
Daniel Sokoloff and his mom, Lara Sokoloff, photographed here when Daniel was younger, were one of 100 families who contributed to a study aimed at understanding common birth defects of the brain.
In the largest genetic study of the most common birth defects of the brain diagnosed during pregnancy, researchers from Seattle Children’s Research Institute say their findings evolve our understanding of brain development. The findings will also change the information given to expecting parents when cerebellar malformations, such as Dandy-Walker malformation and cerebellar hypoplasia, are detected prenatally.
With funding support from the Dandy-Walker Alliance and the Philly Baer Foundation, the results gathered from 100 families provide the most accurate information to date about the genetic and non-genetic causes of birth defects involving the cerebellum. They will also help doctors counsel parents about their child’s prognosis after they’re born and their risk of having another child with the abnormality.
“For those who are pregnant, you certainly don’t want to have a problem with the baby, but if doctors detect a brain abnormality, you want accurate information about what that means,” said Dr. William Dobyns, the senior author on the paper published in the American Journal of Human Genetics and an investigator in the Center for Integrative Brain Research. “It’s the same after birth. If you have a child at risk for developmental challenges, it helps to know the cause and what’s going to happen. This study significantly advances our ability to answer those questions.”
Bringing greater clarity to cerebellar malformations

Drs. William Dobyns (left) and Kim Aldinger (right) study the genetic causes of birth defects of the cerebellum.
Housing 80% of all neurons, the cerebellum is known to control motor coordination as well as integration of sensory input and regulation of attention, mood and emotions. Yet, little is known about the development of the cerebellum and the rise of abnormalities, which can lead to epilepsy, intellectual disability, cerebral palsy and autism in children.
By analyzing the genetic sequencing results, imaging and clinical features of the patients with Dandy-Walker malformation or cerebellar hypoplasia enrolled in the study, Dobyns and lead author, Dr. Kimberly Aldinger, identified 27 different genes as key contributors. Most of the genes identified were already known to cause specific neurodevelopmental syndromes.
In addition to establishing a genetic diagnosis for 36 of the children, their cohort confirmed that many abnormalities, about 30%, were due to prenatal risk factors and would not be expected to have a genetic cause.
“We’ve finally pieced together how to determine whether a birth defect of the brain is genetic or not in any given child,” Dobyns said. “Clear patterns emerged from our detailed study, and we could confidently attribute a full third of cerebellar malformations to non-genetic, prenatal causes. Those with a genetic cause most often arose as a feature that could appear as part of a larger disorder like epilepsy or autism.”
New insight on Dandy-Walker malformation
In children with Dandy-Walker malformation, the most common structural defect of the cerebellum affecting about 1 in every 10,000 births and often a cause of significant intellectual and motor delays, the study showed these abnormalities rarely have a genetic cause. The researchers also looked at long-term outcomes and found that half of the children with a Dandy-Walker malformation went on to have a normal intellectual development, meaning they often participate in typical school classes, go to college and hold jobs as adults.
According to Aldinger, this is more definitive information than what doctors can currently give parents about what to expect in a child with Dandy-Walker.
“When you first see a Dandy-Walker malformation on a prenatal imaging scan, it looks like the brain is severely affected,” she said. “The picture says this looks really bad, and it’s easy for parents to associate this with a significant intellectual disability for the child, but as we saw in our study that’s not the case for a lot of children.”
The start of a diagnostic journey
Dobyns and Aldinger anticipate that the breadth of their findings will change how cerebellar malformations are diagnosed clinically. Historically, Dandy-Walker malformations and cerebellar malformations have served as a primary diagnosis for families.
Based on their findings, a cerebellar malformation detected early in development should prompt a comprehensive clinical evaluation that includes a prenatal history, postnatal neuroimaging and when necessary, genetic testing, to uncover the genetic and non-genetic causes. In most cases, this will provide a more complete picture of the child’s condition and occasionally, it may help doctors identify potential treatments.
“A cerebellar malformation is really the start of a diagnostic journey,” Dobyns said. “For a small number of children, this information will lead us to a silver bullet, an existing therapy that targets the child’s genetic mutation that could present a new treatment pathway. For the majority, children with genetic conditions that we can’t fix, the more we understand, the better we can help the family manage their child’s condition.”
Family contributes to research advance

Daniel (far right) with his family.
Lara Sokoloff and her son, Daniel, participated as one of the families in the study. From his previous position in Chicago, Dobyns first diagnosed Daniel with a cerebellar malformation as an infant when the family was then living in Virginia. Daniel had a subtype known as cerebellar vermis hypoplasia that caused him to have significant developmental delays and some behavioral issues. At 13, he attends special needs classes at school and will need daily care for the rest of his life.
