Victor Almon McKusick (VAM) is widely recognized as the father of the field of medical genetics. He established one of the first medical genetics clinics in the United States at Johns Hopkins in 1957 ...and developed a robust training program with the tripartite mission of education, research, and clinical care. Thousands of clinicians and scientists were educated over the years through the Short Course in Medical and Molecular Genetics, which VAM founded with Dr. Thomas Roderick in 1960. His Online Mendelian Inheritance in Man (OMIM), a catalog of human genes and genetic disorders, serves as the authoritative reference for geneticists around the globe. Throughout his career he was an advocate for mapping the human genome. He collaborated with Dr. Frank Ruddle in founding the International Human Gene Mapping Workshops in the early 70's and was an avid proponent of the Human Genome Project. He was the founding President of the Human Genome Organization and a founding editor of the journal Genomics. His prodigious contributions to the field of medical genetics were recognized by multiple honors, culminating with the Japan Prize in 2008.
Respiratory manifestations in the Ehlers–Danlos syndromes Bascom, Rebecca; Dhingra, Radha; Francomano, Clair A.
American journal of medical genetics. Part C, Seminars in medical genetics,
December 2021, 2021-12-00, 20211201, Letnik:
187, Številka:
4
Journal Article
Persons with the Ehlers–Danlos syndromes (EDS) report a wide range of respiratory symptoms, most commonly shortness of breath, exercise limitation, and cough. Also reported are noisy breathing ...attributed to asthma, difficulty with deep inhalation, and inspiratory thoracic pain. The literature consists of case reports and small cross‐sectional and cohort studies. One case–control study estimated twofold to threefold greater respiratory disease burden among persons with EDS as compared to controls. The differential diagnosis for symptoms is broad. Structural alterations include pectus deformities, scoliosis, recurrent rib subluxations, and tracheobronchomalacia, associated with varying degrees of physiologic impairment. Those with vascular EDS have an increased risk of pneumothorax, intrapulmonary bleeding, cysts, and nonmalignant fibrous nodules. Functional aerodigestive manifestations such as inducible laryngeal obstruction may be misdiagnosed as asthma, with gastro‐esophageal dysmotility and reflux as common contributing factors. Inflammatory manifestations include costochondritis, bronchiectasis, and localized respiratory allergic and nonallergic mast cell activation. Cranio‐cervical instability can dysregulate respiratory control pathways. There is a need for careful phenotyping using standardized clinical tools and patient‐reported outcomes and continuing collaboration with aerodigestive specialists including otolaryngologists and gastroenterologists. Also needed is further evaluation of respiratory symptoms in persons with hypermobility spectrum disorders. Personalized monitoring strategies are invaluable for interpretation and long‐term management of respiratory symptoms.
Despite well-established clinical associations between Hypermobile Ehlers-Danlos syndrome (hEDS) and postural orthostatic tachycardia syndrome (POTS), the precise prevalence is unknown. We therefore ...evaluated for hEDS in 91 POTS participants using the 2017 hEDS diagnostic checklist, which has three major criteria: 1) generalized joint hypermobility (Beighton score), 2) systemic features, family history, and 3) absence of exclusion criteria. Overall, 28 out of 91 POTS participants (31%) met clinical criteria for hEDS. An additional 24% of participants had generalized joint hypermobility without meeting hEDS criteria. Identifying the prevalence of hEDS in POTS is important for understanding possible mechanisms connecting these two syndromes.
Ehlers–Danlos syndrome, classical type Bowen, Jessica M.; Sobey, Glenda J.; Burrows, Nigel P. ...
American journal of medical genetics. Part C, Seminars in medical genetics,
March 2017, Letnik:
175, Številka:
1
Journal Article
AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP ...is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1−/− mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC p.Asn490_Met495delins(40) and c.1743C>A p.Cys581∗) in the first individual, a homozygous variant (c.1320_1326del p.Arg440Serfs∗3) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype.
Pain management in the Ehlers–Danlos syndromes Chopra, Pradeep; Tinkle, Brad; Hamonet, Claude ...
American journal of medical genetics. Part C, Seminars in medical genetics,
March 2017, Letnik:
175, Številka:
1
Journal Article
To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue ...disorders in those with orthostatic intolerance in the context of both clinical care and research.
We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance.
We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life.
There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings.
Objective
Joint hypermobility in Ehlers‐Danlos Syndromes (EDS) predisposes persons with EDS to frequent subluxations and dislocations, chronic arthralgia, and soft‐tissue rheumatism. Epidemiologic ...trends of rheumatologic conditions among persons with EDS are lacking. Prescription claims databases can reflect underlying disease burdens by using medication claims as disease proxies. We examined the prevalence of prescription claims for commonly prescribed immunomodulator and antiinflammatory (IMD) drugs among persons with EDS compared with their matched control person, and hypothesized peripubertal increases among female persons with EDS.
Methods
We compared the percentages of IMD drug prescription claims among 3,484 persons with EDS (ages 5–62 years) against their age‐, sex‐, state of residence‐, and earliest claim date–matched control persons using 10 years (2005–2014) of private prescription claims data and a minimum 2‐year enrollment inclusion criterion.
Results
Our cohort comprised 70% adults and 74% female persons. At least 1 IMD medication was prescribed to 65.4% of persons with EDS compared with 47.4% of control persons. We observed 1.3 to 4.2 times higher odds (P < 0.0001) for 5 out of 6 IMD drug classes among persons with EDS compared with matched control persons, except for biologic agents (conditional odds ratio 1.3, 95% confidence interval 0.8–2.0). Peripubertal increases were observed for nonsteroidal antiinflammatory drugs, oral, and injectable steroids.
Conclusions
To our knowledge, our study is the first to examine the full range of IMD drug prescription claim trends among persons with EDS. We believe our research findings can have notable diagnostic and management implications for EDS patients who present with multiple comorbidities and generally require a more granular assessment of their medical conditions.
PDF
