Prenatal Genetics

• Cardio-Facio-Cutaneous Syndrome
• Costello Syndrome
• Noonan Syndrome

• Prenatal ultrasound findings suggestive of Noonan syndrome, including cystic hygroma
• Fetus with ultrasound anomalies & parent with clinical diagnosis of Noonan syndrome

• Next-Gen Sequencing

• Acro-Renal-Ocular syndrome
• Cornelia de Lange Syndrome
• Duane-Radial Ray syndrome
• Ectodermal Dysplasia
• Ectrodactyly
• Ectrodactyly- Ectodermal Dysplasia- Clefting (EEC) syndrome
• Holt-Oram syndrome
• Limb-Mammary Syndrome
• Prenatal Cornelia de Lange Syndrome (CdLS)
• Townes-Brocks Syndrome

• Prenatal diagnosis in a fetus based on ultrasound findings suggestive of a limb abnormality syndrome
• Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
• Distinguish between causes and forms of limb abnormality syndromes
• Genetic counseling, especially regarding recurrence risk

• Deletion/Duplication Analysis
• Next-Gen Sequencing

• Achondrogenesis
• Achondroplasia (ACH)
• Bruck syndrome
• Campomelic Dysplasia (CD)
• Chondrodysplasia Punctata (CDPX1)
• Fibrochondrogenesis
• Frontometaphyseal dysplasia
• Greenberg skeletal dysplasia
• Hypochondroplasia (HCH)
• Osteogenesis Imperfecta (OI)
• Pseudoachondroplasia (PSACH)
• Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (SADDAN)
• Short-Rib Thoracic Dysplasia (SRTD)
• Spondylocostal dysostosis
• Thanatophoric Dysplasia (TD)

• Prenatal diagnosis in a fetus based on ultrasound findings suggestive of a skeletal dysplasia
• Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies
• Distinguish between causes and forms of skeletal dysplasias
• Genetic counseling, especially regarding recurrence risk

• Next-Gen Sequencing
• Deletion/Duplication Analysis

• Campomelic Dysplasia (CD)

• Full sequencing and deletion/duplication testing for fetuses with ultrasound findings suggestive of CD
• Mutation-specific testing for fetuses with a family history of a known SOX9 mutation

• Deletion/Duplication Analysis
• Next-Gen Sequencing

• Prenatal Cornelia de Lange Syndrome (CdLS)

• Prenatal diagnosis in a fetus based on ultrasound findings suggestive of a Cornelia de Lange syndrome
• Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies

• Capillary Sequencing
• Deletion/Duplication Analysis

• 655.23 Hereditary disease in family possibly affecting fetus
• 655.83 Other known or suspected fetal abnormality, not elsewhere classified

• Acro-Renal-Ocular syndrome
• Duane-Radial Ray syndrome

• Full sequencing testing for fetuses with prenatal ultrasound findings suggestive of Duane-Radial Ray Syndrome / Acro-Renal-Ocular Syndrome
• Mutation-specific testing for fetuses with a family history of a known SALL4 mutation

• Capillary Sequencing

• Ectrodactyly
• Ectrodactyly- Ectodermal Dysplasia- Clefting (EEC) syndrome
• Hay-Wells Syndrome
• Split Hand - Split Foot Malformation

• Hotspot analysis for fetuses with prenatal ultrasound findings suggestive of EEC or related syndromes.
• Mutation-specific testing for fetuses with a family history of a known TP73L (TP63) mutation

• Capillary Sequencing

• Holt-Oram syndrome

• Full gene sequencing testing for fetuses with prenatal ultrasound findings suggestive of Holt-Oram Syndrome.
• Mutation-spcific testing for fetuses with a family history of a known TBX5 mutation

• Capillary Sequencing

• Townes-Brocks Syndrome

• Prenatal diagnosis based on fetal ultrasound abnormalities
• Mutation-specific testing for fetuses with a family history of a known SALL1 mutation

• Capillary Sequencing

• COACH Syndrome
• Joubert Syndrome
• Meckel-Gruber Syndrome
• Oral-Facial Digital Type 6

• Prenatal imaging findings suggestive of JSRD including molar tooth sign, other structural brain malformations, encephalopcele, renal disease, polydactyl, and cleft/lip palate

• Next-Gen Sequencing
• Deletion/Duplication Analysis

• Alpha-Dystroglycanopathies
• Lissencephaly
• Walker–Warburg Syndrome

• Prenatal imaging findings suggestive of lissencephaly

• Next-Gen Sequencing
• Deletion/Duplication Analysis

• Cerebellar Hypoplasia
• Pontocerebellar Hypoplasia (PCH)

• Prenatal imaging findings suggestive of pontocerebellar hypoplasia

• Next-Gen Sequencing
• Deletion/Duplication Analysis

• Holoprosencephaly

• Full gene sequencing testing for fetuses with prenatal ultrasound findings suggestive of holoprosencephaly
• Mutation-specific testing for fetuses with a family history of a known mutation in the SHH, ZIC2, SIX3, or TGIF gene