“It’s always helpful when you are a parent of a kid with disabilities to have a team, to know that you have people on your side,” Sokoloff said. “For a long time after Daniel was diagnosed, Dr. Dobyns was the one who was always there to answer my questions.”
Separately, both Dobyns and the Sokoloffs made their way to Seattle and reunited in the Genetics program at Seattle Children’s in 2013. Here, Daniel was one of the 36 children who received a genetic diagnosis after his and his parents’ genes were sequenced as part of the study. It provided information that Sokoloff had been seeking since Daniel was a baby.
“More than anything I wanted to know what was going on with Daniel and why,” she said. “We got the answer we needed and while it didn’t change anything for Daniel, we participated in the study because I’ve always wanted to help people in the future.”
Upon hearing the news of Daniel’s contribution to this research advance, Sokoloff expressed the hope she has for her son and future discoveries.
“The amazing thing about Daniel is he doesn’t go backwards. He doesn’t lose the skills he has gained like walking or communicating verbally,” she said. “He kind of writes his own playbook and because there wasn’t a lot of concrete information available about his diagnosis, I’ve never put a lot of stock in what the outcome might be. This research offers a good step forward for families. There’s just so much we can learn, so who knows what might be possible with more research.”
I would like more information on enrolling my son who is 27 with Dandy-Walker Malformation in the genetic study.
Thank you for reaching out. To learn more about current research studies, please contact our Center for Integrative Brain Research at 206-884-4102.
I was diagnosed with Dandy Walker Syndrome at age 60. I would like to know more on your research.
Thank you for reaching out. To learn more about this research, please contact our Center for Integrative Brain Research at 206-884-4102.
After suffering 2 migraines at the age of 60, I went to the family doc who ordered an mri or cat scan, don’t remember which. Those were the first and only migraines I’ve ever had. The results showed nothing that woul,cause the migraines, but the radiologist said the scan “suggested” Dandy Walker. I’m 72 now and have not given it much thought over the last 12 years. Is there something I should do or just go on with my life? Other than low grade prostate cancer, kidney disease, glaucoma, arthritis, degenerative disc disease (neck area), I’m healthy and active.
Thank you for reaching out, John. I’d encourage you to reach out to the Dandy-Walker Alliance to see if they can connect you with someone for more information. You can reach them on email at comments@dandy-walker.org.
I was diagnosed with Dandy Walker malformation/ Variant at age 60, from MRI. I would like to participate in genetic testing or a clinical study. I have had balance issues, mild learning issues/ disabilities, but have had a full life.
Thank you for reaching out, Ann. I’d encourage you to reach out to the Dandy-Walker Alliance to inquire about any research studies for adults. You can reach them on email at comments@dandy-walker.org.
Hello. My 10 yr old has DW and I am interested in the study. Please contact me. Thank you
Thank you for reaching out. Please email brainresearch@seattlechildrens.org for more information about this study.
My 1 year old has dandy walker but was wondering if this research is just from America ?
Thank you for reaching out. Several international sites participated in this study. You can view a full list of contributors on the paper here. You can also email dandywalker@seattlechildrens.org if you have any additional questions for the researchers.
Hi my daughter is 30 years old and we live in the uk and no one has heard of DWS. Is there anyone in the uk that is involved with your site??
Tina and daughter Nikki
Thank you for reaching out. Researchers from Newcastle University and University College London Institute of Child Health also contributed to this study. You can view a full list of contributors on the paper here. You can also email brainresearch@seattlechildrens.org if you have any additional questions for the researchers.
Hi, my son is 1 year old, he has DWS, we would like to join for the genetic study, we are from Ecuador, and here is not common the syndrome, please your help
Thank you for reaching out, Nadia. Please email brainresearch@seattlechildrens.org for more information about current research studies.
Lindsay, I’m trying to find out where the estimate of Dandy Walker incidence (1/10k) came from in the press release here. This was not in the published article (from what I can tell) and is much higher incidence than many websites/sources (for example, Genetics Home Reference uses 1/10k – 1/30k — a large range, also not referenced). Has there been a new study or estimate that puts the incidence at 1/10k instead of 1/30k? Thank you.
Thank you for reaching out, Deb. I’ve passed your question along to our researchers who provided that figure to me. I’ll let you know if they can point us to a specific source.
The researchers pointed me to a paper published this year from a European cohort, which reports 8.85/100k. Given this recent data, we used the 1/10k estimate from the NIH.
I am a 62 year old woman , with Dandy Walker Malformation/ Variant. I had encephalocele repair as an infant. Ar3 you interested in my story? I have an atypical outcome. Well educated and relatively mild symptoms from this diagnosis.
Thank you for reaching out, Ann. I have passed your information and question along to our research team. They will be in touch directly if they are interested in learning more.