- Height Standard Deviation Score (SDS) <-3 (very significant short stature – well below the 0.4th centile) AND
- At least one of:
- being born small for gestational (birth weight and/or length <-2SDS), ± a history of intra-uterine growth restriction
- Body disproportion – e.g. discrepancy between stature and head size, limb to spine disproportion, limb asymmetry
- Dysmorphic features e.g. facial dysmorphism,polydactyly/syndactyly, ear abnormalities
- Aberration in the GH-IGF axis (evidence of GH insensitivity or deficiency)
- Other pituitary hormonal deficiencies
- Family history (short stature that is explained or idiopathic in parents, affected siblings,cousins) and/or consanguinity
- Other features such as cleft palate, hearing loss, visual impairment with eye abnormalities including anophthalmia/microphthalmia, optic nerve hypoplasia, retinal dystrophy, forebrain abnormalities and learning difficulties
- For all patients with no abnormalities of the GH-IGF-I axis classified as
Idiopathic Short Stature or who are small for gestational age with failure of catch up growth, a skeletal survey should be performed.
- Acquired causes of short stature, e.g. autoimmune, intracranial neoplasia, infective causes such as Group B Streptococcal meningitis, Langerhans cell Histiocytosis, trauma, previous treatment for malignancy including irradiation, exogenous glucocorticoid use, psychosocial growth failure, chronic disease
- Syndromes associated with short stature such as Turner syndrome, Noonan syndrome, Down syndrome, other chromosomal disorders. However, if the patient has a clinical diagnosis of, e.g. Noonan syndrome, and testing of known genes associated with the syndrome has not identified a pathogenic mutation, then they should be included in the 100000 genomes study.
- Foetal alcohol syndrome
- Genetically proven skeletal dysplasias such as hypochondroplasia or
- Genetically proven Silver-Russell syndrome
Prior genetic testing guidance
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.
PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.
Prior genetic testing genes
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
- All patients with short stature and other features such as
developmental delay and dysmorphism should have a CGH DNA microarray with no pathogenic copy number variants detected
prior to enrolment
- Additional genetic testing should have been performed as
These requirements will be kept under continual review during the main programme and may be subject to change.« Back to Disease List