In 1933, a Dutch pediatrician named Cornelia de Lange noticed several of her patients had similar symptoms of what’s now known as a multisystem disorder, a type of physical and cognitive development disorder which affects functioning in disparate areas. These patients had low birth weight, usually less than five pounds; gastroesophageal reflux disease; mild to severe developmental delays, particularly language delay; behavioral issues such as self-injury behaviors; thick eyebrows and long eyelashes; body hair; hearing and vision difficulties; and heart defects. Cornelia de Lange syndrome would prove to be a genetic condition, and it occurs in about one in 10,000 live births.
The primary culprit appears to be a gene called HDAC8, which is responsible for a protein called cohesin. The three functions of cohesin are to hold together identical chromosomes that belong together, to make sure chromosomes separate correctly during cell division, and to serve as a sort of spell check for DNA. Failure in the last function during embryonic development is believed to be a key factor in Cornelia de Lange syndrome. Replication failures at that early stage explain the broad variety of deficits and abnormalities at multiple sites.
Cohesin undergoes certain changes in the course of its duties. Normally, it is restored to its original state afterward, in a process called cellular recycling, so that it is available next time it’s needed. The mutations to HDAC8 believed to be associated with Cornelia de Lange syndrome and similar diseases called cohesinopathies interfere with cellular recycling and cause the cohesin complex to fail.
There is very little treatment available for most of the symptoms of Cornelia de Lange syndrome. Because it involves so many different areas and functions, treatment often requires the involvement of a team of professionals to address the developmental delays, digestive issues, neurological deficits, and other symptoms and effects of the condition. Many patients have a serious heart defect called tetralogy of Fallot, which often requires surgery.