New Study Reveals Rett Syndrome Can Strike Males

A new study has found that the genetic flaw responsible for Rett syndrome can strike males, even where there is not a family history of the rare brain disorder. Report co-author Dr. Helen Leonard, who heads the Australian Rett Syndrome Study at the Telethon Institute for Child Health Research, said the finding means that testing for the genetic disorder should be considered in some baby boys who develop progressive serious neurological problems.

"The common thinking in the past had been that Rett syndrome only affects girls, and that the genetic flaw would be so serious in boys that they would die before birth," Leonard said. "Worldwide there have only been 11 previously established cases in boys who have presented early in life with a severe clinical picture of progressive neurological decline and breathing abnormalities starting soon after birth. All but two had a family history of a girl in the family with Rett syndrome. This study has confirmed a further 4 cases with no family history."

The study, published in the international journal Neurology, was a collaborative effort between researchers from Australia and the United States.

"Genetic testing is used to diagnose Rett syndrome in girls who present with typical symptoms after the age of 1 year," Leonard said. "Prenatal diagnosis is also available in subsequent pregnancies for mothers of girls with Rett syndrome but beyond these families, doctors generally wouldn't test for the problem—especially in baby boys. It is likely that some baby boys with early severe progressive encephalopathy could go undiagnosed and we encourage pediatricians to think about this as a possible cause of severe neurological abnormalities."

Leonard said one of the cases was managed by Princess Margaret Hospital Pediatrician Dr. Jackie Scurlock. The genetic testing for that case was undertaken by Dr. Mark Davis and Professor Nigel Laing at the Neurogenetics Laboratory at Royal Perth Hospital. "While sadly the child had died at 14 months of age, it has been important for the parents to finally have a diagnosis, even after his death," Dr Leonard said.

Rett syndrome is a neurological disorder often misdiagnosed as autism, cerebral palsy or non-specified developmental delay caused by a defective regulatory MECP2 gene found on the X chromosome. The disorder is seen almost exclusively in females. Unlike females, who have two X-chromosomes, males have an X and a Y chromosome. Because males lack a "backup" copy of the X chromosome that can compensate for a defective one, flaws in MECP2 are often lethal to the male fetus. The syndrome occurs in a variety of racial and ethnic groups worldwide and is now known to occur in 1:10,000 to 1:23,000 female births, but incidence may be far greater as new genetic evidence is discovered.

Development appears normal until 6-18 months of age, followed by loss of acquired speech and hand skills, slowing of head growth and development of stereotyped repetitive hand movements such as hand washing, hand wringing, hand tapping, hand clapping and hand mouthing. Stereotyped hand movements may change over time and additional problems may include seizures, breathing irregularities (hyperventilation and apnea), teeth grinding and curvature of the spine (scoliosis).