Clinical Indication ID & Name
Fetal anomalies with a likely genetic cause
Test Group
Core
Specialties
Test code
R21.1
Test name
N/A
Target genes
Genomewide
Test scope
n/a
Test method/ technology
Common aneuploidy testing
Optimal Family Structure
n/a
Eligibility Criteria
For more detailed guidance for R21 outlined in the fetal whole exome service guidance documentation please contact your local Genomic Laboratory Hub.
Fetus with multiple major structural abnormalities detected on fetal ultrasound where multidisciplinary review to include clinical genetics, tertiary fetal medicine specialists, clinical scientists and, where appropriate, relevant paediatric specialists considers a monogenic malformation disorder is likely.
This indication is relevant in ongoing pregnancies where a genetic diagnosis may influence management of the ongoing pregnancy and NOT where there is imminent fetal loss or termination of pregnancy, or miscarriage has already occurred
NOTE: This indication is for use when rapid/urgent testing is required. Please use R412 for non-urgent testing
Clinical examples
• Fetuses with multiple anomalies, suspected skeletal dysplasias (IUGR should be excluded), large echogenic kidneys with a normal bladder, major CNS abnormalities (excluding neural tube defects), multiple contractures (excluding isolated bilateral talipes).
• Nuchal translucency measured between 11 and 14 weeks gestation of greater than 6.5mm plus another anomaly (that can include a minor finding) with a normal array CGH
• Isolated non-immune fetal hydrops (detected at or after the routine 18-20-week scan in the second or third trimesters), defined as fluid/oedema in at least two compartments (e.g. skin, pleural, pericardial or ascites) with a normal array CGH
• Persistent nuchal translucency (>3.5mm) can only be considered in the presence of other structural abnormalities in two or more systems.
• Minor ‘markers of aneuploidy’ – choroid plexus cysts, echogenic foci, mild renal pelvis dilation, small nasal bone, long bones on 3rd centile etc are excluded.
• Mild ventriculomegaly should only be considered as an abnormality if the posterior horn is persistently
>11mm on two or more scans. Under these circumstances it is not considered a major CNS abnormality in isolation
• Abnormality of the corpus callosum, either partial or complete agenesis – either in isolation or with other anomalies
• Pregnancies of consanguineous couples that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely
• Recurrences of particular fetal anomalies in pregnancies of the same couple that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely due to the recurrence. Neural tube defects excluded
Exclusion criteria
• Confirmed aneuploidy or pathogenic copy number variant consistent with fetal anomalies detected by microarray
• Fetuses with confirmed thanatophoric dysplasia, achondroplasia or Apert syndrome on other relevant rapid tests (R23, R24, R25, R306 or R309) are excluded.
• Cases where familial causative variant(s) are known – targeted testing should be performed
• For cases where sonographic findings indicate a specific monogenic disorder, targeted testing should be applied where appropriate
• Where termination of pregnancy has already been decided or when fetal demise has occurred or is imminent then rapid exome sequencing will not be performed. Appropriate testing should be implemented postnatally using the R27 clinical indication (Congenital malformation and dysmorphism syndromes – microarray and sequencing).
Test code
R21.2
Test name
N/A
Target genes
Fetal anomalies (478)
Test scope
n/a
Test method/ technology
WES or Large Panel
Optimal Family Structure
n/a
Eligibility Criteria
For more detailed guidance for R21 outlined in the fetal whole exome service guidance documentation please contact your local Genomic Laboratory Hub.
Fetus with multiple major structural abnormalities detected on fetal ultrasound where multidisciplinary review to include clinical genetics, tertiary fetal medicine specialists, clinical scientists and, where appropriate, relevant paediatric specialists considers a monogenic malformation disorder is likely.
This indication is relevant in ongoing pregnancies where a genetic diagnosis may influence management of the ongoing pregnancy and NOT where there is imminent fetal loss or termination of pregnancy, or miscarriage has already occurred
NOTE: This indication is for use when rapid/urgent testing is required. Please use R412 for non-urgent testing
Clinical examples
• Fetuses with multiple anomalies, suspected skeletal dysplasias (IUGR should be excluded), large echogenic kidneys with a normal bladder, major CNS abnormalities (excluding neural tube defects), multiple contractures (excluding isolated bilateral talipes).
