Tag: spina bifida

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A Tiny Chromosomal Deletion is Linked to Spina Bifida

On By ModernMedia
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A group of researchers at the University of California San Diego School of Medicine led an investigation that offers new insight into the causes of spina bifida, the most common structural disorder of the human nervous system.

The group’s work reveals the first link between spina bifida and a common chromosomal microdeletion in humans. The study demonstrates that individuals carrying this chromosomal deletion – present in one of 2500 live births – demonstrate a risk of spina bifida more than 10 times greater than the general public.

The study, published in Science, also underscores the potential role of folic acid (aka vitamin B-9) in reducing the risk of spina bifida.

Professor Joseph G. Gleeson at Rady Children’s Institute for Genomic Medicine, is the senior author of the study. He explained that spina bifida, also known as meningomyelocele, affects one in every 3000 newborns. Unfortunately, the causes are mostly unknown. A few mutations were reported but could only explain a tiny fraction of risk, Gleeson added.

To uncover the genetic causes of the disease, Gleeson’s UC lab joined with colleagues around the world to establish the Spina Bifida Sequencing Consortium in 2015. The consortium began focusing on a tiny deletion in chromosome 22. Chromosome microdeletions refer to a condition in which several genes in a chromosome are missing. The group’s target condition, known as 22q11.2del, has been implicated in a number of other disorders. They began looking for 22q11.2del in spinal bifida patients.

“All patients we recruited have the most severe form of spina bifida, and all underwent best-practice comprehensive genomic sequencing,” Gleeson said. “We identified 22q11.2del in 6 out of 715 patients. This may not seem a high percentage, but this is by far the most common single genetic variation that could contribute to spina bifida.”

He went on to say the group identified eight additional spina bifida patients who carried the deletion from a cohort of approximately 1500 individuals recruited because of the presence of the common 22q11.2 deletion, Gleeson said.

The researchers then narrowed the cause among the many genes in the 22q11.2 deletion to a single gene known as CRKL. Gleeson explained that there are nine other genes in this chromosomal region that could have been the cause. He said the team began a process of elimination, “knocking out” each of the mouse genes one-by-one, when they received a fortuitous email from Dolores Lamb from Weil Cornell College of Medicine. Lamb had noted some of the mice in their vivarium that were missing Crkl and showed spina bifida. (Study co-first author Keng Ioi Vong, PhD, explained that researchers use all capital letters to describe the gene in humans, and lower-case for mice.) Lamb’s group heard about the Gleeson lab project through the Spina Bifida Association.

“This finding really got us excited because it meant that CRKL disruption might be sufficient for spina bifida,” said Vong. “We removed the mouse Crkl gene ourselves and confirmed that some of the mice developed neural tube defects, including spina bifida.” Most of the other genes in 22q11.2 deletion were subsequently excluded, he added.

They next turned their attention to how folic acid may modulate CRKL-mediated spina bifida. Vong noted that prior studies in humans demonstrated that folic acid supplementation prior to conception reduces the incidence of spina bifida and other neural tube defects by up to 30-50 %, but the mechanisms are still a mystery.

“When we deprived the Crkl mutant female mice of folic acid in their chow, many more of their offspring had neural tube defects, and the severity increased dramatically,” Vong explained. “This suggests that folic acid taken by pregnant women may not only reduce the risk, but also the severity of neural tube defects in their offspring.”

“We hope our findings can help the research community to better understand causes of neural tube defects, especially the causes attributable to common genetic findings like 22q11.2 deletion,” Gleeson said. “We also hope our findings can contribute to healthy pregnancies, improved women’s health, and improved outcomes for children.”

Source: University of California – San Diego

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‘Absolutely Amazing’ Results of Baby’s Surgery in the Womb

On By ModernMedia
Baby's hand holding on to an adult's finger. Image by RitaE from Pixabay

When her mother learned of her condition while still pregnant with her, baby Mila became one of dozens of babies with spina bifida who have been treated in the womb with a revolutionary procedure, according to the Great Ormond Street Hospital (GOSH) for Children in London.

Spina bifida is a congenital malformation which occurs in the 4th week post-fertilisation where the embryonic neural tube fails to close, leaving the spinal column split (bifid) and open, exposing the spinal cord. Below the level of the damage on exposed spinal cord, there can be motor and sensory neurological deficit. Orthopaedic abnormalities such as clubfoot are possible. Additionally, the higher up the damage is on the spine, the higher the mortality rate. 

Helena, a mother from the UK who had become pregnant after six IVF attempts, at 20 weeks discovered her baby had spina bifida. A scan showed a huge open lesion on her baby’s lumbar sacral region, exposing her spinal cord. But Helena was aware of pioneering open foetal surgery carried out by the NHS following a diagnosis with a previous pregnancy, and was determined to apply for it.

“I knew if I didn’t get the operation the quality of her life would be very different,” Helena told BBC News.

