Genotypic Categorization of Loeys-Dietz Syndrome Based on 24 Novel Families and Literature Data

Loeys-Dietz syndrome (LDS) is a connective tissue disorder first described in 2005 featuring aortic/arterial aneurysms, dissections, and tortuosity associated with craniofacial, osteoarticular, musculoskeletal, and cutaneous manifestations. Heterozygous mutations in 6 genes (TGFBR1/2, TGFB2/3, SMAD2/3), encoding components of the TGF-β pathway, cause LDS. Such genetic heterogeneity mirrors broad phenotypic variability with significant differences, especially in terms of the age of onset, penetrance, and severity of life-threatening vascular manifestations and multiorgan involvement, indicating the need to obtain genotype-to-phenotype correlations for personalized management and counseling. Herein, we report on a cohort of 34 LDS patients from 24 families all receiving a molecular diagnosis. Fifteen variants were novel, affecting the TGFBR1 (6), TGFBR2 (6), SMAD3 (2), and TGFB2 (1) genes. Clinical features were scored for each distinct gene and matched with literature data to strengthen genotype-phenotype correlations such as more severe vascular manifestations in TGFBR1/2-related LDS. Additional features included spontaneous pneumothorax in SMAD3-related LDS and cervical spine instability in TGFB2-related LDS. Our study broadens the clinical and molecular spectrum of LDS and indicates that a phenotypic continuum emerges as more patients are described, although genotype-phenotype correlations may still contribute to clinical management.

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A Newly Discovered Genetic Disorder Associated With Life-Threatening Aortic Disease in a 6-Year-Old Boy

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620909234 ◽

2020 ◽

Vol 8 ◽

pp. 232470962090923

Author(s):

Mohanad Hamandi ◽

Madison L. Bolin ◽

Joy Fan ◽

Allison T. Lanfear ◽

Seth K. Woolbert ◽

...

Keyword(s):

Connective Tissue ◽

Genetic Disorder ◽

Aortic Disease ◽

Connective Tissue Disorder ◽

Aortic Aneurysms ◽

Gene Variation ◽

Life Threatening

Aortic aneurysms in children are rare and when present are usually caused by a connective tissue disorder. In this article, we present a case of multiple aortic aneurysms in an adolescent with a novel finding of a gene variation that is associated with aortic disease.

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Rheumatoid Arthritis Patient Presenting for a Total Knee Replacement

Anesthesiology: A Problem-Based Learning Approach ◽

10.1093/med/9780190850692.003.0027 ◽

2018 ◽

pp. 237-239

Author(s):

Perin Kothari ◽

Sree Kolli

Keyword(s):

Rheumatoid Arthritis ◽

Cervical Spine ◽

Rheumatoid Arthritis Patient ◽

Connective Tissue ◽

Preoperative Assessment ◽

Connective Tissue Disorder ◽

Multiple Organ ◽

Organ Systems ◽

Intraoperative Management ◽

Total Knee

Rheumatoid arthritis (RA) is a progressive connective tissue disorder. Patients with RA have several concerns relevant to the anesthesiologist. RA can affect multiple organ systems beyond simply the joints. A thorough history and physical is needed to evaluate for cardiac, respiratory, and neurologic abnormalities. Furthermore, cervical spine involvement is very common for patients with RA. Special consideration is needed for airway management of these patients. In addition, radiographic imaging may be helpful in evaluating the extent of the disease. Regional and neuraxial anesthesia may be alternatives to general anesthesia in patients with RA when possible. This chapter discusses preoperative assessment and intraoperative management of patients with RA.

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General Anaesthesia in a Child with Larsen Syndrome

Anaesthesia and Intensive Care ◽

10.1177/0310057x0303100216 ◽

2003 ◽

Vol 31 (2) ◽

pp. 217-220 ◽

Cited By ~ 6

Author(s):

L. A. H. Critchley ◽

L. Chan

Keyword(s):

Cervical Spine ◽

General Anaesthesia ◽

Laparoscopic Hernia Repair ◽

Connective Tissue Disorder ◽

Facial Appearance ◽

Respiratory Complications ◽

Cervical Spine Instability ◽

Larsen Syndrome ◽

Potential Problems ◽

Postoperative Respiratory Complications

Larsen syndrome is a rare congenital connective tissue disorder which is characterized by multiple dislocations of major joints, typical facial appearance, cervical spine narrowing and instability and respiratory difficulties secondary to laryngotracheomalacia. A case of general anaesthesia for laparoscopic hernia repair in a male child aged 16 months with this syndrome is presented. Anaesthesia was well tolerated though intubation proved difficult. Cervical spine instability and postoperative respiratory complications are potential problems.

