The LMSz method - an automatable scalable approach TO CONSTRUCTING GENE-SPECIFIC growth charts in rare disorders

Karen J. Low, Julia Foreman, Rachel J. Hobson, Hannah Kwuo, Elena Martinez-Cayuelas, Berta Almoguera, Purin Marin-Reina, Stefano G. Caraf, Livia Garavelli, Emily Woods, Meena Balasubramanian, Allan Bayat, Charlotte W. Ockeloen, Caroline M. Wright, Helen V. Firth, and Tim J. Cole

Health professionals measure and plot children’s growth at intervals on appropriate charts to track the trajectory against reference centiles. Many children with genetic disorders plot on an extreme centile—in itself a clue to a possible underlying genetic diagnosis. Once a genetic diagnosis is made, plotting on a standard chart may be misleading. It may, for example, suggest a child is of short stature and underweight when they are growing normally for their genetic disorder, leading to clinical/parental anxiety resulting in unnecessary investigation and unwarranted/ineffective intervention. Conversely, abnormal growth may be incorrectly ascribed to the underlying genetic disorder, and other causes left untreated. Gene-specific growth charts are therefore important in pediatric care. However, due to the small numbers of affected individuals, few gene-specific growth charts are available. This proof-of-principle study tests a new method for constructing growth charts in rare disorders based on small datasets, which we call the LMSz method. We call it this because it applies the LMS method on the z-score scale.