“It was a very large lesion on her back and half of her spine was exposed. They said that it was likely she will be paralysed, incontinent and will need a shunt to drain the fluid from her brain later on.”

A US study, as reported previously on QuickNews, showed that the benefits of foetal repair surgery continued into later childhood, with those having had foetal repair being six times more likely to go to the toilet unaided than those who had surgery after birth, and were 70% more likely to walk unaided, and twice as likely to walk without braces. They were also more likely to use self-care skills such as brushing teeth and using a fork.  

“The procedure is complex, time-sensitive and not without its risks, but the significant and life-changing impact on babies … and their families, cannot be overstated,” explained Dr Dominic Thompson, lead neurosurgeon at GOSH. “This makes all the difference to the quality of their lives.”

Twenty-five clinicians from GOSH and University College London Hospitals, as well as University Hospitals Leuven in Belgium, were involved in Helena’s surgery, according to BBC News.

The procedure generally involves administering an anaesthetic to the mother, which passes to the foetus through the placenta, and then cutting through the abdomen and uterus to reach the foetus’s spine. Neurosurgeons then take off any skin attached to the exposed spinal cord and place the cord inside the spinal canal before stitching the tissues closed.

In her 23rd week of pregnancy, she received surgery at a specialist hospital in Belgium, and three months later, she gave birth to her daughter Mila at University College London Hospital. According to GOSH, some excess fluid still remains on the newborn’s brain, but Mila is showing signs of healthy development.

“She can move her legs, and she’s got feeling to her toes so it’s absolutely amazing,” Helena told BBC News. “I’m just so grateful to the surgeons who’ve done this operation because her life would look very different without it.” Including Mila, the team has performed the same operation on 32 babies since January 2020.

“We’re very excited about the next phase of the prenatal surgery for babies with spina bifida, including less invasive approaches,” Dr. Paolo De Coppi, part of the fetal surgical team for spina bifida, said in the statement.

“As with any new approach, we first need to fully understand the benefits and risks involved to mother and baby,” De Coppi noted. “While we look to make these future procedures as safe as possible, what is clear is that prenatal surgery for patients with spina bifida leads to better outcomes.”

Source: Live Science

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Foetal Repair of Spina Bifida Improves Outcomes in Children

On By ModernMedia

A follow-up study found further evidence that foetal surgery for spina bifida extends benefits even further into childhood.

Adding to a growing body of research affirming the benefits of fetal surgery for spina bifida, new findings show prenatal repair of the spinal column confers physical gains that extend into childhood.

Spina bifida is a birth defect where the vertebral column is open (bifid), often involving the spinal cord. Myelomeningocele (MMC; open spina bifida) is the clinically most significant, where the spinal neural tube fails to close during development of the embryo. The exposed neural tissue degenerates in utero, causing a neurological deficit that varies with the amount of lesion. This occurs in 1 in 1000 births worldwide.

“This study shows that the benefits of fetal surgery for spina bifida extend beyond early childhood and well into a child’s first decade of life,” said co-author of the study N Scott Adzick, MD, Surgeon-in-Chief at Children’s Hospital of Philadelphia (CHOP), Director of CHOP’s Center for Fetal Diagnosis and Treatment. “This is especially important because of previously raised concerns that the advantages from fetal surgery may decrease over time. Contrary to those concerns, there appears to be a long-term benefit from neural protection in utero.”

The present study is a follow-on of the Management of Myelomeningocele Study (MOMS), which was co-led by investigators at CHOP, Vanderbilt University Medical Center, and the University of California, San Francisco, along with the data coordinating centre at the George Washington University Biostatistics Center. MOMS compared the outcomes of prenatal and traditional postnatal repair of myelomeningocele at 12 and 30 months, showing that there are considerable benefits from prenatal repair. Babies with spina bifida who received foetal surgery were less likely to need a shunt for the buildup of spinal fluid in the brain. Two and a half years after surgery, they walked better and had better overall motor function.

In MOMS2, the children from MOMS were comprehensively examined at ages from five to ten. They were assessed on a range of indicators, including fine motor skills and ability to do tasks unaided. The researchers found continuing benefits, including the foetal repair group being six times more likely to go to the toilet unaided than the postnatal repair group, and were 70% more likely to walk unaided, and twice as likely to walk without braces. They also had greater likelihood of engaging in self-care skills such as brushing teeth and using a fork.

“These data are important for demonstrating that fetal surgery for spina bifida improves mobility well into school age, but the implications of these results are even more profound,” said first author Amy J Houtrow, MD, PhD, MPH, Pediatric Rehabilitation Medicine Division Chief at UPMC Children’s Hospital of Pittsburgh. She said that when children are able to move around by themselves, it has significant positive impacts on their quality of life.

“When we began performing fetal surgery more than two decades ago, we did so with the hope that the procedure would improve lives for children and their families,” explained Dr Adzick. “As we continue to improve the technique, shortening surgery times and increasing the gestational age at birth, we are heartened by these results, which show the lasting benefits of fetal surgery.”

Source: Medical Xpress