Presentation
A 37-year-old woman with LDS presented with numerous facial milia. She reported that the milia had been present since early childhood. Inspection of her skin revealed numerous striae. [jamanetwork.com]
We have given presentations at Grand Rounds in various hospitals. We have created a medical presentation and the “Head-to-Toe” checklist that we have presented to over 1300 medical professionals from around the world. [loeysdietzcanada.org]
Case presentation We report two cases of Loeys-Dietz syndrome precociously diagnosed. [ijponline.biomedcentral.com]
TAAs were present in 67% of the cases (4/6), and in Leutermann et al. aneurysms were present in two of the family members [ 18 ],[ 19 ]. [bmcmedgenet.biomedcentral.com]
[…] outcome, describe the presenting signs and symptoms, and discuss the clinical management. [tp.amegroups.com]
Entire Body System
- Arachnodactyly
Other skeletal findings included scoliosis, arachnodactyly, camptodactyly, and joint laxity ( Figure 5 ). [jamanetwork.com]
[…] aneurysm common iliac aneurysm splenic artery aneurysm intracranial aneurysm arterial tortuosity associated congenital cardiac abnormalities: patent ductus arteriosus atrial septal defects mitral valve prolapse left ventricular hypertrophy Musculoskeletal arachnodactyly [radiopaedia.org]
[…] root aneurysm (98%), arterial tortuosity (84%), other aneurysms (52%), hypertelorism (90%), cleft palate or abnormal uvula (90%), other craniofacial features including craniosynostosis (48%) and blue sclerae (40%), and skeletal abnormalities including arachnodactyly [ncbi.nlm.nih.gov]
“Skeletal” includes any bone or joints alterations (including arachnodactyly) apart from spine involvement, which is reported as “spine”. [ijponline.biomedcentral.com]
Features shared with MFS and LDS include aortic aneurysm, mainly in thoracic tract, pectus deformity, arachnodactyly, scoliosis, joint hypermobility, and striae distensae in young age. [bmcmedgenet.biomedcentral.com]
- Pain
Signs and symptoms of acute aortic dissection may include: Sudden onset, severe or sharp chest, back, neck/head, or abdominal pain Pain described as “ripping” or “tearing” Pain radiating (traveling) from the chest to the back, head and neck, abdomen, [gentacalliance.org]
Stomach and intestines can bleed or become inflamed, causing chronic problems such as abdominal pain, diarrhea, or problems absorbing nutrients. Learn more by calling us or visiting the Loeys-Dietz Syndrome Foundation > [stanfordchildrens.org]
[…] osteoporosis) that can make the bones more likely to break) Other Allergies to food and elements in the environment Stomach and intestine problems, such as difficulty absorbing food and chronic (comes and goes but never really goes away) diarrhea, abdominal pain [marfan.org]
Articular pain associated with joint hypermobility was not reported in literature so far in patients with LDS4, whereas both our patients referred chronic generalized articular pain. [bmcmedgenet.biomedcentral.com]
- Atrial Septal Defect
septal defects mitral valve prolapse left ventricular hypertrophy Musculoskeletal arachnodactyly camptodactyly pectus carinatum scoliosis talipes equinovarus joint laxity dolichostenomelia (unusually long limbs) cervical spine instability Other developmental [radiopaedia.org]
It can also cause arterial tortuosity, a twisting and lengthening of arteries, and heart defects noticed at birth, including bicuspid aortic valve, atrial septal defect, and patent ductus arteriosus. [stanfordchildrens.org]
Other features of Loeys-Dietz syndrome include: Cardiovascular Arteries that twist and wind (arterial tortuosity) Heart defects at birth (atrial septal defect, patent ductus arteriosis, bicuspid aortic valve) Eyes, Head and Neck Widely-spaced eyes (hypertelorism [marfan.org]
As for the cardiac involvement, patent ductus arteriosus (PDA), atrial septal defects, mitral valve prolapse, and bicuspid aortic valve are also relatively common finding. [ijponline.biomedcentral.com]
- Asymptomatic
Asymptomatic carotid artery stenosis screening in patients with lower extremity atherosclerosis: a prospective study. Ann Vasc Surg. 1997 Jul. 11(4):374-7. [Medline]. Delgado AL, Jahromi B, Muller N, Farhat H, Salame J, Zauner A. [medscape.com]
- Severe Pain
Surgical intervention with platypodia is also not indicated, except in cases of severe pain that limits walking [1]. Pathology of the cervical spine is a characteristic sign of types 1 and 2 Loeys–Dietz syndrome and occurs in 51% of cases [3, 31]. [journals.eco-vector.com]
Gastrointestinal
- Abdominal Pain