• Nuchal translucency measured between 11 and 14 weeks gestation of greater than 6.5mm plus another anomaly (that can include a minor finding) with a normal array CGH
• Isolated non-immune fetal hydrops (detected at or after the routine 18-20-week scan in the second or third trimesters), defined as fluid/oedema in at least two compartments (e.g. skin, pleural, pericardial or ascites) with a normal array CGH
• Persistent nuchal translucency (>3.5mm) can only be considered in the presence of other structural abnormalities in two or more systems.
• Minor ‘markers of aneuploidy’ – choroid plexus cysts, echogenic foci, mild renal pelvis dilation, small nasal bone, long bones on 3rd centile etc are excluded.
• Mild ventriculomegaly should only be considered as an abnormality if the posterior horn is persistently
>11mm on two or more scans. Under these circumstances it is not considered a major CNS abnormality in isolation
• Abnormality of the corpus callosum, either partial or complete agenesis – either in isolation or with other anomalies
• Pregnancies of consanguineous couples that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely
• Recurrences of particular fetal anomalies in pregnancies of the same couple that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely due to the recurrence. Neural tube defects excluded
Exclusion criteria
• Confirmed aneuploidy or pathogenic copy number variant consistent with fetal anomalies detected by microarray
• Fetuses with confirmed thanatophoric dysplasia, achondroplasia or Apert syndrome on other relevant rapid tests (R23, R24, R25, R306 or R309) are excluded.
• Cases where familial causative variant(s) are known – targeted testing should be performed
• For cases where sonographic findings indicate a specific monogenic disorder, targeted testing should be applied where appropriate
• Where termination of pregnancy has already been decided or when fetal demise has occurred or is imminent then rapid exome sequencing will not be performed. Appropriate testing should be implemented postnatally using the R27 clinical indication (Congenital malformation and dysmorphism syndromes – microarray and sequencing).
Test code
R21.3
Test name
N/A
Target genes
Genomewide
Test scope
n/a
Test method/ technology
Microarray
Optimal Family Structure
n/a
Eligibility Criteria
For more detailed guidance for R21 outlined in the fetal whole exome service guidance documentation please contact your local Genomic Laboratory Hub.
Fetus with multiple major structural abnormalities detected on fetal ultrasound where multidisciplinary review to include clinical genetics, tertiary fetal medicine specialists, clinical scientists and, where appropriate, relevant paediatric specialists considers a monogenic malformation disorder is likely.
This indication is relevant in ongoing pregnancies where a genetic diagnosis may influence management of the ongoing pregnancy and NOT where there is imminent fetal loss or termination of pregnancy, or miscarriage has already occurred
NOTE: This indication is for use when rapid/urgent testing is required. Please use R412 for non-urgent testing
Clinical examples
• Fetuses with multiple anomalies, suspected skeletal dysplasias (IUGR should be excluded), large echogenic kidneys with a normal bladder, major CNS abnormalities (excluding neural tube defects), multiple contractures (excluding isolated bilateral talipes).
• Nuchal translucency measured between 11 and 14 weeks gestation of greater than 6.5mm plus another anomaly (that can include a minor finding) with a normal array CGH
• Isolated non-immune fetal hydrops (detected at or after the routine 18-20-week scan in the second or third trimesters), defined as fluid/oedema in at least two compartments (e.g. skin, pleural, pericardial or ascites) with a normal array CGH
• Persistent nuchal translucency (>3.5mm) can only be considered in the presence of other structural abnormalities in two or more systems.
• Minor ‘markers of aneuploidy’ – choroid plexus cysts, echogenic foci, mild renal pelvis dilation, small nasal bone, long bones on 3rd centile etc are excluded.
• Mild ventriculomegaly should only be considered as an abnormality if the posterior horn is persistently
>11mm on two or more scans. Under these circumstances it is not considered a major CNS abnormality in isolation
• Abnormality of the corpus callosum, either partial or complete agenesis – either in isolation or with other anomalies
• Pregnancies of consanguineous couples that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely
• Recurrences of particular fetal anomalies in pregnancies of the same couple that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely due to the recurrence. Neural tube defects excluded
Exclusion criteria
• Confirmed aneuploidy or pathogenic copy number variant consistent with fetal anomalies detected by microarray
• Fetuses with confirmed thanatophoric dysplasia, achondroplasia or Apert syndrome on other relevant rapid tests (R23, R24, R25, R306 or R309) are excluded.
