Newswise — Growth charts for children with rare genetic disorders – giving healthcare professionals and families clearer guidance on how a child is developing – have been created by an international team, led by the University of Bristol. 

The National Institute for Health and Care Research (NIHR)-funded study is published in the European Journal of Human Genetics (EJHG) today [13 October]. 

The new method, called LMSz, builds on standard population growth charts but adapts them for very small groups of children with rare genetic conditions. 

Growth charts — the familiar lines on a child’s height and weight chart— are an important part of everyday paediatric care. They help healthcare professionals check whether a child is growing as expected and spot health concerns early. 

In the UK, a child’s Personal Child Health Record (PCHR) – commonly known as the “red book” – is a vital health and development record given to parents at birth to track a child’s growth, vaccinations, and key developmental milestones. It’s used by both parents and healthcare professionals to record health information and ensure a child receives timely check-ups, screenings, and immunisations. 

But for children with rare genetic conditions, standard growth charts often don’t tell the full story. These children may grow much more slowly or quickly than other children, leaving parents and healthcare professionals unsure whether the child’s growth is typical for their condition. Until now, there hasn’t been enough data to make accurate, condition-specific growth charts.

An international team of researchers has solved this problem with a new method that can create reliable growth charts even when only a small number of cases are available. 

The study used data from almost 600 children worldwide to make growth charts for six rare genetic conditions: ANKRD11, ARID1B, ASXL3, DDX3X, KMT2A, and SATB2. 

Dr Karen Low, NIHR Clinical Research Fellow in Bristol Medical School: Population Health Sciences (PHS), who led the research, said: “Parents of children with rare genetic conditions often feel anxious when their child’s growth looks very different from other children. They also tell us that health professionals can make them very worried about this or question why their child isn’t growing.” 

“Our growth charts help show what’s typical for that specific condition, which can provide reassurance or might highlight in which children medical intervention is required which supports better medical care.”

The new growth charts show how growth patterns vary between different conditions. For example, some children tend to be much smaller than average, while others may gain weight more rapidly over time. This information can help healthcare professionals make more informed decisions and give families a clearer picture of what to expect as their child grows.

The team’s method was developed with DECIPHER and is now being built into DECIPHER, a widely used online platform for understanding genetic variation hosted at EMBL’s European Bioinformatics Institute (EMBL-EBI). This means growth charts could soon be available for thousands of rare conditions, helping healthcare professionals and families around the world.

Based on the study’s preprint paper, the new method is already being used by two other research groups for other rare disease disorders.

Dr Karen Low added: “We hope our new method will mean that condition specific charts become a standard part of care for children with rare genetic conditions. 

“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.”

Paper

‘The LMSz method – an automatable scalable approach to constructing gene-specific growth charts in rare disorders’ by Karen J. Low et al. in European Journal of Human Genetics (EJHG) [open access]

Case Study: Charlie’s story — a journey to diagnosis

Charlie was diagnosed with KBG syndrome shortly before his second birthday. In the lead-up to his diagnosis, he experienced several small but seemingly unrelated health issues, leading to visits with multiple specialists, including gastroenterologists, paediatricians, neonatologists, and dietitians.

His family was already familiar with genetic disorders as Charlie’s older brother had been diagnosed at birth with Osteogenesis Imperfecta type 4. This connection helped Charlie’s parents seek answers when he continued to face developmental and growth challenges.

At 20 months old, genetic testing finally provided clarity for Charlie with a KGB syndrome diagnosis.

Nicola, Charlie’s mum, explains why participating in the study meant so much to her: “The GenROC study caught my eye when I connected with other families whose children also had KBG syndrome.

“During Charlie’s first year, he struggled to gain weight, and it felt like we were under constant scrutiny from healthcare professionals. There were daily weigh-ins in the early weeks, followed by weekly weigh-ins. I was determined to continue breastfeeding, as I had successfully breastfed Charlie’s older brother, even with his condition. But I felt enormous pressure to supplement with formula, even though I knew that would make feeding more difficult.

“The healthcare teams seemed overly focused on numbers rather than seeing Charlie as an individual. I was sent to hospital with him on one occasion because of his lack of weight gain. He was labelled as having ‘failed to thrive’ — a phrase that made me feel like I was failing as a parent. And that label will remain on his medical records forever.

“But the truth was, Charlie had not failed to thrive at all — he simply did not fit the generic growth charts. I chose to take part in this study to help ensure other families don’t have to go through the same stressful experience we did.”