Ehlers-Danlos Syndromes (EDS) are inherited disorders impacting the body’s connective tissues. These tissues provide support and structure to skin, bones, blood vessels, and organs. Understanding how EDS is passed through families can be complex, leading many to wonder if the condition can seemingly “skip” a generation. This article explores the genetic intricacies of EDS inheritance and clarifies why it might appear to bypass family members.
Understanding Ehlers-Danlos Syndromes
Ehlers-Danlos Syndromes (EDS) are a diverse group of conditions affecting connective tissue, which is largely made of proteins like collagen. This tissue provides strength and elasticity to various structures. Defects in the production or processing of collagen weaken these tissues.
The weakened connective tissue can lead to various symptoms. Common manifestations include joint hypermobility (joints extend beyond their typical range of motion) and skin hyperextensibility (unusually stretchy skin). Tissue fragility, leading to easy bruising and poor wound healing, is another characteristic feature. There are currently 13 recognized types of EDS, each with distinct genetic causes and clinical features, although some symptoms overlap across types.
How Ehlers-Danlos Syndromes Are Inherited
Ehlers-Danlos Syndromes are genetic conditions, resulting from gene mutations. These gene mutations are typically inherited from parents. The way EDS is passed down depends on the specific type of the syndrome. Most forms follow either an autosomal dominant or an autosomal recessive inheritance pattern.
In autosomal dominant inheritance, only one altered copy of a specific gene is sufficient to cause the disorder. For each child of a parent with an autosomal dominant form of EDS, there is a 50% chance of inheriting the altered gene and therefore developing the condition. Classical EDS, hypermobile EDS (hEDS), and vascular EDS (vEDS) are examples of types commonly inherited in an autosomal dominant manner.
Autosomal recessive inheritance requires two altered copies of a specific gene for the disorder to manifest. Parents who carry one copy of the altered gene but do not have the condition themselves are known as carriers. If both parents are carriers of the same autosomal recessive mutation, each child has a 25% chance of inheriting two altered gene copies and developing the condition. Kyphoscoliotic EDS (kEDS) and dermatosparaxis EDS (dEDS) are typically inherited in an autosomal recessive pattern.
Why Ehlers-Danlos Syndromes Can Appear to Skip a Generation
While Ehlers-Danlos Syndromes are inherited genetically and do not truly “skip” generations, they can appear to do so due to several complex factors. A key reason is variable expressivity. This phenomenon means that individuals carrying the same genetic mutation can experience a wide range of symptoms, differing in both type and severity. For example, one family member might have severe joint dislocations and skin fragility, while another with the identical genetic change might only exhibit mild joint hypermobility, making their condition less noticeable.
Incomplete penetrance also contributes to the illusion of skipping a generation. This occurs when an individual carries a gene mutation associated with EDS but shows no observable symptoms of the condition. The gene is present, but its effects are not expressed, which can lead to a mistaken belief that the gene was not passed down. This can make tracing the condition through a family challenging without specific genetic testing.
New, or de novo, mutations can cause EDS to appear in a family with no prior history of the condition. In these instances, the genetic mutation arises spontaneously in the affected individual, rather than being inherited from either parent. Approximately 50% of individuals diagnosed with classical EDS have the disorder as a result of a de novo pathogenic variant. This unexpected appearance can create the impression that the condition has “skipped” previous generations.
Genetic Testing and Family Considerations
Genetic testing is useful in diagnosing specific types of Ehlers-Danlos Syndromes and clarifying inheritance patterns within families. For many types of EDS, identifying the underlying gene mutation can confirm a diagnosis. This information is valuable for affected individuals and their families.
While genetic testing can identify specific gene mutations for most EDS types, a genetic cause for hypermobile EDS (hEDS) has not yet been identified, meaning there is currently no genetic test for hEDS. In such cases, diagnosis relies on clinical criteria and physical examination. Genetic counseling is recommended for families concerned about EDS. Genetic counselors can provide information about inheritance risks for future generations, discuss carrier status, and help families navigate living with the condition.