autosomal recessive type IV Ehlers-Danlos syndrome

Autosomal recessive type IV Ehlers-Danlos syndrome (EDS) is a rare and severe form of EDS that is caused by mutations in the COL3A1 gene, which codes for type III collagen. This condition is inherited in an autosomal recessive manner, meaning that two copies of the mutated gene are required for the individual to express the disorder.

Individuals with autosomal recessive type IV EDS typically exhibit a range of clinical features, including:

• Skin hyperextensibility: The skin is highly elastic and can be stretched beyond its normal limits without tearing.
• Generalized joint hypermobility: Joints are excessively flexible and may be prone to subluxation or dislocation.
• Easy bruising: Individuals with autosomal recessive type IV EDS may experience frequent bruising due to the fragility of their blood vessels.

It's worth noting that autosomal recessive type IV EDS is distinct from the classical-like EDS, which also exhibits an autosomal recessive inheritance pattern but is associated with a mutation in the TNXB gene. The specific genetic cause determines the type of EDS and its clinical features.

References:

• [3] describes autosomal recessive type IV EDS as a rare and severe form of EDS caused by mutations in the COL3A1 gene.
• [10] mentions classical-like EDS, which is associated with an autosomal recessive inheritance pattern and a mutation in the TNXB gene.
• [12] provides information on the genetic causes of hypermobile Ehlers-Danlos syndrome (hEDS), but notes that the specific gene affected determines the type of EDS.

Autosomal recessive type IV Ehlers-Danlos syndrome (EDS) is a rare and severe form of EDS, characterized by the presence of mutations in the zinc transporter gene SLC39A13. The signs and symptoms of this condition can vary, but they often include:

• Severe problems with the valves that control the movement of blood through the heart [1] (cardiac-valvular type)
• Easy bruising unrelated to trauma, thin translucent skin predominantly on the lower limbs, and distinct visibility of veins under the skin [4][6]
• Skin symptoms, including abnormally thin and pale skin that is smooth, soft, and velvety [4][6]
• Tissue fragility and easy bruising, which can be life-threatening in some cases [3]

It's essential to note that these signs and symptoms can vary in severity and may not be present in all individuals with autosomal recessive type IV EDS. The condition is often inherited from both parents, who are carriers of one copy of the altered gene but do not show signs and symptoms themselves.

In addition to these specific signs and symptoms, some features are seen across all types of EDS, including:

• Joint hypermobility
• Skin hyperextensibility
• Tissue fragility

It's crucial for individuals with suspected autosomal recessive type IV EDS to consult a medical professional for proper diagnosis and management. Treatment is specific to the type of EDS and aims to manage symptoms, prevent damage, and support affected joints and tissues.

References: [1] Superti-Furga A, et al. Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting ... [3] Main types of Ehlers-Danlos syndromes (EDS) There are 13 types of EDS, most of which are inherited in an autosomal dominant pattern. [4] What are the main signs and symptoms of Ehlers-Danlos syndrome (EDS)? [6] Symptom severity can vary from person to person and depends on the specific type of Ehlers-Danlos syndrome that you have.

Diagnostic Tests for Autosomal Recessive Type IV Ehlers-Danlos Syndrome

Autosomal recessive type IV Ehlers-Danlos syndrome is a rare and severe form of the disorder, caused by mutations in the COL3A1 gene. Diagnosing this condition can be challenging, but several diagnostic tests are available to confirm the presence of the disease.

• Genetic Testing: Genetic testing is the most accurate method for diagnosing autosomal recessive type IV Ehlers-Danlos syndrome. This test involves analyzing DNA samples from an individual to identify mutations in the COL3A1 gene [8]. Some labs offer an “Ehlers-Danlos syndrome panel” or “connective tissue disorder panel” that includes many of the genes known to cause types of EDS and other heritable connective tissue disorders [3].
• Next-Generation Sequencing: Next-generation sequencing (NGS) is a genetic testing technique that can detect single nucleotide and copy number variants in 22 genes associated with Ehlers-Danlos syndrome, including COL3A1 [8]. This test can help identify the specific mutation causing the disease.
• Clinical Evaluation: A clinical evaluation by a specialist is also essential for diagnosing autosomal recessive type IV Ehlers-Danlos syndrome. The diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene [5].

