The spectrum of gastrointestinal functional bowel disorders in joint hypermobility syndrome and in an academic referral center.

Joint hypermobility syndrome (JHS) is a non-inflammatory hereditary disorder of connective tissue with varied clinical presentations, including frequent joint dislocations, hyperextensible skin, easy bruising, and abnormal paper-thin scar formation. Many of these patients have unexplained gastrointestinal (GI) symptoms. Our aim was to evaluate the prevalence of JHS in a tertiary gastroenterology motility clinic and the spectrum of functional bowel disorders in JHS patients. In this retrospective case series, we screened the medical records of 277 patients seen over 4 years at an academic GI Motility Center. The patients who met the criteria for JHS by Beighton hypermobility score were evaluated for the presence of functional GI disorders by Rome IV criteria. They also underwent gastric emptying study and glucose breath testing for small intestinal bacterial overgrowth. The prevalence of JHS in the study population was 9.7%. The mean age was 27 years, and 92.5% were female. The symptoms experienced by these patients include nausea/vomiting (89%), abdominal pain (70%), constipation (48%), and bloating (18.5%). The disorders associated with JHS include gastroparesis (52%), irritable bowel syndrome (55.5%), and gastroesophageal reflux disease (30%). Also, 10 patients (37%) were diagnosed with postural hypotension tachycardia syndrome secondary to autonomic dysfunction. Approximately 10% of patients with suspected functional bowel disorders have hypermobility syndrome. Hence, it is crucial to familiarize gastrointestinal practitioners with the criteria utilized to diagnose JHS and the methods to identify physical examination findings related to this condition.

An Absent Lingual Frenulum in a Non-syndromic Premature Infant.

The lingual frenulum (LF) is a fold of tissue that connects the tongue to the oral cavity's floor. Abnormal frenula are associated with speech alterations. The absence of the LF is associated with Ehler's Danlos syndrome (EDS). In this case report, we present a premature infant incidentally found to have an absent lingual frenulum, with recurrent desaturations during feeding. The desaturations were believed to be due to the absent lingual frenulum, but they resolved after one month without treatment and were then attributed to apnea of prematurity. Whole exome sequence showed no genetic disorders. The infant is now doing well with no interventions. An absent lingual frenulum warrants molecular genetic testing for EDS. However, it does not warrant any treatment; special considerations are only required during intubation.

Uncovering Ankylosing Spondylitis from a Diagnosis of Parsonage-Turner Syndrome: A Case Report of Bilateral Shoulder Pain and Weakness.

Introduction: Parsonage-Turner syndrome is a rare condition that is often misdiagnosed by physicians due to the overlapping symptoms with other conditions such as rotator cuff injury and cervical radiculopathy. The etiology of the Parsonage-Turner syndrome is unknown, but has been associated with an immune-mediated response to rheumatic disease, infection, surgery, and immunizations. Case Presentation: A 18-year-old female former tennis player with a history of complex regional pain syndrome (CRPS), Ehler-Danlos syndrome (EDS), and two prior right shoulder surgeries presented to the orthopaedic clinic with bilateral shoulder pain. After a third surgery on the right shoulder, the patient later developed constant burning and sharp pain around the right shoulder that radiated toward the chest. She also experienced numbness, tingling, and weakness in the right shoulder along with pain and weakness in the left shoulder. The patient was tender over the right musculocutaneous nerve and both shoulders were inflamed on ultrasound. Electromyography (EMG) and nerve conduction studies were performed, which were consistent with a bilateral subacute on chronic brachial plexopathy, suggestive of Parsonage-Turner syndrome. Rheumatology was consulted due to an extensive family history of autoimmune diseases, leading to an additional diagnosis of ankylosing spondylitis. The patient's bilateral shoulder pain slowly improved over the following year with physical therapy and prolotherapy treatments. Conclusion: The case described, herein, represents a unique patient who presents with the rare conditions of ankylosing spondylitis, CRPS, EDS, and Parsonage-Turner syndrome. EMG was critical to differentiate Parsonage-Turner syndrome from the overlapping CRPS symptoms and without this, the diagnosis of ankylosing spondylitis may have been delayed. It is imperative physicians take a thorough history, include uncommon or rare conditions as a potential diagnosis, and undergo thorough testing while evaluating a patient to avoid unnecessary treatment therapies and patient dissatisfaction.

