# Paper: 'LMSz' - Growth chart reference creation technique for rare conditions

**Category:** [Growth Charts](https://forum.rcpch.tech/c/rcpch-digital-growth-charts/6)
**Created:** 2025-02-06 13:25 UTC
**Views:** 27
**Replies:** 0
**URL:** https://forum.rcpch.tech/t/paper-lmsz-growth-chart-reference-creation-technique-for-rare-conditions/287

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## Post #1 by @pacharanero

Just posting this as it is helpful background information about the difficulties of growth charts for rare conditions.

Long-time friend of the RCPCH and part of the dGC standard-setting team Tim Cole has published some work on creating growth charts data references where there are so few affected individuals that it would be impossible to create a traditional growth chart reference. 

Standard growth chart references usually require very large sample sizes of children (thousands), this is of course impossible where only a few hundred affected patients exist worldwide, as with some rare genetic disorders.

Where we have existing specialist condition growth charts, as in for Turner and Down syndromes, these are generally where those conditions are actually moderately common in the population.

Tim and collaborators have created a method for making a hybrid of existing large-sample growth references with correcting data from the affected small sample with the genetic condition.

https://www.medrxiv.org/content/10.1101/2024.08.19.24312213v1

## Abstract

**Introduction** Children with monogenic neurodevelopmental disorders often grow abnormally. Gene-specific growth charts would be useful but require large samples to construct them using the conventional LMS method.

**Methods** We transformed anthropometry to British 1990 reference z-scores for 328 UK and 264 international probands with *ANKRD11, ARID1B, ASXL3, DDX3X, KMT2A* or *SATB2-*related disorders, and modelled mean and standard deviation (SD) of the z-scores as gene-specific linear age trends adjusted for sex. Back-transforming the mean ±2 SD lines provided gene-specific median, 2nd and 98th centiles.

**Results** The resulting z-score charts look plausible on several counts. Only *KMT2A* shows a (rising) age trend in median height, while BMI and weight increase in several genes, possibly reflecting population trends. Apart from *SATB2* and *DDX3X,* the gene-specific medians are all below the reference (range 0.1th centile for height *KMT2A* to 36th centile for BMI *ANKRD11*). Median OFC shows no age trend, with medians ranging from 10th-30th centile, and *ASXL3* lowest, on the 3rd centile. There are no sex differences in 19/24 cases.

**Conclusions** Our LMSz method produces gene-specific growth charts for rare diseases, an essential clinical tool for paediatric care. We plan to automate it within the DECIPHER platform, enabling availability for all relevant genes.

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**Canonical:** https://forum.rcpch.tech/t/paper-lmsz-growth-chart-reference-creation-technique-for-rare-conditions/287
**Original content:** https://forum.rcpch.tech/t/paper-lmsz-growth-chart-reference-creation-technique-for-rare-conditions/287