Monogenic short stature

Gene: SHOX

I don't know

The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
It is technically not possible to do SHOX off the panel and given that there is a standalone Clinical Indication for SHOX deficiency (R52) on the Test Directory, this demonstrates that SHOX is clinically relevant to short statue.

Created: 20 Jan 2026, 10:04 a.m. | Last Modified: 20 Jan 2026, 10:04 a.m.

Panel Version: 1.29

The rating of this gene has been updated to GREEN following NHS Genomic Medicine Service approval.

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

Panel Version: 2.33

Comment on phenotypes: Previous phenotypes: Dorsolateral bowed, short radii;Bowing and curving of radius;Radioulnar shortening

Created: 26 Mar 2024, 4:11 p.m. | Last Modified: 26 Mar 2024, 4:11 p.m.

Panel Version: 3.53

There is sufficient evidence linking this gene with various disorders including short stature (MIM# 249700, 127300 and 300582). However, the Endocrine Specialist Group previously determined (2019) that the phenotype was not within the scope of this panel and therefore the decision was made to classify it as Red. This was likely due to the age of onset typically being outside the scope of this clinical indication (height ≤−3 SDS at the age of at least 2 years). Some cases have been reported with a mildly reduced birth length (PMID: 14513876; 15356038) and given the progressive decline in height SDS with age, it may be justified to include SHOX on this panel. Although in most cases growth failure became apparent around school age.

Will flag 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, 4:47 p.m. | Last Modified: 5 Jan 2023, 4:47 p.m.

Panel Version: 2.12

Review submitted on behalf of Helen Storr. Mode of inheritance: Haploinsufficiency. Phenotypes: The phenotypic spectrum of SHOX deficiency disorders, caused by haploinsufficiency of the short stature homeobox-containing gene (SHOX), ranges from Leri-Weill dyschondrosteosis (LWD) at the severe end of the spectrum to nonspecific short stature at the mild end of the spectrum. SHOX deficiency test can be completed separately but would be logical to include on this panel as pathogenic SHOX variants have been described as well as insetions/deletions/duplications. Important as confirmed defect confers eligibility for hGh therapy. Publications: Well established - severe defects rare, milder defects more prevalent. Mechansim: SHOX is fundemental for the growth and development of bones / skeleton. Penetrance: Full penetrance.

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

Panel Version: 2.5

I don't know

Following discussion with members of the Endocrine Specialist Group at the Webex call on 23.05.19, it was agreed that this gene was outside the scope of this clinical indication. Therefore demoted gene from Green to Red.

Created: 30 May 2019, 9:49 a.m.