Obstructive sleep apnea in a case of ehlers-danlos syndrome.

Ehlers-Danlos Syndrome (EDS) is a group of rare connective tissue disorders characterized by genetic defects in collagen and connective tissue synthesis and structure, with manifestations ranging from asymptomatic or mild skin and joint hyperlaxity to severe physical disability. Mild asymptomatic forms of Ehlers-Danlos syndrome seems to be under diagnosed and may have severe systemic complications mainly cardio vascular. Cartilaginous defects in the head and neck region increase the risk of Sleep-Disordered Breathing (SDB) especially Obstructive Sleep Apnea (OSA). It is well admitted now that OSA has many, frequently cardiovascular, adverse effects which are added to the risk of Ehlers-Danlos Syndrome's itself cardiovascular complications. We report a case of EDS diagnosed since childhood with a long history of fatigue, daytime somnolence, snoring and unrefreshing sleep. Although the diagnosis of sleep apnea was suspected because of worsening of his symptoms ten years prior to his referral to our sleep laboratory, he was never investigated for Sleep-disordered breathing and was lost to follow up. This case report relays what is stated in the literature regarding the association of SDB, mainly OSA, with EDS and its toll on the health of such individuals.

Novel regulatory roles of small leucine-rich proteoglycans in remodeling of the uterine cervix in pregnancy.

The cervix undergoes rapid and dramatic shifts in collagen and elastic fiber structure to achieve its disparate physiological roles of competence during pregnancy and compliance during birth. An understanding of the structure-function relationships of collagen and elastic fibers to maintain extracellular matrix (ECM) homeostasis requires an understanding of the mechanisms executed by non-structural ECM molecules. Small-leucine rich proteoglycans (SLRPs) play key functions in biology by affecting collagen fibrillogenesis and regulating enzyme and growth factor bioactivities. In the current study, we evaluated collagen and elastic fiber structure-function relationships in mouse cervices using mice with genetic ablation of decorin and/or biglycan genes as representative of Class I SLRPs, and lumican gene representative of Class II SLRP. We identified structural defects in collagen fibril and elastic fiber organization in nonpregnant mice lacking decorin, or biglycan or lumican with variable resolution of defects noted during pregnancy. The severity of collagen and elastic fiber defects was greater in nonpregnant mice lacking both decorin and biglycan and defects were maintained throughout pregnancy. Loss of biglycan alone reduced tissue extensibility in nonpregnant mice while loss of both decorin and biglycan manifested in decreased rupture stretch in late pregnancy. Collagen cross-link density was similar in the Class I SLRP null mice as compared to wild-type nonpregnant and pregnant controls. A broader range in collagen fibril diameter along with an increase in mean fibril spacing was observed in the mutant mice compared to wild-type controls. Collectively, these findings uncover functional redundancy and hierarchical roles of Class I and Class II SLRPs as key regulators of cervical ECM remodeling in pregnancy. These results expand our understating of the critical role SLRPs play to maintain ECM homeostasis in the cervix.

Rare neurological manifestations in a Saudi Arabian patient with Ehlers-Danlos syndrome and a novel homozygous variant in the TNXB gene.

We report a 38-year-old Saudi male with Ehlers-Danlos Syndrome (EDS). The patient presented with rare and unusual neurological manifestations, including but not limited to ophthalmoplegia and myopathic pattern on his electromyography. In addition to hand weakness, there was skin hyperextensibility, joint hyperflexibility, and frontal baldness. Next-generation sequencing was performed on target exon sequences, using whole exome sequencing and Burrows-Wheeler Aligner for alignment/base calling. Genome Analysis Toolkit and reference genome Homo sapiens (UCSC hg19) were used for sequence processing and analysis. Variant classification was done according to standard international recommendations. A novel homozygous variant, NM_019105.6: c.8488C>T p.(Gln2830*), was detected in the TNXB gene. This variant is not reported in the literature nor dbSNP or gnomAD databases. Additionally, this variant is predicted to create a premature stop codon and produce a truncated protein or nonsense-mediated mRNA decay. Hence, it is classified as a likely pathogenic variant. The same point variant was found in a heterozygous state in the patient's father and sister. Both presented with milder symptoms associated with Ehlers-Danlos syndromes and heritable connective tissue disorders. Therefore, the patient was diagnosed as a tenascin-X (TNX) deficient type of EDS known as classical-like Ehlers-Danlos syndrome. TNX deficient patients may present with clinical and electrophysiological manifestations that are unusual in EDS like frontal baldness, ophthalmoplegia, and myotonia, which mimic myotonic dystrophy type I. Clinicians should be aware of the potential overlap of symptoms among these two diseases to ensure correct diagnosis is made.

