about heritable connective tissue disorders

HCTDs

Overview

Heritable connective tissue disorders (HCTDs) are a group of genetic conditions affecting the body’s connective tissues. Connective tissue provides the support and structure to other tissue and organs in the body. HCTDs are multisystemic conditions, as such the presentation can vary between individuals, and individually across the lifespan. 

Due to the multisystem nature of HCTDs all organ systems can be impacted, this includes the skin, bones, joints, eyes, heart, and blood vessels. 

Common HCTDs

Ehlers-Danlos Syndromes (EDS):

• Cause: Mutations in genes affecting collagen production and processing
• Characteristics: Hyperelastic skin, generalised hypermobility, easy bruising, and chronic pain. There are 13 subtypes, including classical, hypermobile, and vascular EDS
• Management: Physical therapy, pain management, and careful monitoring of cardiovascular health, particularly in vascular EDS

Marfan Syndrome:

• Cause: Mutations in the FBN1 gene primarily
• Characteristics: Tall stature, long limbs, arachnodactyly (long fingers), scoliosis, chest deformities, lens dislocation, and aortic aneurysms
• Management: Regular cardiovascular monitoring, eye examinations, and surgical interventions when necessary

Loeys-Dietz Syndrome:

• Cause: Mutations in the TGFBR1 or TGFBR2 genes
• Characteristics: Arterial tortuosity, aortic aneurysms, craniofacial abnormalities, and skeletal malformations
• Management: Cardiovascular monitoring, surgical interventions, and genetic counselling

Stickler Syndrome:

• Cause: Mutations in the COL2A1, COL11A1, or COL11A2 genes
• Characteristics: Myopia, retinal detachment, hearing loss, cleft palate, and joint problems
• Management: Regular eye and hearing evaluations, surgical correction of cleft palate, and joint care

Diagnosis, Management  & Monitoring

Diagnosis for many living with HCTD can be a long and difficult journey, a journey that often earns the label of being a ‘diagnostic odyssey’. An odyssey that can be reflected in length, and influenced by many socioeconomic determinants of health, leading to healthcare access that sadly isn’t always equitable.

A HCTD can take a decade or more to be correctly diagnosed. Despite this, early diagnosis is critical to improved outcomes in quality of life, in part due to a reduced incidence of injury, and earlier detection of complications due to more comprehensive and timely surveillance being made available.

Improvements to care coordination across the board are noted with a diagnosis. 

There are many positive benefits to individual mental health that also come from timely diagnosis, this may be due to a reduction in traumatic medical event and interactions.  

Diagnosis:

• Genetic Testing: Identifies specific mutations responsible for the disorders. Genetic testing is available for all with the exception of hypermobile spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS)
• Clinical Evaluation: Detailed patient history, physical examination, and review of family history should form part of the dianostic process when HCTD is being considered and / or suspected

Management:

Long-term management of HCTD must be coordinated, collaborative, comprehensive and most importantly multi-disciplinary. 

• Multidisciplinary Approach: Involves specialists in genetics, cardiology, orthopaedics, ophthalmology, and other fields to include; pain specialists, neurology, surgeons and immunology
• Regular Monitoring: Cardiovascular health, skeletal integrity, and ocular health are areas of high importance
• Supportive Therapies: Physical therapy, occupational therapy, and pain management to improve quality of life
• Surgical Interventions: Necessary for severe complications like aortic aneurysms or severe scoliosis and spinal instabilities

Genetic Counselling  & Family Planning:

• Genetic Counselling: Provides patients and their families with information about the inheritance patterns, risks of recurrence in future pregnancies, and the implications of the disorder. Some further information on genetic counselling can be found on the Genetic Alliance Australia and The Rare Portal Websites
• Prenatal Testing: Provides options for families who wish to understand the genetic status of their offspring

Lifelong Management:

Long-term management of HCTDs requires a proactive and individualised approach across the lifespan. This must be person-centred at each and every step.

Essential components of this will give consideration to (individual needs based).

• Regular monitoring 
• Medical and surgical interventions 
• Education of appropriate lifestyle modifications
• Psychosocial assessment and supports identified 

Proper and active care coordination among healthcare providers, patients, and their families is crucial to optimise outcomes and enhance the quality of life for individuals with these complex disorders.

References

1. National Academies of Sciences, Engineering, and Medicine. Selected heritable disorders of connective tissue and disability. Washington, DC: The National Academies Press; 2022. DOI 10.17226/26431. 
2. Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 International Classification of the Ehlers–Danlos Syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. DOI 10.1002/ajmg.c.31552 
3. Halverson CME, Penwell HL, Francomano CA. Clinician-associated traumatization from difficult medical encounters: Results from a qualitative interview study on the Ehlers-Danlos Syndromes. SSM Qualitative Research in Health. Available online 2023;Feb DOI 10.1016/j.ssmqr.2023.100237
4. Rare Voices Australia RARE Portal Information https://rareportal.org.au/list-of-heritable-connective-tissue-disorders-hctd/