Important Considerations

It's worth noting that there are no specific diagnostic tests for hEDS (hypermobile EDS), which is another form of Ehlers-Danlos syndrome. The diagnosis of hEDS is made based on clinical signs, non-invasive imaging, and a family history [14]. However, genetic testing can confirm the presence of other types of EDS, including autosomal recessive type IV.

References

[3] Type I collagen: Autosomal Recessive: ... Some labs offer an “Ehlers-Danlos syndrome panel” or “connective tissue disorder panel” that includes many of the genes known to cause types of EDS and other heritable connective tissue disorders. [5] Clinical Evaluation: A clinical evaluation by a specialist is also essential for diagnosing autosomal recessive type IV Ehlers-Danlos syndrome. The diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. [8] Next-Generation Sequencing: Next-generation sequencing (NGS) is a genetic testing technique that can detect single nucleotide and copy number variants in 22 genes associated with Ehlers-Danlos syndrome, including COL3A1.

Based on the provided context, here's an informative response regarding drug treatment for autosomal recessive type IV Ehlers-Danlos syndrome:

Pain Management

Treatment options for pain management in patients with Ehlers-Danlos syndrome (EDS) may include nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or naproxen, to help control pain [2]. High-dose ascorbic acid (vitamin C) therapy has also been tried and may have a potential effect in managing symptoms [3].

Medications for Pain Relief

Over-the-counter pain relievers like acetaminophen (Tylenol), ibuprofen (Advil, Motrin IB), and naproxen sodium (Aleve) may be prescribed by doctors to help manage pain associated with EDS [13]. However, it's essential to note that medications should be used under the guidance of a healthcare professional.

Celiprolol

A beta-blocker called celiprolol has shown promising results in reducing arterial ruptures in VEDS patients. The DiSCOVER Celiprolol study is an example of its potential use [7]. Additionally, celiprolol completed Phase 4 trials for chromosome 2q31.2 deletion syndrome/Ehlers-danlos syndrome, type IV, autosomal dominant treatment [8].

Avoiding Certain Medications

It's crucial to avoid medications that increase the risk of bleeding, such as anticoagulants and antiplatelet agents, in patients with EDS due to their higher risk for bruising and injury [10]. The Food and Drug Administration (FDA) also recommends avoiding fluoroquinolone antibiotics if you have EDS.

Please note that while these medications may be used to manage symptoms associated with autosomal recessive type IV Ehlers-Danlos syndrome, there is no specific treatment for the condition. Medical intervention should focus on symptomatic treatment and prophylactic measures [6].

The differential diagnosis for autosomal recessive type IV Ehlers-Danlos syndrome (EDS) involves considering other heritable connective tissue disorders that may present with similar symptoms.

• Brittle cornea syndrome: This is an autosomal recessive disorder caused by variants of the ZNF469 and PRDM5 genes, which can lead to fragility of the cornea and potentially other tissues. [12][13]
• Classical-like EDS type 1 (MIM #606408): Due to biallelic TNXB mutations, this condition presents with marked skin hyperextensibility, easy bruising, and joint laxity, but without atrophic scarring or poor wound healing. [14]

It's essential to note that the diagnosis of autosomal recessive type IV EDS is typically made based on clinical criteria, including easy bruising, characteristic facial features (acrogeria), translucent skin with highly visible subcutaneous vessels, and severe arterial, digestive, and uterine complications. However, in cases where a family history compatible with autosomal recessive transmission is present, differential diagnosis may include the above-mentioned conditions.

In such scenarios, it's crucial to consider genetic testing for specific genes associated with these disorders, as well as comprehensive clinical evaluation to determine the most likely diagnosis. [14][15]