Ehlers-Danlos Syndromes (EDS) are a group of inherited disorders affecting connective tissues, the support structures found throughout the body (skin, joints, blood vessels, and organs). These conditions arise from changes in genes responsible for producing or processing collagen and related proteins. This leads to symptoms like overly flexible joints, stretchy skin, and tissue fragility. When a child is diagnosed, families often wonder if the condition can skip a generation, particularly if the preceding parent appears unaffected. Understanding the genetic principles governing how EDS is passed down helps answer this question.
Understanding EDS Inheritance Patterns
The majority of EDS types, including the most common form, Hypermobile EDS (hEDS), follow an autosomal dominant pattern of inheritance. This means a person needs to inherit only one copy of the altered gene from either parent to have the condition. Under this pattern, a child of an affected parent has a 50% chance of inheriting the gene alteration, and the condition should theoretically appear in every generation. However, some rarer and more severe types, such as Kyphoscoliotic EDS, follow an autosomal recessive pattern.
Autosomal recessive inheritance requires a child to receive one altered gene copy from each parent to develop the disorder. Parents who each carry one copy of the altered gene are usually healthy and are known as asymptomatic carriers. For these recessive forms, the condition can genuinely skip generations, only reappearing when two carriers have a child together. The perception of skipping in the more prevalent autosomal dominant forms, however, is explained by other genetic mechanisms.
The Mechanism of Incomplete Penetrance
The concept that explains why a dominant EDS type might seem to skip a generation is incomplete penetrance. Penetrance refers to the likelihood that a person who has inherited the disease-causing gene alteration will show clinical signs of the condition. When penetrance is incomplete, an individual can carry the specific gene mutation but remain completely asymptomatic throughout their life.
This asymptomatic individual is still capable of passing the gene alteration to their children, who may then develop the full clinical syndrome. In the family’s medical history, the condition appears to jump from the grandparent to the grandchild, bypassing the parent. The gene was inherited by the parent, but for reasons not yet fully understood, it was not expressed. Possible factors influencing this lack of expression include the interaction with other genes or various environmental influences.
Variable Expression and Symptom Severity
Variable expression means that individuals who carry the same gene alteration and have the condition can experience vastly different types and degrees of symptoms. This differs from incomplete penetrance, which involves a complete lack of symptoms. Within the same family, one person might suffer from debilitating joint dislocations and chronic pain, while a close relative with the identical gene change might only have slightly hyperextensible skin or mild, occasional joint aches.
This wide range of severity often leads to the mistaken belief that a generation was skipped. A mildly affected parent may have symptoms so subtle or non-specific that they were never diagnosed, or their issues were attributed to general aging or sports injuries. Only when the condition manifests more severely in their child does the family realize the parent was affected. Both incomplete penetrance and variable expression contribute to the complex inheritance patterns observed in EDS families.
Confirming Genetic Status Through Testing
For many types of EDS, genetic testing is available to confirm whether a person carries a known gene alteration, even if they are currently asymptomatic. Tests can identify mutations, such as the COL3A1 gene for Vascular EDS or the COL5A1 and COL5A2 genes for Classical EDS. If a parent of an affected child is suspected of being an asymptomatic carrier, genetic sequencing can provide a definitive answer by identifying the specific mutation in their DNA.
However, the most common type, Hypermobile EDS (hEDS), remains a clinical diagnosis because the specific causative gene or genes have not yet been identified. For hEDS, diagnosis is based on physical examination and a thorough review of the patient’s symptoms and family history. Genetic counseling is a necessary step for families, as it helps in understanding the risks for future generations and provides guidance based on established clinical and inheritance patterns.