Case report details process to identify long-unknown cause of patient’s severe intellectual disability with microcephaly
The New York State Office for People With Developmental Disabilities (OPWDD) today announced the publication of a case report from OPWDD’s Institute for Basic Research in Developmental Disabilities (IBR) describing the genetic cause of an adult patient’s lifelong, severe intellectual disability. The process consisted of cutting-edge genetic analysis techniques, combined with review of the patient’s 40-year clinical history, providing an extensive longitudinal history and a functional status update.
The 42-year-old female patient has severe intellectual disability, autism spectrum disorder, microcephaly, hypotonia, seizures, and self-injurious behavior. Her clinical history included evidence of developmental delays, ophthalmologic findings, and impairments in speech and adaptive functioning. Her parents had first observed her developmental delays when she was an infant but, despite the decades of extensive testing and consultations with many specialists that followed, no single underlying cause had been found for her combination of symptoms.
The care team at OPWDD’s Jervis Clinic on Staten Island recently arranged for trio whole exome sequencing (WES), a genetic test used to evaluate patients with unexplained rare genetic conditions by comparing the DNA of the patient and her parents for genetic changes that might explain the condition. The test identified a small de novo mutation in the KIF11 gene, meaning that it was not inherited from either of the patient’s parents. This gene provides instructions for the KIF11 protein to help cells divide properly, including cells in the developing brain and eyes.
Mutations in the KIF11 gene are known to cause MCLID (microcephaly, chorioretinopathy, lymphedema, and intellectual disability) syndrome, a rare condition which can include microcephaly, eye and retina problems, and intellectual disability, all of which were present in the patient. Thus, the patient’s condition was identified as KIF11-related MCLID syndrome. Because most of what was previously known about this syndrome pertained to affected children, long-term information about affected adults was limited. By piecing together the patient’s medical and developmental history from infancy, including a detailed account from her mother, researchers were able to document how her symptoms evolved over more than 40 years, resulting in a detailed, long-term picture of how the syndrome can affect people throughout their lifespan.
The case report’s authors said that this case suggests that adults diagnosed with unexplained developmental disabilities before genetic testing became widely available may benefit from newer whole exome sequencing testing that is available today. A precise diagnosis can guide medical care and help families learn more about their conditions, including genetic testing and family planning considerations.
The patient’s care team was led by psychiatrist-researcher Gholson J. Lyon, MD, PhD, of IBR’s George A. Jervis Clinic and Department of Human Genetics, and included Clinic colleagues Ruhi Shah, MS, MPH, CGC, and Karen Amble, LMSW. Department colleagues included Thrishna Chathurvedula, Juvy Rabelas, Kareem Touleimat, and Elaine Marchi, MS. Shaydah Kheradmand, MS, of GeneDX, Gaithersburg, MD, and Kuldeep Singh, MD, of the Zucker School of Medicine at Hofstra/Northwell, Staten Island, NY, also contributed. The case report was published in the article, “An Adult Presentation of KIF11-Related MCLID Syndrome: Case Report and 40-Year Follow-Up,” in the American Journal of Medical Genetics Part A.
New York State Office for People With Developmental Disabilities Commissioner Willow Baer said, “Receiving a genetic diagnosis can be very helpful to patients and families, even decades after the first appearance of symptoms. Under Governor Hochul’s leadership, OPWDD’s Institute for Basic Research has received significant investments to modernize its lab and bring genomic sequencing to more New Yorkers, making important discoveries like these more likely in the future.”
“Following this patient for so many years has helped us see the full picture of how this rare condition develops over a lifetime,” said Dr. Jill Pettinger, Deputy Commissioner for Statewide Services at OPWDD. “We are grateful to the patient’s family for sharing their experience, which may help other patients and families get answers sooner.”
Funding for this report was provided by the George A. Jervis Clinic of the New York State Institute for Basic Research in Developmental Disabilities of the New York State Office for People With Developmental Disabilities.
About OPWDD and IBR
The Institute for Basic Research in Developmental Disabilities (IBR) is the research arm of the New York State Office for People With Developmental Disabilities (OPWDD). IBR also provides clinical services and conducts educational programs. OPWDD is responsible for coordinating services for New Yorkers with developmental disabilities, including intellectual disabilities, cerebral palsy, Down syndrome, autism spectrum disorders, Prader-Willi syndrome, and other neurological impairments.