“Stop feeding him milk right away – just to be safe” was not what a new mother wanted to hear. The call came several days after Tamara Caspary gave birth to fraternal twins, a boy and a girl. She and husband David Katz were in the period of wonder and panic, both recovering and figuring out how to care for them.
“A nurse called to ask how my son was doing,” says Caspary, a developmental Read more
A genetic disorder caused by silencing of a gene on the X chromosome, fragile X syndrome affects about one child in 5,000, and is more common and more severe in boys. It often causes mild to moderate intellectual disabilities as well as behavioral and learning challenges.
Amy Talboy, MD
The gene responsible for fragile X syndrome, the most common inherited form of intellectual disability, was identified more than 25 years ago. Emory genetics chair Stephen Warren played a major role in achieving that milestone. His work led to insights into the molecular details of learning and memory, and nationwide clinical trials — which have a more complicated story.
Treating the molecular basis of a neurodevelopmental disorder, instead of simply addressing symptoms, is a lofty goal – one that remains unfulfilled. Now a new study, supported by the National Institute of Neurological Disorders and Stroke, is reviving a pharmacological strategy that Warren had a hand in developing.
“This is a very well thought out approach to studying changes in language and learning in children who are difficult to test,” says Amy Talboy, medical director of Emory’s Down Syndrome and Fragile X clinics, who is an investigator in the NINDS study. “It could change how we conduct these types of studies in the future.” Read more
A PNAS paper published MondayÂ demonstrates the kinds of insights that can be gleaned from a large scale sequencing project examining the fragile X gene.
Most children (boys, usually) who have fragile X syndrome have a particular mutation. An expanded â€œtriplet repeatâ€ stretch of DNA, which is outside the protein-coding region of the gene, puts the entire gene to sleep.
At Emory,Â geneticist Steve Warren, cell biologist Gary Bassell and colleagues have been identifying less common changesÂ in the fragile X gene by looking in boys who are developmentally delayed, but donâ€™t have the triplet repeat expansion. The first author of the paper is former postdoc Joshua Suhl, now at Booz Allen Hamilton in Massachusetts.
The authors describe two half-brothers who have the same genetic variant, which changes how production of the FMRP protein is regulated.Â These examples show that the fragile X gene is so central to how neurons function that several kinds of geneticÂ glitches in it can make this finely tuned machine break down.
â€œThis is a hot area and not much is known about it,â€ Warren says. Read more
A studyÂ published in Pediatrics this week tracks “adaptive behavior” asÂ children and adolescents with fragile X syndrome are growing up. This isÂ the largest longitudinal study to date in fragile X, which isÂ the leading inherited cause of intellectual disability and the leading single-gene risk factor for autism spectrum disorder.
Adaptive behavior covers a range of everyday social and practical skills, including communication, socialization, and completing tasks of daily living such as getting dressed. In this study, socialization emerged as a relative strength in boys with fragile X, in that it did not decline as much as the other two domains of adaptive behavior measured: communication and daily living skills.
The “socialization as relative strength in fragile X” findings meshes with a growing awareness in the autism field, summarized nicely here by Jessica Wright at the Simons Foundation Autism Research Initiative, thatÂ fragile X syndrome symptoms are often distinct from those in autism spectrum disorder.
One key distinction between the disorders, for example, is in social interactions. Children with autism and those with fragile X syndrome both shy away from social contact, have trouble making friends and avert their gaze when people look at them.
But children with fragile X syndrome often sneak a peek when the other person turns his back, researchers say. Children with autism, in contrast, seem mostly uninterested in social interactions.
â€œChildren with fragile X syndrome all have very severe social anxiety that plays a big role in the perception that they have autism,â€ saysÂ Stephen Warren, professor of human genetics at Emory University School of Medicine in Atlanta. â€œThey are actually interested in their environment; they are just very shy and anxious about it.â€
In a paper recently published in Journal of Neuroscience, a team led by cell biologist Gary Bassell shows that PI3 kinase inhibitors could restore normal appearance and levels of protein production at the synapses of hippocampal neurons from fragile X model mice. The next steps, studies in animals, are underway.
â€œThis is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism,â€ he says.