Rare Case of Early Puberty Reported in 8-year-old With Rett Syndrome
A rare case of premature puberty was reported in an 8-year-old girl diagnosed with Rett syndrome years earlier.
Reports of precocious puberty — occurring before 8 years of age — are scarce in Rett patients. It typically begins at an average age of 12.2, studies have noted.
Researchers in Chengdu, China, described an 8-year old girl who was referred to their hospital with signs of puberty, including early breast and pubic hair development, that had begun six months earlier. Examination revealed an abnormal early-onset puberty, with ovaries already developed and advanced bone age (estimated for a girl 9.5 years old).
Her development was normal for her first year of life, raising her head by the time she was 2 months old, rolling over at 4 months, and sitting without aid at around 6 months. She could say papa and mama at 12 months old.
By age 18 months, she had the first episode of loss of consciousness and convulsions. She was diagnosed with epilepsy after showing abnormalities on electroencephalogram, a test that measures electrical activity in the brain.
Daily convulsions continued at this age, and she was never able to stand on her own and lost the ability to speak.
She also moved her hands with no discernible point or purpose and her head size was smaller than what is expected for her age. A brain MRI scan showed abnormalities in the white matter — which contains the projections that neurons in different regions of the brain use to communicate with each other — and brain shrinkage.
A genetic analysis then identified a mutation (called c.1157_1197del) in MECP2 — the main disease-causing gene of Rett syndrome — which resulted in an abnormal MECP2 protein. This protein regulates other genes’ activities and is involved in the function and communication of nerve cells.
Researchers found no such mutation in her parents, meaning it had occurred spontaneously in the child.
The girl was diagnosed with Rett syndrome at age 4, with signs of mental retardation as well as seizures.
She received treatment with the anticonvulsants topiramate and Keppra (levetiracetam). Her seizure frequency dropped to once to twice over six months, and she remained stable for about two years. At age 7, shortly before puberty’s onset became evident, frequent seizures returned.
Biochemical tests found high levels of the luteinizing hormone that helps to control the menstrual cycle, the follicle-stimulating hormone that stimulates the growth of ovarian follicles, and estradiol, an active form of estrogen. Her level of free thyroxine was low, due to an underactive thyroid gland.
An ultrasound showed numerous follicles in the girl’s ovaries, indicative of the onset of puberty.
Her precocious puberty was successfully treated with a monthly therapy that mimics the action of the gonadotropin releasing hormone — called leuprorelin — and daily with Euthyrox, used to treat thyroid hormone deficiency.
One year later her seizures were under control, occurring once or twice a year.
This study reports “an additional case of Rett syndrome with precocious puberty, and we revealed a de novo [spontaneous] disease-causing variant in MECP2,” the researchers wrote.
“The association of precocious puberty and MECP2 mutations has not been reported before, and further experiments are needed for the clarification of this,” they added.