Growth failure in early childhood

Gene: NF1

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains AMBER. The additional comments from GLH's is that this is as specialist test

Created: 31 Jan 2023, 5:28 p.m. | Last Modified: 31 Jan 2023, 5:28 p.m.

Panel Version: 2.33

Comment on list classification: Short stature is a variable feature of NF1-related Noonan syndrome but >3 unrelated individuals have been reported with height at least 3 SDS below the mean. Although from the literature it was not clear whether this degree of severity can be reached within the first two years of life. Therefore, flagging for GMS expert review by the Endocrine Specialist Group to reach consensus as to whether this gene is appropriate for inclusion.

Created: 5 Jan 2023, 5:27 p.m. | Last Modified: 5 Jan 2023, 5:27 p.m.

Panel Version: 2.17

Review submitted on behalf of Helen Storr. Mode of inheritance: AD. Phenotypes: 15 RASopathy genes are already included in the panel. These cause a range of clinical features within the Noonan syndrome / overlapping RASopathy spectrum disorders. >80% children with NS have growth failure. It is a multi-system disorder with several other important features that need to be identified/screened for including cardiac disease, cancer susceptibility, developmental problems and learning difficulties. The panel needs to updated to reflect the expanding gene list causing RASopathies. Publications: Although RASopathy genes are included on this panel, this needs to be updated / expanded with more newly identified genes and in line with current guidance (recent review - Zenker et al, Arch Dis Child 2022). Mechansim: Dysregulation of RAS-MAPK pathway with concomitant impact on growth and GH signalling. Penetrance: Variable penetrance depending on the gene - some unclear.

Created: 22 Dec 2022, 11:07 a.m. | Last Modified: 22 Dec 2022, 11:07 a.m.

Panel Version: 2.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown