From the Research
A patient with both COL1A1 and TNXB homozygous mutations would most likely be classified as having a complex or overlapping form of Ehlers-Danlos syndrome (EDS) rather than fitting neatly into either classical or arthrochalasia types. This classification is based on the understanding that COL1A1 mutations are typically associated with arthrochalasia EDS, particularly when they affect the processing of type I collagen, as noted in a study published in 2022 1. Meanwhile, TNXB mutations are linked to a classical-like EDS phenotype with joint hypermobility, skin hyperextensibility, and easy bruising, as described in a 2017 study 2 and further characterized in a 2019 study 3.
When both mutations are present homozygously, the patient would likely exhibit features of both types, creating a more complex clinical picture. This complexity is underscored by a 2022 case report of a patient with a novel homozygous variant in the TNXB gene, presenting with rare neurological manifestations 4. Management would need to address the specific manifestations present, including joint stabilization, skin care, pain management, and cardiovascular monitoring. Genetic counseling would be essential, as would a multidisciplinary approach involving specialists in genetics, rheumatology, cardiology, and physical therapy. The presence of both mutations suggests a more severe phenotype requiring comprehensive care tailored to the patient's specific symptoms, as suggested by a study on the clinical and molecular characterization of classical-like Ehlers-Danlos syndrome due to a novel TNXB variant 3.
Key considerations in managing such a patient include:
- Genetic counseling to understand the implications of the mutations and the potential for passing them to offspring
- Multidisciplinary care to address the various systemic manifestations of the disease
- Regular monitoring for cardiovascular complications, given the association of EDS with vascular fragility and risk of rupture
- Pain management and physical therapy to maintain joint mobility and strength, while minimizing the risk of injury
- Skin care to prevent and manage easy bruising and potential skin tears
Given the rarity and complexity of this condition, a comprehensive and individualized approach to care is crucial, taking into account the latest research and guidelines, such as those outlined in a systematic review of Ehlers-Danlos syndrome type arthrochalasia published in 2022 1.