Stomach and intestines can bleed or become inflamed, causing chronic problems such as abdominal pain, diarrhea, or problems absorbing nutrients. Learn more by calling us or visiting the Loeys-Dietz Syndrome Foundation > [stanfordchildrens.org]
pain, and/or gastrointestinal bleeding and inflammation Rupture of the spleen or bowel Rupture of the uterus during pregnancy When a person has these particular features, it is important to be evaluated for Loeys-Dietz syndrome. [marfan.org]
Signs and symptoms of acute aortic dissection may include: Sudden onset, severe or sharp chest, back, neck/head, or abdominal pain Pain described as “ripping” or “tearing” Pain radiating (traveling) from the chest to the back, head and neck, abdomen, [gentacalliance.org]
Cardiovascular
- Vascular Disease
Keywords: TGFβ, Loeys-Dietz syndrome, vascular diseases, transforming, multipotential secreting, cytokines, aggressive arteriopathy, Elastin disarray, antagonism of TGFβ, pathologic hallmark [eurekaselect.com]
Animal research has led to the suggestion that TGFβ antagonists such as the angiotensin II type 1 receptor antagonist, losartan, might be beneficial in these syndromes and even in diabetic vascular disease. [ncbi.nlm.nih.gov]
It is imperative to diagnose LDS correctly because it is associated with very aggressive vascular disease. 8 Also, because LDS may be confused with other familial aneurysm syndromes, including Marfan syndrome, vascular Ehlers-Danlos syndrome, and Shprintzen-Goldberg [jamanetwork.com]
Before the aneurysmal disease associated with LDS is considered, the definitions pertaining to the degrees of vascular dilatation should be reviewed. [pubs.rsna.org]
- Hypertension
Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002 Mar 23. 359(9311):995-1003. [Medline]. [medscape.com]
Some authors report that left ventricular hypertrophy in patients with this syndrome is usually mild or moderate and occurs in the absence of aortic stenosis or arterial hypertension [21, 24]. [journals.eco-vector.com]
Eyes
- Blue Sclera
Disease spectrum and associated features include: Craniofacial hypertelorism cleft palate bifid uvula craniosynostosis malar hypoplasia blue sclerae Chiari I malformation hydrocephalus Cardiovascular aortic dissection aortic dilatation non-aortic aneurysms [radiopaedia.org]
sclerae (40%), and skeletal abnormalities including arachnodactyly (70%), pectus deformity (68%) and joint laxity (68%). [ncbi.nlm.nih.gov]
Sclera Blue sclerae have been linked to LDS.2,3,6,9,33 In total, blue sclerae were documented in five out of 275 patients with LDS. [emjreviews.com]
Blue sclera is noted in patients with Loeys–Dietz syndrome and is usually not registered in patients with Marfan syndrome [3]. [journals.eco-vector.com]
sclerae, a blue tinge to the whites of the eyes micrognathia, a small chin retrognathia, receding chin Skeletal system symptoms long fingers and toes contractures of the fingers clubfoot scoliosis, curvature of the spine cervical-spine instability joint [healthline.com]
Musculoskeletal
- Joint Dislocation
She had experienced numerous joint dislocations. She also had been diagnosed as having Marfan syndrome until evaluation in our institution identified a TGFBR2 mutation (p.Arg537Cys). [jamanetwork.com]
Doctors worry about: Increased heart rate and blood pressure can put added stress on the aorta Stress on the bones and joints can lead to added pain and joint dislocations Bruising and internal bleeding due to certain medications (such as blood thinners [gentacalliance.org]
dislocations, forearm bone dislocations, and joint extensor contractures), and skull. [journals.eco-vector.com]
Face, Head & Neck
- Hypertelorism
This is interesting because hypertelorism is considered to be a common clinical finding associated with LDS. [emjreviews.com]
The classical triad of Loeys-Dietz syndrome is described as 1 : arterial tortuosity and aneurysms hypertelorism bifid uvula or cleft palate Loeys-Dietz syndrome is rare, with prevalence estimated at less than one per 100,000. [radiopaedia.org]
Other facial features included hypertelorism and retrognathia. The oral cavity was notable for a high-arched palate and a broad uvula. [jamanetwork.com]
It is characterised by aortic and peripheral aneurysms and arterial tortuosity, bifid uvula and/or cleft palate, and hypertelorism, and is caused by mutations in the genes for the transforming growth factor β receptors 1 or 2 ( TGFBR1 at chromosome 9q33 [ncbi.nlm.nih.gov]