• Cases where familial causative variant(s) are known – targeted testing should be performed
• For cases where sonographic findings indicate a specific monogenic disorder, targeted testing should be applied where appropriate
• Where termination of pregnancy has already been decided or when fetal demise has occurred or is imminent then rapid exome sequencing will not be performed. Appropriate testing should be implemented postnatally using the R27 clinical indication (Congenital malformation and dysmorphism syndromes – microarray and sequencing).
Test code
R21.4
Test name
N/A
Target genes
Fetal anomalies (478)
Test scope
n/a
Test method/ technology
Exon level CNV detection by MLPA or equivalent
Optimal Family Structure
n/a
Eligibility Criteria
For more detailed guidance for R21 outlined in the fetal whole exome service guidance documentation please contact your local Genomic Laboratory Hub.
Fetus with multiple major structural abnormalities detected on fetal ultrasound where multidisciplinary review to include clinical genetics, tertiary fetal medicine specialists, clinical scientists and, where appropriate, relevant paediatric specialists considers a monogenic malformation disorder is likely.
This indication is relevant in ongoing pregnancies where a genetic diagnosis may influence management of the ongoing pregnancy and NOT where there is imminent fetal loss or termination of pregnancy, or miscarriage has already occurred
NOTE: This indication is for use when rapid/urgent testing is required. Please use R412 for non-urgent testing
Clinical examples
• Fetuses with multiple anomalies, suspected skeletal dysplasias (IUGR should be excluded), large echogenic kidneys with a normal bladder, major CNS abnormalities (excluding neural tube defects), multiple contractures (excluding isolated bilateral talipes).
• Nuchal translucency measured between 11 and 14 weeks gestation of greater than 6.5mm plus another anomaly (that can include a minor finding) with a normal array CGH
• Isolated non-immune fetal hydrops (detected at or after the routine 18-20-week scan in the second or third trimesters), defined as fluid/oedema in at least two compartments (e.g. skin, pleural, pericardial or ascites) with a normal array CGH
• Persistent nuchal translucency (>3.5mm) can only be considered in the presence of other structural abnormalities in two or more systems.
• Minor ‘markers of aneuploidy’ – choroid plexus cysts, echogenic foci, mild renal pelvis dilation, small nasal bone, long bones on 3rd centile etc are excluded.
• Mild ventriculomegaly should only be considered as an abnormality if the posterior horn is persistently
>11mm on two or more scans. Under these circumstances it is not considered a major CNS abnormality in isolation
• Abnormality of the corpus callosum, either partial or complete agenesis – either in isolation or with other anomalies
• Pregnancies of consanguineous couples that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely
• Recurrences of particular fetal anomalies in pregnancies of the same couple that do not strictly fulfil the above criteria, but where a monogenic disorder is considered likely due to the recurrence. Neural tube defects excluded
Exclusion criteria
• Confirmed aneuploidy or pathogenic copy number variant consistent with fetal anomalies detected by microarray
• Fetuses with confirmed thanatophoric dysplasia, achondroplasia or Apert syndrome on other relevant rapid tests (R23, R24, R25, R306 or R309) are excluded.
• Cases where familial causative variant(s) are known – targeted testing should be performed
• For cases where sonographic findings indicate a specific monogenic disorder, targeted testing should be applied where appropriate
• Where termination of pregnancy has already been decided or when fetal demise has occurred or is imminent then rapid exome sequencing will not be performed. Appropriate testing should be implemented postnatally using the R27 clinical indication (Congenital malformation and dysmorphism syndromes – microarray and sequencing).
Commissioning group
Core
Overlapping idications
• R22 Fetus with a likely chromosomal abnormality test (after second trimester loss where there were fetal anomalies and all third trimester losses) should be used instead where findings indicate that a chromosomal cause should be looked for but the additional yield of genomewide sequencing is considered insufficient • R27 Congenital malformation and dysmorphism syndromes should be used for non-urgent testing e.g. where there is imminent fetal loss or termination of pregnancy, or miscarriage has already occurred • Where findings indicate that there is a likely diagnosis R24 Achondroplasia, R25 Thanatophoric dysplasia or of R23 Apert syndrome, those tests should be used instead • R14 Acutely unwell children with a likely monogenic disorder should be used for urgent testing in the postnatal setting
Address for samples/request forms
Genetics Laboratory
5th Floor Tower Wing
Guy’s Hospital
London
SE1 9RT
Contact with queries
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/
Request form download
Consent record
See consent guidance in test request form
Sample requirements
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