Twins’ Different Symptoms Complicate Diagnosis
Juvenile Batten disease is difficult to diagnose promptly and accurately, as demonstrated by the case of twin girls with different symptoms of the same disorder.
The case suggests that a referral to a specialist should be made when a patient’s clinical picture doesn’t line up with their history, or when their signs and symptoms point toward multiple diagnoses.
The fraternal twins — meaning that two eggs were fertilized simultaneously — were conceived through in vitro fertilization (IVF) and showed normal results when screened as newborns.
At 9 months old, however, doctors noticed a heart murmur in one of the twins and referred her to a pediatric cardiologist. An echocardiogram revealed a narrow pulmonary valve connecting the heart to the arteries leading to the lungs, and a small opening between the heart’s upper chambers, known as a patent foramen ovale.
Although both girls met all developmental milestones by 12 months old, the twin with the heart defects had begun to fall behind by 18 months. She showed delayed speech, an abnormal gait, and hypersensitivity to sounds. She was diagnosed with autism spectrum disorder at age 2, after genetic testing ruled out fragile X and Rett syndromes.
This girl also struggled academically and experienced behavioral difficulties, including violent outbursts.
While in the first grade, she began having trouble seeing the classroom’s chalkboard. Initial eye tests reported 20/20 vision, but was amended to 20/200 in the right eye and 20/300 in the left eye, following an electroretinography test at a children’s hospital. The threshold for legal blindness is 20/200.
A retinal specialist found macular dystrophy, a relatively rare condition, in which the region of the eye with the highest concentration of light-sensitive cells deteriorates. The girl was referred to a genetic counselor, who ordered genetic testing.
While awaiting genetic test results, the family discovered the girl’s twin sister, who had shown no vision problems to that point, could not see the words written in a book with yellow writing on a red page, indicating color blindness.
The first sister’s genetic test returned a diagnosis of Batten disease, also called neuronal ceroid lipofuscinosis, or NCL. A genetic test, which also confirmed Batten disease, was ordered for the second sister, on account of the disorder’s inheritance pattern and because of the one episode of color blindness.
The rare disorder’s symptoms vary widely and often involve vision loss. This typically begins as central vision loss and grows to include peripheral vision.
Genetic defects in one of 14 genes — CLN1 through CLN14 — cause Batten, making a genetic test the gold standard for diagnosis. Genetic testing, however, remains expensive, can take months to complete, and not all Batten disease mutations are known. New ones continue to be discovered.
The twins are now 11 years old and attend public school with help from an aide.
Their symptoms include delusions, obsessive-compulsive behavior, mild-to-moderate dementia, difficulty walking, seizures, and extreme difficulty sleeping. Their medical team involves multiple specialists and they are prescribed multiple medications.
Although children with Batten disease typically appear normal at birth, they begin to miss developmental milestones as they grow and often show regression. Symptoms develop as a child ages and do not appear together.
“Diagnosis can be extremely difficult early in the disease,” the report concluded, “but referral should be made to specialists when the clinical picture does not correlate with the history or when multiple diagnoses are given with suspicion that all the signs and symptoms are part of underlying and undiagnosed syndrome.”