Evaluation of Temporomandibular Disorders and Comorbidities in Patients with Ehler--Danlos: Clinical and Digital Findings.

OBJECTIVE: The objective of this study is to recognize representative cranio-cervico-mandibular features of patients with Ehler-Danlos syndrome and associated temporomandibular disorders (TMDs), to assess a targeted and integrated treatment plan. MATERIALS AND METHODS: After a diagnosis of disease, 38 individiuals with Ehler-Danlos syndrome and temporomandibular symptomatology referred were evaluated. Gnathological evaluation, according to the Diagnostic Criteria for TMDs, and radiographic imaging was performed. In addition, digital evaluation of occlusal and muscular balance, using surface electromyography of jaw muscles, was conducted. Statistical software for data analysis - STATA (StataCorp, College station, Texas, USA) - was used. RESULTS: Most common temporomandibular dysfunctions were arthralgia, myalgia, disc displacement with reduction and subluxation. Headache and neck pain were the most frequent comorbidities. Somatization, depression, anxiety, and obsessive-compulsive behavior were the most recurrent psychological disorders. Electromyographic analysis showed out of normal range data. CONCLUSION: Early diagnosis and interception are requested to avoid injuries and repeated traumatism. Multidisciplinary treatments are available to approach all the aspects of the syndrome.

Brugada Syndrome in a Patient with Vascular Ehlers-Danlos Syndrome: Sudden Death Risk Amplified.

The vast majority of sudden cardiac arrests occur in patients with structural heart disease and in approximately 10% of the cases, it can occur in those with structurally normal hearts. Brugada syndrome is an autosomal dominant sodium channelopathy that has been implicated in sudden deaths. Given their low prevalence, our knowledge about Brugada syndrome is still evolving. Apart from schizophrenia, there have been no reports of associated medical conditions. We recently encountered a patient with vascular Ehlers-Danlos syndrome who was also found to have Brugada syndrome. Both these conditions share some common clinical presentations including a propensity for sudden death.

Congenital keratoglobus with multiple cardiac anomalies: a case presentation and literature review.

Keratoglobus is a rare condition of bilateral corneal ectasia, which results in high myopia, irregular astigmatism, scarring, and rarely spontaneous globe rupture. Globoid protrusion of a clear, diffusely thin cornea is the pathology. The congenital form has been associated with blue sclera in which there is a systemic connective tissue disorder with abnormal collagen synthesis like Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta. Some concomitant abnormalities reported with kertoglobus include joint hypermobility, dental and skeletal abnormalities, osteal fragility, and deafness. Acquired forms have been reported to be associated with vernal keratoconjunctivitis and thyroid ophthalmopathy. We report the case of a 16-year-old boy with keratoglobus who presented with a history of photophobia and a low vision in both eyes since birth. He has been followed up by our pediatric cardiology department due to multiple cardiac anomalies. He had hypermobility of large joints, easy bruising, thin and hyperextensible skin with visible veins, which were also described in his elder brother. We aimed to discuss the etiology and the association of keratoglobus with some systemic abnormalities caused by collogen tissue disturbance, and make a brief review about the recent literature concerning the management of keratoglobus patients.

Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome.

Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure.

Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure.

Niccolo Paganini: aspectos médicos de su vida y obra / Niccolo Paganini: medical aspects of his Ufe and work

Niccolo Paganini is the most virtuos violinist of the history of music. He even received the nick name of "the violinist of the evil" for his outstanding skills on stage performance. It has been suggested that he had syphilis and tuberculosis, the commonest diseases of that time, but this hypothesis remains speculative. There are suggestions that he was the victim of iatrogenic mercurial poisoning. Furthermore, his body build suggests the presence of Ehlers-Danlos syndrome which could give him special anatomical conditions allowing him to achieve an amazing level of vírtuousness in his art. We herein review the medical aspects ofthis brilliant musician's life.