ; Skin ; White Matter

Arterial tortuosity syndrome (ATS) is a very rare autosomal recessive connective tissue disease characterized by generalized elongation and tortuosity of the medium- to large-sized arteries, and other systemic connective tissue manifestations. To date, this disease entity has not been reported in Korea. We report a case of ATS diagnosed in a neonate who presented with severe elongation and tortuosity of the aorta and its major branches, as well as the intracranial arteries. Additionally, the patient presented with a tortuous dilatation of the inferior vena cava, an aneurysmal dilatation of the extra-hepatic bile ducts, and an inguinal and sliding hiatal hernia. The diagnosis was confirmed using DNA sequencing analysis, and the patient demonstrated a compound heterozygosity for two novel mutations (c.738delG [p.Gln247Serfs*33] and c.362T>C [p.Ile121Thr]) in exon 2 of the SLC2A10 gene. Genetic analysis also confirmed that both parents were heterozygous carriers of the responsible mutations. Owing to such clinical manifestations, ATS is often misdiagnosed as other connective tissue diseases including Loeys-Dietz syndrome, Marfan syndrome, and Ehlers-Danlos syndrome. In patients presenting with a high index of suspicion, thorough clinical evaluation and screening for ATS including computed tomography or magnetic resonance angiography and target gene analysis are necessary for early diagnosis and management.
Aneurysm ; Aorta ; Aortic Aneurysm ; Arteries ; Bile Ducts ; Connective Tissue ; Connective Tissue Diseases ; Diagnosis ; Dilatation ; Early Diagnosis ; Ehlers-Danlos Syndrome ; Exons ; Hernia, Hiatal ; Humans ; Infant, Newborn ; Joint Instability ; Korea ; Loeys-Dietz Syndrome ; Magnetic Resonance Angiography ; Marfan Syndrome ; Mass Screening ; Parents ; Sequence Analysis, DNA ; Vascular Malformations ; Vena Cava, Inferior

A 1-year-old Korean domestic short-haired cat presented with skin hyperextensibility and a severely macerated wound on the skin of the dorsal part of the neck. Diagnostic studies including histopathology and skin extensibility index revealed congenital cutaneous asthenia (Ehlers-Danlos syndrome). In this cat, the skin wounds and defects were successfully managed with standard wound management and cosmetic surgery. Although skin hyperextensibility is persistent, the cat has lived well without other complications to date. To the best of our knowledge, this is the first report of cutaneous asthenia in a cat in Korea.
Animals ; Asthenia* ; Cats* ; Ehlers-Danlos Syndrome ; Joint Instability ; Korea ; Neck ; Skin ; Surgery, Plastic ; Wounds and Injuries

Primary dissection of the renal artery is rare. Spontaneous renal artery dissection can be associated with diseases such as medial degeneration, neurofibromatosis, syphilitic arteritis, tuberculosis, polyarteritis nodosa, Marfan syndrome, fibromuscular dysplasia, or Ehlers-Danlos syndrome (EDS). Among these causes, EDS related renal artery dissection is very rare worldwide and has not been previously reported in Korea. EDS are a group of heritable connective tissue disorders characterized by fragility of the skin and hypermobility of the joints. We describe the case history of a young man who presented with left side flank pain, hypermobility of the hand joints and showed left renal artery dissection on computed tomography and angiography that turned out to be the first complication of vascular type EDS.
Angiography ; Arteritis ; Connective Tissue ; Ehlers-Danlos Syndrome* ; Fibromuscular Dysplasia ; Flank Pain ; Hand Joints ; Joints ; Korea ; Marfan Syndrome ; Neurofibromatoses ; Polyarteritis Nodosa ; Renal Artery* ; Skin ; Tuberculosis

Ehlers-Danlos syndrome type IV (EDS IV) is a hereditary disorder of the connective tissue, characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations of the gene for type III procollagen (COL3A1), resulting in insufficient collagen production or a defect in the structure of collagen. EDS IV can have fatal complications such as the rupture of great vessels or organs, which can cause hemorrhaging and sudden unexpected death. Here, we report a case of a 43-year-old female who collapsed after a struggle with a neighbor. In this patient, the bifurcation of the bilateral common iliac artery ruptured, with no evidence of trauma, inflammation, or atherosclerosis. Genetic analysis of COL3A1 showed the presence of a c.2771G>A (p.Gly924Arg) mutation, which may be associated with EDS IV. The forensic pathologist should consider the possibility that the spontaneous visceral or arterial rupture was caused by EDS IV. Genetic analysis is not currently a routine procedure during autopsy. However, in this case, we suggest that the patient possibly had an underlying EDS IV condition, and we recommended family members of the deceased to seek genetic analysis and counseling.
Adult ; Aortic Rupture* ; Arteries ; Atherosclerosis ; Autopsy ; Collagen ; Collagen Type III ; Connective Tissue ; Counseling ; Ehlers-Danlos Syndrome* ; Female ; Humans ; Iliac Artery ; Inflammation ; Rupture ; Rupture, Spontaneous ; Skin ; Uterus ; Veins

Ehlers-Danlos syndrome is an autosomal dominant hereditary disorder of connective tissue, while familial gigantiform cementoma is a condition that usually manifests as multiple radiopaque cementum-like masses throughout the jaws. This case report discusses the oral management and prosthetic rehabilitation of two patients presenting familial gigantiform cementoma with Ehlers-Danlos Syndrome.
Cementoma* ; Connective Tissue ; Ehlers-Danlos Syndrome ; Humans ; Jaw ; Rehabilitation

Ehlers-Danlos syndrome is an autosomal dominant hereditary disorder of connective tissue, while familial gigantiform cementoma is a condition that usually manifests as multiple radiopaque cementum-like masses throughout the jaws. This case report discusses the oral management and prosthetic rehabilitation of two patients presenting familial gigantiform cementoma with Ehlers-Danlos Syndrome.
Cementoma* ; Connective Tissue ; Ehlers-Danlos Syndrome ; Humans ; Jaw ; Rehabilitation