This is one in a series of blogs where I discuss different conditions manifesting autstic symptomatology of known origin or neuropathology (so-called syndromic autism). The first of these blogs was on tuberous sclerosis (http://bit.ly/17ExHYt ). The emphasis in all of these blogs is in the commonality of abnormalities in certain parts of the brain. It is my belief that in autism there is a common lesion that interferes in some way with the division of germinal cells early during brain development. The end result is abnormalities in cell migration and malformed areas of the cerebral cortex and brainstem. You can find additional information about this process at: http://bit.ly/1aM5KFu and http://bit.ly/136db0t In this blog I discuss the Ehlers-Danlos syndrome and some commonalities to idiopathic autism primarily in terms of brain pathology.
The Ehlers-Danlos syndrome (EDS) is a group of inherited conditions that affect the connective tissues of the body. As the name implies, connective tissue serves to “connect” or join together different parts of an organ. In doing so, connective tissue provides support to the organ and gives it its distinctive shape. Some specialized types of connective tissue, provide more than support, and play a significant functional role for the body, e.g., adipose or fat, cartilage, blood. Considering both the large variety of connective tissues and the fact that they can be found almost anywhere in the body, it is unsurprising that disorders of connective tissue are very common (think of anemia, arthritis, or even obesity).
There are over 200 recognized connective tissue disorders of multiple causation. Ehlers-Danlos syndrome belongs to a small group of connective tissue disorders that are genetic in origin. Other inherited connective tissue disorder that manifest autistic symptomatology include Marfan’s and the Lujan-Fryns syndromes. People with a Marfanoid physical appearance (i.e., tall with long extremities- see figure), absence of the corpus callosum and mental retardation usually have the Lujan-Fryns syndrome. Approximately 90% of patients with the Lujan-Fryns syndrome exhibit some type of mental symptomatology, the most common of which is autistic behaviors. Tantam et al. (1990) reported 3 cases of Asperger syndrome with a Marfanoid appearance. Some case reports mention patients with the dual diagnosis of Ehlers-Danlos syndrome and autism (Fehlow et al., 1993) and the relationship has been expanded upon in a communication by Sieg (1992). EDS and autism share comorbidities like irritable bowel syndrome (arguable), sensory integration disorders, and anxiety disorders.
In Ehlers Danlos syndrome a number of different mutations affect a protein called collagen. This is the most common protein found in the human body, accounting for 25 to 35% of the whole body protein. The gelatin used in the food industry is a type of collagen that has been altered in a chemical reaction with water.
Ehlers-Danlos syndrome is seen in approximately 1 out of every 5,000 people within the general population. It affects the connective tissue of the joints, blood vessels and skin providing for loose/flexible joints (as in double-jointed individuals), fragile blood vessels (bleeding) and stretchy skin that bruises easily. Symptoms vary in severity across patients. Some individuals, having a “vascular type” of the condition, may suffer from life threatening complications like spontaneous rupture of blood vessels and bowels.
People with EDS may have abnormal brain development because matrix proteins (as seen in germinal tissue) and those related to cell attachment are affected. Migrational abnormalities may be common with heterotopias (misplaced cluster of cells) being reported in some cases (Cupo et al., 1981). There are now several case reports in patients diagnosed with Ehlers-Danlos syndrome relating nodular brain heterotopia to seizures and dyslexia. Since neurons fail in their migration to the cortex, the same may be malformed, exhibiting patches of abnormal convolutions (polymicrogyria). The brainstem and cerebellum may also be affected and patients are usually born with portions of their cerebellum protruding through a large opening in the occipital bone (foramen magnum). This type of abnormality is called a Chiari type I malformation.
Figure: Clusters of cells fail in their migratory attempt out of the periventricular germinal zone and remain behind as nodules impinging on the wall of the ventricles (so-called candle gutterings). Similarities between this finding and that reported in autism can be judged from a coronal cut in a postmortem specimen shown in http://bit.ly/136db0t
In previous blogs we have mentioned how the proposed pathology for autism predisposes the same to cortical hyperexcitability. The explanation has been used to suggest a mechanism capable of explaining the presence of seizures, sensory problems and headaches. The analogy to migraine headaches was dealt in http://bit.ly/14h1THp It is therefore of interest the conclusions of a study: “Individuals with EDS may be prone to migraine due to an inherent disorder of cerebrovascular reactivity or cortical excitability” (Jacome, 1999).
In conclusion, Ehlers Danlos is another cause of syndromic autism. The pathology exhibited in the brains of individuals with EDS suggests a migratory defect of germinal cells early on during gestation. This is the same type of abnormality that we have proposed in idiopathic autism. This commonality among a very large number of conditions giving rise to syndromic autism seems more than a coincidence and deserves further investigation.
Cupo LN, Pyeretz R, Olson J, McPhee S, et al. Ehlers-Danlos syndrome with abnormal collagen fibrils, sinus of Valsalva aneurysms, myocardial infarction, panacinar emphysema and cerebral heterotopias. Am J Med 71:1051-1058, 1981.
Fehlow P, et al. Early infantile autism and excessive aerophagy with symptomatic magalocolon and ileus in a case of Ehlers-Danlos syndrome. Pediatric Grenzgeb 31:259-267, 1993.
Jacome DE. Headache in Ehlers Danlos syndrome. Cephalagia 19():781-6, 1999.
Sieg KG. Autism and Ehlers-Danlos syndrome. Journal of the American Academy of Child and Adolescent Psychiatry 31:173, 1992.
Tantam D. Evered C, Hersov L. Asperger’s syndrome and ligamentous laxity. Journal of the American Academy of Child and Adolescent Psychiatry 29:892-6, 1990.