I’d like to share how a "typical" clinic day goes for the patients that are referred to my adult genetic medicine practice.
Our first patient is our only return visit of the day and is a 54-year-old man with longstanding intellectual disability of unknown cause. Intellectual disabilities affect 1%-3% of persons and 10% of all families and represent a major public health problem. A significant proportion of cases are presumed to be genetic in etiology, although until relatively recently only a few (roughly 5%) could be diagnosed. Although children with intellectual problems are often evaluated by a comprehensive battery of testing, many adults are not evaluated, or were evaluated in the distant past.
Dr. Matthew R. G. Taylor
A recent study (Genet. Med. 2010;12:32-8) in adults with unexplained intellectual disabilities found genetic diagnoses in more than 20% of patients and, while curative treatments are typically not possible, the value of a specific diagnosis to the patient’s family and the potential to access additional medical and social services with a confirmed diagnosis often make these investigations worthwhile. The recent development of X-linked "mental retardation" genetic panels that target men with intellectual disabilities will likely increase the diagnostic yield in this area.
Our second patient is a healthy 30-year-old man whose nephew was recently diagnosed with two genetic conditions: DiGeorge syndrome and I-cell disease. The patient and his wife, both present, want to know how this might affect their future children. We spend the first portion of the visit confirming the genetic and laboratory data surrounding the nephew’s unfortunate diagnoses. DiGeorge syndrome, which is caused by loss of genetic material from chromosome 22, is relatively common (1:4,000 infants), and frequently is identified because of cardiac defects, facial dysmorphisms, and learning difficulties. Milder cases might be missed in childhood and can present in adults as hypocalcemia, learning problems, and even schizophrenia. Only 10% of cases are inherited and our medical evaluation and physical exam did not turn up anything suspicious. We reassure the patient that his future children are at low risk for DiGeorge syndrome. I-cell disease, far less common (1:100,000), is unrelated to the DiGeorge diagnosis, but is uniformly fatal. We provide separate counseling for the I-cell risk and arrange for genetic testing to see if our patient is a carrier of an I-cell defect. If he is, his wife will then undergo carrier testing.
Our next patient is a 40-year-old woman with a history of joint hypermobility, chronic joint dislocations, easy bruising, and stretchy skin. Formerly very physically active, she had some pelvic symphysis separation during her last pregnancy and is now unable to work because of chronic pain. This constellation of symptoms represents one of the more-common referrals to adult medical geneticists. Our clinical evaluation confirms that she has a hypermobility syndrome, and we provide recommendations on how to best manage her pain and on a physical therapy regimen designed to improve her muscle tone and reduce the chance of future injuries.
Just before lunch, we have a heartbreaking visit with a 24-year-old woman who, accompanied by her partner and their young daughter, learns of her positive results for Huntington’s disease. At age 24 years, she has no overt symptoms, but the implications of the results are not lost on her as she cared for her grandparent who died from the disease. Furthermore, a psychiatric disorder in her estranged mother is now acknowledged as probable Huntington’s. The patient reveals to us that she is again pregnant and we have a long discussion about the potential risks to this pregnancy and what options she has to address this risk.
The afternoon begins with a full room; a 27-year-old man with Phelan-McDermid syndrome brought in by his parents and two caregivers. Phelan-McDermid syndrome represents one of a growing class of genetic diagnoses that have been recognized and defined only in the past 5-10 years. Involving a slightly different region of chromosome 22 than DiGeorge syndrome, Phelan-McDermid syndrome features cognitive problems including absent speech in many cases. As the diagnosis is unfamiliar to most internists, the family asks for our help in bridging this knowledge gap by serving as a resource to the internist who will be coordinating the primary care for this young man. Since patients with Phelan-McDermid syndrome are generally medically healthy we broach the subject of what plans are in place for the likely possibility that he will outlive his parents.
As the day winds down, we see two cases in which management implications are at the forefront of the discussions. First a 40-year-old man with a lifelong diagnosis of Alport syndrome comes to see us because he needs assistance finding a suitable kidney donor. He had his first transplant more than a decade ago and is again requiring dialysis. His antibody status precludes most unrelated donors and the prime focus is on his sister who has a 50% chance of being an Alport carrier, which would render her unsuitable as a donor. Molecular genetic testing for X-linked Alport is now available in the United States and we make arrangements to use this to find his mutation and then hopefully exclude the mutation in his sister who is a willing donor.