First in-person CRD family conference

The CTCF-Related Disorder community of families held their first in-person conference this weekend at Emory. What started five years ago with a Facebook group, established by a mom who wanted to share information about her son’s genetic diagnosis, became concrete in a way that it wasn’t before.

Children with distinctive facial features of CTCF-related disorder were running or bouncing a ball in the lobby of the Whitehead building. Parents could trade tips on caring for their kids. Researchers gathered samples and outlined ambitious plans.

CRD families assembled at lunchtime. Several of the children played in the 3rd floor seminar room during the conference.

Genetics counseling student Jenna Mathwig discussed a “deep phenotyping” project that will recruit dozens of families to catalog the array of symptoms and features experienced by people with CTCF-Related Disorder. The project will build upon the 2023 paper from Hong Li and colleagues describing CRD’s phenotypic spectrum. Reports of individuals with CTCF-related disorders have been published starting in 2013, and now more than 100 are known worldwide.

Jenna Mathwig explains deep phenotyping

On Sunday, families from 11 US states and one from Norway attended. One thing was clear: these families have plenty of information to contribute. Many parents said they had to push for genetic sequencing after their children experienced developmental delays, and they continue to encounter obstacles when seeking autism diagnosis or other support.

“The families often know more than I do, which is fantastic,” Mathwig said.

Families stayed at the Emory Conference Center hotel, with their travel paid through a supplement to the main National Institutes of Health CTCF-related disorder grant. The CRD Center thanks the Gabbard family for their generous support of the conference.

Some questions from parents exposed the limits of current knowledge, such as concerns about screening for Wilms tumor, a common pediatric kidney tumor that has been reported in several individuals with CRD. Other emerging features – not present in all individuals with CRD -- include osteoporosis, variations in pain sensitivity, liver dysfunction, hypoglycemia or recurrent infections.

For clinical guidance, families heard from DOHG’s Amy Talboy, along with gastroenterologist Sharmistha Rudra and sleep specialist Amit Shah, both from Children’s Healthcare of Atlanta.

Panelists fielded questions from parents

Riding the neural crest

CRD arises from mutations in the gene encoding CTCF, a DNA-binding protein with 11 zinc fingers that organizes loops of chromatin into functionally distinct units. Although CRD is usually thought of as a neurodevelopmental disorder, it affects the whole body, sometimes leading to craniofacial alterations or gastrointestinal issues, for example.

Victor Corces, who has been studying CTCF’s function for years, said he is still revising his ideas about how mutations in the gene can perturb development. At the conference, he said he thought the variety of features could be explained by effects on two cell types, both coming from ectoderm: cells in the central nervous system and neural crest cells, which form bone, cartilage, teeth and smooth muscle as well as neurons and glia. However, families have reported issues outside this framework, such as Wilms tumor or problems with liver function or biliary ducts (kidney arises from mesoderm; liver from endoderm).

Mouse embryo with neural crest cells in GREEN (Sox10)

Kyle Christy, an adult born with CTCF-related disorder, and his parents came to the conference from Arizona, just a few weeks after learning about it and contacting Dr Li. At age 27, after being diagnosed with conditions such as fragile X syndrome and Marfan syndrome, Kyle finally obtained exome sequencing at Mayo Clinic in 2019. The video Mayo made about Kyle and his family doesn’t even mention CTCF, perhaps because less was known about the disorder at the time.