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).

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).

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).

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).