Medical Mystery: Only 1 Identical Twin Has Rare Illness
A study suggests that genetic differences between twins may explain why a disease afflicts one twin, but not the other.
When the girl was 8 years old, she started to rapidly gain weight, and put on 75 pounds by the time she was 9. She was instructed to exercise, which helped stabilize her weight, but when she exerted herself, she turned blue.
Then at 9, she developed breathing problems. Doctors first thought she had asthma, then pneumonia. It wasn't until she was taken to the emergency room with extremely low oxygen levels in her blood that doctors suspected her seemingly disjoined symptoms might be related.
The girl was later diagnosed with Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation, or ROHHAD, an extremely rare condition that has been identified in just 75 people worldwide.
But there is something that makes this girl's case even more unique: She has an identical twin. Although the pair have the same DNA, the girl's sister has so far shown no signs of the affliction.
That's puzzling because researchers had suspected ROHHAD was genetic.
"[The other] twin continues to do fine, which is amazing," said Dr. Pallavi Patwari, who treated the girl at Children's Memorial Hospital in Chicago, and is one of the world's few experts on ROHHAD. "It really speaks to the fact that there's a lot of things that we need to learn about ROHHAD," Patwari said.
The twins' case, overseen by Patwari and her colleagues, provides a unique window to study ROHHAD's cause. It suggests that epigenetics, or the way our cells read our genes, may play a greater role than genes themselves, she said. Though identical twins have the same DNA sequence, their cells could read their genes differently.
"We really have to start looking more broadly than the simple DNA sequence," Patwari said.
Children with ROHHAD suffer an array of symptoms. The first sign is usually rapid weight gain. Other symptoms include early puberty, breathing problems and tumors in nerve tissue. The disease usually strikes between the ages of 1 and 10.
Many of the disease's features are caused by problems in the part of the brain called the hypothalamus, which is involved in regulating the body's automatic functions, such as body temperature, hunger and breathing.
The breathing problems in ROHHAD are unique, Patwari said. "It's not that they work hard to breathe or that they feel short of breath," she said. It's that the brain does not send signals to increase the breathing rate when it needs to, such as when the oxygen levels are too low.
The twin with ROHHAD later developed tumors in her nerve tissue, which were removed, and problems with her heart rate. She had a pacemaker implanted when she was 10 years old. Now 13, her condition is stable, and she requires ventilator support only at night.
The other twin also gained weight when she was a teen, but her weight gain was mild compared to that of her sister, and she did not have breathing problems.
Is it genetic?
Although only one twin developed ROHHAD, the disease could still be partly genetic, the researchers said. It could be that a mutation predisposes someone to ROHHAD, but something in the environment triggers its development.
Another idea is that the disease is set off by the body's response to cancer cells, although tumors occur in only about 40 percent of cases.
Patwari said she and colleagues hope to compare the entire genomes of the twins to gain insight into ROHHAD's cause. They also want to look for the presence of epigenetic changes that might turn certain genes on or off. However, obtaining funding for this research has been difficult.
Research on this rare disorder might also have broad applications. Patwari hopes it can provide a greater knowledge of what causes obesity.
"If we understand ROHHAD, we're hoping we'll understand a piece of what goes into the actions that cause obesity in general," Patwari said.
Pass it on: A case of twin girls in which one twin has a ROHHAD and the other does not may provide insight into the cause of this rare disorder.
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