SNP Shot: Genomic Insights

Ehlers-Danlos syndrome (EDS) refers to a group of inherited disorders impacting connective tissues. These tissues provide structure and support to skin, bones, blood vessels, and other organs. EDS results from defects in these connective tissues, leading to a wide range of symptoms. These can vary from mildly loose joints to severe, potentially life-threatening complications.

The classification of EDS has evolved over time. Initially, there were 11 types, identified by Roman numerals (e.g., type I, type II). In 1997, a revised, simpler system called the Villefranche nomenclature reduced the number of types to six. These were given descriptive names based on their primary characteristics. The classification was updated again in 2017 to include rarer forms of EDS discovered more recently. The current (2017) classification recognizes 13 distinct types of EDS.

Hypermobility, or an unusually large range of joint motion, is common in many EDS types and is a defining feature of hypermobile EDS (hEDS). Infants and children with hypermobility often exhibit hypotonia, or weak muscle tone. This can delay the development of motor skills like sitting, standing, and walking. The loose joints are often unstable, leading to dislocations and chronic pain. A specific type, arthrochalasia EDS, is characterized by hypermobility and hip dislocations present at birth.

Many individuals with EDS have soft, velvety skin that is highly elastic (stretchy) and fragile. Easy bruising is common. Some types of EDS also cause abnormal scarring. People with classical EDS may experience wounds that split open easily with minimal bleeding. These wounds often leave scars that widen over time, creating distinctive "cigarette paper" scars. Dermatosparaxis EDS is marked by loose, sagging, and wrinkled skin, potentially with extra folds.

Bleeding problems are prevalent in vascular EDS (vEDS) due to the unpredictable tearing (rupture) of blood vessels and organs. These ruptures can lead to easy bruising, internal bleeding, intestinal perforation, or stroke. Women with vEDS are at risk of uterine rupture during pregnancy. Blood vessel rupture can also occur in kyphoscoliotic, classical, and classical-like EDS.

Other EDS types present with distinct signs and symptoms. Cardiac-valvular EDS affects the heart valves, causing severe problems with blood flow regulation. Kyphoscoliotic EDS involves severe spinal curvature that worsens over time, potentially affecting breathing due to restricted lung expansion. Brittle cornea syndrome, another EDS type, is defined by a thin cornea and other eye abnormalities. Spondylodysplastic EDS is characterized by short stature and skeletal abnormalities, such as bowed limbs. Musculocontractural and myopathic EDS types exhibit muscle abnormalities, including hypotonia and permanently bent joints (contractures). Periodontal EDS affects the teeth and gums.

Inheritance:

The inheritance pattern of EDS varies depending on the specific type. Classical, vascular, arthrochalasia, periodontal, and likely hypermobile EDS, typically follow an autosomal dominant pattern. This means that only one copy of the mutated gene is needed to cause the disorder. In some instances, the altered gene is inherited from an affected parent. In other cases, it arises as a new (de novo) mutation in individuals with no family history of the condition. Classical-like, cardiac-valvular, dermatosparaxis, kyphoscoliotic, spondylodysplastic, and musculocontractural EDS, as well as brittle cornea syndrome, are inherited in an autosomal recessive manner. Autosomal recessive inheritance requires two copies of the mutated gene, one from each parent. The parents are usually carriers, meaning they have one copy of the altered gene but don't display the disorder's signs or symptoms. Myopathic EDS can have either an autosomal dominant or autosomal recessive inheritance pattern.