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The National Genomic Test Directories specify which genomic tests are commissioned by the NHS in England, to be delivered by Genomic Laboratory Hubs.

Clinical Indication ID & Name

R453

Monogenic short stature

Test Group

Endocrinology

Test code

R453.1

Test name

N/A

Target genes

Growth failure in early childhood (473)

Test scope

n/a

Test method/ technology

WES or Medium Panel

Optimal Family Structure

n/a

Eligibility Criteria

Height/length more than 3 standard deviations below the mean at the age of at least 2 years in the absence of microcephaly, OR
Clinical features strongly indicative of a diagnosis of Silver-Russell syndrome, as assessed by the presence of 3 or more of the features below*:
1. SGA (birth weight and/or birth length): ≤−2 SDS for gestational age
2. Postnatal growth failure: Height at 24 ± 1 months ≤−2 SDS or height ≤−2 SDS below mid-parental target height
3. Relative macrocephaly at birth: Head circumference at birth ≥1.5 SDS above birth weight and/or length SDS
4. Protruding forehead: Forehead projecting beyond the facial plane on a side view as a toddler (1–3 years)
5. Body asymmetry: Leg length discrepancy of ≥0.5 cm or arm asymmetry or leg length discrepancy <0.5 cm with at least two other asymmetrical body parts (one non-face) 6. Feeding difficulties and/or low BMI: BMI ≤−2 SDS at 24 months or current use of a feeding tube or cyproheptadine for appetite stimulation *See Wakeling et al 2017, PMID: 27585961

Test code

Test name

N/A

Target genes

11p15 imprinted growth regulatory region and UPD7 growth regulatory critical region

Test scope

n/a

Test method/ technology

Methylation testing

Optimal Family Structure

n/a

Eligibility Criteria

Height/length more than 3 standard deviations below the mean at the age of at least 2 years in the absence of microcephaly, OR
Clinical features strongly indicative of a diagnosis of Silver-Russell syndrome, as assessed by the presence of 3 or more of the features below*:
1. SGA (birth weight and/or birth length): ≤−2 SDS for gestational age
2. Postnatal growth failure: Height at 24 ± 1 months ≤−2 SDS or height ≤−2 SDS below mid-parental target height
3. Relative macrocephaly at birth: Head circumference at birth ≥1.5 SDS above birth weight and/or length SDS
4. Protruding forehead: Forehead projecting beyond the facial plane on a side view as a toddler (1–3 years)
5. Body asymmetry: Leg length discrepancy of ≥0.5 cm or arm asymmetry or leg length discrepancy <0.5 cm with at least two other asymmetrical body parts (one non-face) 6. Feeding difficulties and/or low BMI: BMI ≤−2 SDS at 24 months or current use of a feeding tube or cyproheptadine for appetite stimulation *See Wakeling et al 2017, PMID: 27585961

Test code

Test name

N/A

Target genes

Genomewide

Test scope

n/a

Test method/ technology

Exon level CNV detection by MLPA or equivalent

Optimal Family Structure

n/a

Eligibility Criteria

Height/length more than 3 standard deviations below the mean at the age of at least 2 years in the absence of microcephaly, OR
Clinical features strongly indicative of a diagnosis of Silver-Russell syndrome, as assessed by the presence of 3 or more of the features below*:
1. SGA (birth weight and/or birth length): ≤−2 SDS for gestational age
2. Postnatal growth failure: Height at 24 ± 1 months ≤−2 SDS or height ≤−2 SDS below mid-parental target height
3. Relative macrocephaly at birth: Head circumference at birth ≥1.5 SDS above birth weight and/or length SDS
4. Protruding forehead: Forehead projecting beyond the facial plane on a side view as a toddler (1–3 years)
5. Body asymmetry: Leg length discrepancy of ≥0.5 cm or arm asymmetry or leg length discrepancy <0.5 cm with at least two other asymmetrical body parts (one non-face) 6. Feeding difficulties and/or low BMI: BMI ≤−2 SDS at 24 months or current use of a feeding tube or cyproheptadine for appetite stimulation *See Wakeling et al 2017, PMID: 27585961

Test code

Test name

N/A

Target genes

Growth failure in early childhood (473)

Test scope

n/a

Test method/ technology

n/a

Optimal Family Structure

n/a

Eligibility Criteria

Height/length more than 3 standard deviations below the mean at the age of at least 2 years in the absence of microcephaly, OR
Clinical features strongly indicative of a diagnosis of Silver-Russell syndrome, as assessed by the presence of 3 or more of the features below*:
1. SGA (birth weight and/or birth length): ≤−2 SDS for gestational age
2. Postnatal growth failure: Height at 24 ± 1 months ≤−2 SDS or height ≤−2 SDS below mid-parental target height
3. Relative macrocephaly at birth: Head circumference at birth ≥1.5 SDS above birth weight and/or length SDS
4. Protruding forehead: Forehead projecting beyond the facial plane on a side view as a toddler (1–3 years)
5. Body asymmetry: Leg length discrepancy of ≥0.5 cm or arm asymmetry or leg length discrepancy <0.5 cm with at least two other asymmetrical body parts (one non-face) 6. Feeding difficulties and/or low BMI: BMI ≤−2 SDS at 24 months or current use of a feeding tube or cyproheptadine for appetite stimulation *See Wakeling et al 2017, PMID: 27585961

Commissioning group

Specialised

Overlapping idications

- R452 Silver Russell Syndrome and Temple Syndrome - R88 Severe microcephaly – if the presentation includes severe microcephaly - R27 Paediatric disorders – if the presentation appears syndromic - R52 Short stature – SHOX deficiency - please order this test if you suspect SHOX deficiency as SHOX is not included on the panel test for short stature due to technical limitations. - R104 Skeletal dysplasia – if there is disproportion or a skeletal survey suggestive of primary bone pathology (outside of the SHOX remit) - R26 Likely common aneuploidy for suspected Turner Syndrome

Address for samples/request forms

Genetics Laboratory
5th Floor Tower Wing
Guy’s Hospital
London
SE1 9RT

Contact with queries

gst-tr.southeastglh@nhs.net

Supporting documents

n/a

Education resources

n/a

Turn around times

All our turnaround times are listed on our specific turn around page https://southeastgenomics.nhs.uk/professionals/service-turn-around-times/

Consent record

See consent guidance in test request form

Sample requirements

Sample Requirements Each sample must be sent labelled with 3 patient identifiers and must state the sample type clearly on the sample container. Sample Rejection Samples may be rejected for the following reasons: 1. Samples and request form do not show at least three identical patient identifiers 2. The sample is in the incorrect collection media 3. The request form is not sufficiently completed 4. The sample is not of sufficient volume 5. The sample is too old Sample Storage and Volume Required: Perirpheral blood in an EDTA tube: Adult and children 4 ml, Infants (0-2 years) 1 ml or a DNA sample (3-5µg of purified DNA). Where it is not possible to collect peripheral blood we will accept a saliva sample (please contact the lab for specific details). Storage, sample packing and transportation: Blood should be stored at 4°C where possible. Send at room temperature by first class post or by courier. Patient/Clinician Instructions: N/A Factors affecting performance of test/interpretation of results: Clotted samples are unsuitable for DNA analysis. Blood Samples in incorrect anticoagulant tubes may be rejected.