A novel statistical method is poised to revolutionize the care of children with rare genetic disorders by providing, for the first time, reliable growth charts tailored to their specific conditions. An international team of researchers, led by the University of Bristol, has developed a technique that overcomes the challenge of limited patient data, a common hurdle in the study of rare diseases. This new approach, called LMSz, adapts standard population growth charts for very small groups, offering families and healthcare professionals a clearer picture of a child’s development. The study, funded by the National Institute for Health and Care Research (NIHR), was published in the European Journal of Human Genetics.
For parents of children with rare genetic conditions, the standard growth charts used in pediatric care can be a source of anxiety and uncertainty. These children often grow at a much different pace—either faster or slower—than their peers, making it difficult for doctors to assess whether their development is on a healthy track for their specific disorder. The lack of sufficient data has historically prevented the creation of accurate, condition-specific growth charts. The new LMSz method addresses this gap by using data from nearly 600 children worldwide to generate growth charts for six rare genetic conditions: ANKRD11, ARID1B, ASXL3, DDX3X, KMT2A, and SATB2. These charts can help in providing reassurance to parents and may also highlight when medical intervention is necessary.
A New Approach to Growth Charting
The LMSz method represents a significant advancement in pediatric care for rare diseases. It builds upon the standard growth charts that are a familiar part of childhood health, often recorded in the “red book,” or Personal Child Health Record, in the United Kingdom. These charts are crucial for monitoring a child’s growth, tracking vaccinations, and ensuring developmental milestones are met. However, their utility is limited when it comes to children with rare genetic syndromes whose growth patterns deviate significantly from the norm.
The Challenge of Small Datasets
The primary obstacle to creating growth charts for rare diseases is the scarcity of data. With only a small number of diagnosed individuals for any given condition, traditional statistical methods are often inadequate. The international research team tackled this problem by developing a method that can produce reliable charts even with a limited number of cases. This innovative approach has the potential to be applied to a wide range of rare conditions, offering a new level of personalized care. The development of the LMSz method was a collaborative effort, with input from DECIPHER, a widely used online platform for understanding genetic variation.
The Six Conditions Studied
The initial application of the LMSz method focused on six specific rare genetic disorders, each with its own unique impact on a child’s growth and development. The study included children with mutations in the ANKRD11, ARID1B, ASXL3, DDX3X, KMT2A, and SATB2 genes. By analyzing data from a global cohort of nearly 600 children, the researchers were able to create the first-ever reliable growth charts for these conditions.
Varied Growth Patterns
The new charts reveal distinct growth patterns among the different conditions. Some children, for instance, tend to be significantly smaller than average, while others may experience more rapid weight gain over time. This detailed information is invaluable for both clinicians and families. It allows for more informed decision-making regarding a child’s health and provides a clearer understanding of what to expect as the child grows. The ability to distinguish between typical growth for a specific condition and a potential health concern is a critical step forward in managing these complex disorders.
Impact on Families and Healthcare
The creation of these new growth charts has a profound impact on the families of children with rare genetic disorders. Dr. Karen Low, a NIHR Clinical Research Fellow at the Bristol Medical School and the lead researcher on the study, highlighted the emotional toll that standard growth charts can take on parents. “Parents of children with rare genetic conditions often feel anxious when their child’s growth looks very different from other children,” she said. “They also tell us that health professionals can make them very worried about this or question why their child isn’t growing.”
The condition-specific charts can alleviate this anxiety by providing a more accurate benchmark for a child’s growth. This can offer reassurance to families and help them to better understand their child’s unique developmental journey. Furthermore, these charts empower healthcare professionals to provide better medical care by enabling them to more accurately identify when a child’s growth deviates from the expected pattern for their condition, which may signal the need for medical intervention.
Future of Personalized Pediatric Care
The successful development of the LMSz method and its application to six rare genetic disorders is just the beginning. The research team’s method is now being integrated into DECIPHER, which is hosted at the European Bioinformatics Institute of the European Molecular Biology Laboratory (EMBL-EBI). This integration will make it possible to generate growth charts for thousands of other rare conditions, significantly expanding the reach and impact of this research.
Wider Adoption and Collaboration
The potential for this new method is already being recognized by the broader scientific community. Even before the study’s official publication, two other research groups had begun using the LMSz method for other rare disease disorders, based on the preprint paper. This early adoption is a testament to the urgent need for such tools in the field of pediatric genetics. The researchers hope that their work will lead to condition-specific growth charts becoming a standard part of care for all children with rare genetic conditions.
As Dr. Low stated, “Our study is about giving healthcare professionals and families the tools they need to understand and support a child’s unique growth journey. Every child deserves care that’s based on the best possible information.” The development of the LMSz method is a significant step toward achieving that goal, promising a future where personalized care is more accessible for some of the most vulnerable patients.