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Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome

Genes ◽

10.3390/genes10020128 ◽

2019 ◽

Vol 10 (2) ◽

pp. 128

Author(s):

Louise Benarroch ◽

Mélodie Aubart ◽

Marie-Sylvie Gross ◽

Pauline Arnaud ◽

Nadine Hanna ◽

...

Keyword(s):

Marfan Syndrome ◽

Age Of Onset ◽

Expression Profiles ◽

Phenotypic Variability ◽

Surrogate Endpoint ◽

Connective Tissue Disorder ◽

Clinical Variability ◽

Fbn1 Gene ◽

Adventitial Fibroblasts ◽

Alternatively Spliced

Marfan syndrome (MFS) is a rare connective tissue disorder mainly due to mutations in the FBN1 gene. Great phenotypic variability is notable for age of onset, the presence and absence, and the number and the severity of the symptoms. Our team showed that FBN1 gene expression level was a good surrogate endpoint for severity of some MFS clinical features. Eight alternative transcripts are referenced for the FBN1 gene. We hypothesized that MFS clinical variability could be related to specific FBN1 isoforms. Isoform expression profiles were investigated in skin and adventitial fibroblasts from controls and MFS patients. The results of the study showed that, in skin and adventitial fibroblasts, only three isoforms were found: FBN1_001, FBN1_004, and FBN1_009. The main isoform was FBN1_001 and it was significantly reduced in skin and adventitial fibroblasts of MFS patients. The expressions of FBN1_004 and FBN1_009 isoforms were similar between controls and MFS patients. However, the expression of the three isoforms was correlated only in patients. Furthermore, their expression levels were associated with the presence of ectopia lentis in MFS patients. Therefore, our results highlight that the two minor alternatively spliced FBN1 isoforms play a possible role in the pathogenesis of the disease.

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Osteopetrosis in a Patient of Systemic Sclerosis Sine Scleroderma: A Rare Association

Indian Journal of Radiology and Imaging ◽

10.1055/s-0041-1740506 ◽

2022 ◽

Author(s):

Saroj K. Pati ◽

Praveen Raja ◽

Ajoy K. Behera ◽

T.G. Ranganath ◽

Narendra K. Bodhey

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Male Patient ◽

Connective Tissue Disorder ◽

Unknown Etiology ◽

Cutaneous Manifestations ◽

Rare Association ◽

Serologic Markers ◽

Chief Complaints ◽

Musculoskeletal Systems

AbstractSystemic sclerosis is a connective tissue disorder of unknown etiology. Although it is a multisystemic disorder, skin thickening is considered as a hallmark of the disease. It usually involves the lungs, gastrointestinal, and musculoskeletal systems. However, a rare subset of systemic sclerosis, systemic sclerosis sine scleroderma, is characterized by internal organ involvement and positive serologic markers with the total or partial absence of cutaneous manifestations. We present a rare association of osteopetrosis in a case of systemic sclerosis sine scleroderma, in a 22-year-old male patient, who presented with pulmonary symptoms as his chief complaints, unreported so far in literature.

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Transarterial coil embolization of an aortic root pseudoaneurym in a patient with Loeys-Dietz syndrome: a case report

CVIR Endovascular ◽

10.1186/s42155-020-00184-5 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Robert D’Ortenzio ◽

Leandro Cardarelli-Leite ◽

Ravjot Dhatt ◽

Jacqueline Saw ◽

Manraj Heran

Keyword(s):

High Risk ◽

Connective Tissue ◽

Aortic Root ◽

Coil Embolization ◽

Surgical Intervention ◽

Connective Tissue Disorder ◽

Case Presentation ◽

Standard Management ◽

Anastomotic Pseudoaneurysm ◽

Arterial Aneurysms

Abstract Background Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder characterized by arterial aneurysms and vascular friability. Surgical intervention for LDS patients carries significant morbidity and mortality. Currently, the standard management of aortic root pseudoaneurysms is surgical intervention. Case presentation A 20 year old male with LDS presented with a progressively enlarging ascending aortic aneurysm. He underwent a Bentall-type aortic root replacement complicated by a 20 mm aortic root anastomotic pseudoaneurysm. Due to the patient’s high risk for repeat surgical intervention, he underwent successful transarterial coil embolization of his aortic root pseudoaneurysm without complication. Conclusions Coil embolization may provide an alternative treatment for patients presenting with aortic root pseudoaneurysm who are high risk for traditional surgical treatment, such as those with connective tissue disease.

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