The extreme of clinical severity is represented by the Loeys-Dietz syndrome (LDS), an autosomal dominant disorder characterized by hypertelorism, bifid uvula, and/or cleft palate, and aggressive arteriopathy causing arterial tortuosity as well as life-threatening [eurekaselect.com]
Workup
Thus, it will be some time before they are used for routine clinical assessment of the vascular system in general and the workup of patients with LDS. Conclusion LDS is a recently described inherited vasculopathic syndrome. [pubs.rsna.org]
Treatment
Studies are ongoing to determine whether drug treatment of the Loeys-Dietz syndrome also may be of value. [medicinenet.com]
Management and Treatment How is Loeys-Dietz syndrome treated? Loeys-Dietz treatments are unique to each individual. Your care depends on the associated problems and symptoms. [my.clevelandclinic.org]
It’s important to meet with a doctor who is familiar with the disorder in order to determine a treatment plan. There’s no cure for the disorder, so treatment is aimed at preventing and treating symptoms. [healthline.com]
Is aortic root replacement surgery a necessary treatment? The goal of aortic root replacement surgery is to replace weak tissue before a tear occurs. [hopkinsmedicine.org]
We present our experience with the treatment and follow-up of pediatric patients with a diagnosis of MS or LDS. [revespcardiol.org]
Prognosis
Current surgical experience with LDS is excellent, offering a good long-term prognosis with timely identification of the disease. [insights.ovid.com]
In contrast to Loeys-Dietz syndrome, in other inherited syndromes associated with aortic aneurysms, surgery carries a poorer prognosis, and the aneurysms can be managed with medications for a longer period of time before surgery becomes necessary. [medicinenet.com]
Early prophylactic surgery is crucial to avoid catastrophic aortic complications and achieve a good long-term prognosis (2). [tp.amegroups.com]
Outlook / Prognosis What is the outlook for people with Loeys-Dietz syndrome? Loeys-Dietz syndrome is still a relatively new disease. Experts are still learning how it affects the quality of life and life expectancy. [my.clevelandclinic.org]
Also, the prognosis for people with LDS has improved over the years because of better recognition and preventative aortic surgery for enlargement of the aorta and branches. [gentacalliance.org]
Epidemiology
Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003 Jan. 2(1):43-53. [Medline]. [medscape.com]
It is currently not possible to estimate reliably the prevalence of Loeys–Dietz syndrome in a population because of the lack of large-scale epidemiological studies. [journals.eco-vector.com]
Pathophysiology
The clinical characteristics, molecular findings and pathophysiological mechanisms are summarized. The discovery of this entity has confirmed a key role for transforming growth factor beta signaling in aortic aneurysmal disease. [insights.ovid.com]
Morris Curr Opin Cardiol. 2015 Nov; 30(6): 587–59 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624847/ ■ Overexpression of Gremlin-1 in patients with Loeys-Dietz syndrome: implications on pathophysiology and early disease detection Jasmin Wellbrock, [internetmedica.com.br]
Familial thoracic aortic aneurysm/dissection with patent ductus arteriosus: genetic arguments for a particular pathophysiological entity. Eur J Hum Genet. 2004;12:173–80. [ncbi.nlm.nih.gov]
Primary intracerebral hemorrhage: pathophysiology. Can J Neurol Sci. 2005 Dec. 32 Suppl 2:S3-12. [Medline]. Thrift AG, Donnan GA, McNeil JJ. Epidemiology of intracerebral hemorrhage. Epidemiol Rev. 1995. 17(2):361-81. [Medline]. [medscape.com]
The pathophysiology of TAAD is complex and multi-factorial. [bmcmedgenet.biomedcentral.com]
Prevention
Prevention Can you prevent Loeys-Dietz syndrome? If you have the gene change that causes Loeys-Dietz syndrome, you may want to meet with a genetic counselor. [my.clevelandclinic.org]
At 12.5 years, the younger sister died due to aortic dissection (SV, 49mm; z-score,+7.3); she had previously declined a preventative intervention. [revespcardiol.org]
These aneurysms require careful monitoring and early surgical repair to prevent this severe complication. [childrenshospital.org]
There’s no cure for the disorder, so treatment is aimed at preventing and treating symptoms. Due to the high risk of rupture, someone with this condition should be followed closely to monitor the formation of aneurysms and other complications. [healthline.com]
Also, the prognosis for people with LDS has improved over the years because of better recognition and preventative aortic surgery for enlargement of the aorta and branches. [gentacalliance.org]