• MLPA
• Next-Gen Sequencing

• CRASH Syndrome
• Hydrocephalus, X-linked
• MASA Syndrome

• Full sequencing for fetuses with prenatal ultrasound findings suggestive of X-linked hydrocephalus/L1CAMrelated disorder
• Mutation-specific testing for fetuses with a family history of a known L1CAM mutation

• Capillary Sequencing
• Exon Array Dx

• 655.23 Hereditary disease in family possibly affecting fetus
• 655.83 Other known or suspected fetal abnormality, not elsewhere classified

• CRASH Syndrome
• Hydrocephalus, X-linked
• MASA Syndrome

• Full sequencing for fetuses with prenatal ultrasound findings suggestive of X-linked hydrocephalus/L1CAMrelated disorder.
• Mutation-specific testing for fetuses with a family history of a known L1CAM mutation

• Capillary Sequencing

• 655.23 Hereditary disease in family possibly affecting fetus
• 655.83 Other known or suspected fetal abnormality, not elsewhere classified

• Spinal Muscular Atrophy

• ​Molecular confirmation of a clinical diagnosis
• Identification of at-risk family members
• Assist with treatment/ management decisions
• Recurrence risk assessment

• MLPA
• Capillary Sequencing

• Fragile X Syndrome
• Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)
• Premature Ovarian Failure (FMR1-Associated)

• Testing for fetuses at increased risk for Fragile X syndrome based on family history

• PCR Fragment Analysis

• Ambiguous external genitalia
• Discordant external genitalia

• Genital ambiguity or discordant external genitalia

This panel includes 19 genes; some variants in these genes may manifest
with genital ambiguity or external genitalia that are discordant with gender based on genetic
testing findings. Pathogenic variants in these genes may be suspected when the fetal karyotype
is 46,XY or non-invasive prenatal screening is consistent with the presence of a Y chromosome
but ultrasound reveals apparently female or ambiguous external genitalia. Ultrasound detection
of abnormalities of the genitalia can be detected as early as the 2nd trimester of pregnancy.
Depending on the underlying disorder, renal malformations, congenital heart defects,
limb/skeletal malformations, intrauterine growth restriction, cleft lip/cleft palate, and
congenital brain defects may also be observed by ultrasound. Note that some ultrasound
findings may not be detectable until the 3rd trimester of pregnancy. In addition, some disorders
may also present with abnormal findings on second trimester maternal serum screening, such as
abnormal maternal serum estriol (MS-uE3) levels.

• Next-Gen Sequencing
• Deletion/Duplication Analysis

• 5-Alpha Reductase Deficiency

• Full gene sequencing for fetuses with prenatal ultrasound findings suggestive of 46,XY disorder of sex development
• Mutation-specific testing for fetuses with a family history of known SRD5A2 mutations

• Capillary Sequencing

• Androgen Insensitivity Syndrome (AIS)
• Testicular Feminization Syndrome (TFM)

• Full gene sequencing testing for fetuses with prenatal ultrasound findings suggestive of AIS.
• Prenatal diagnosis when karyotype is 46,XY and ultrasound shows female genitalia
• Prenatal diagnosis in at-risk pregnancies

• Capillary Sequencing

• Antley-Bixler Syndrome (ABS)
• Cytochrome P450 Oxidoreductase (POR) Deficiency

• Full gene sequencing for fetuses with prenatal ultrasound findings suggestive of Antley-Bixler syndrome or cytochrome P450 Oxidoreductase (POR) deficiency
• Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies

• Capillary Sequencing

• Gender Verification

• Ambiguous Gender

• 46,XY Gonadal Dysgenesis (SRY-related)

• Full gene sequencing testing for fetuses with prenatal ultrasound findings suggestive of 46,XY gonadal dysgenesis
• Mutation-specific testing for fetuses with a family history of a known SRY mutation

• Capillary Sequencing

• 46,XY Gonadal Dysgenesis With or Without Adrenal Insufficiency (NR5A1-related)

• Full gene sequencing for fetuses with prenatal ultrasound findings suggestive of 46,XY disorder of sex development
• Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies

• Capillary Sequencing

• Adrenal Hypoplasia Congenita (AHC), X-linked

• Full gene sequencing for male fetuses with a history of low maternal uE3, particularly in the presence of a family history suggestive of X-linked AHC
• Mutation-specific testing for fetuses with a family history of known NR0B1 mutations

• Capillary Sequencing

• CHARGE Syndrome

• Full gene sequencing for fetuses with prenatal ultrasound findings suggestive of CHARGE syndrome
• Mutation-specific testing for fetuses with a family history of a known CHD7 mutation

• Capillary Sequencing

• Smith-Lemli-Opitz Syndrome

• Full gene sequencing for fetuses with increased 7-DHC levels measured in amniotic fluid or CVS tissue.
• In the case of ultrasound findings and/or abnormal maternal serum screening suggestive of SLOS and no family history, prenatal measurement of 7-DHC levels is recommended as a first step.
• Mutation-specific testing for fetuses with a family history of two known DHR7 mutations.

• Capillary Sequencing

• Tuberous Sclerosis Complex (TSC)

• Full gene sequencing and exon-level deletion/duplication for fetuses with prenatal ultrasound findings suggestive of TSC.
• Variant-specific testing for fetuses with a family history of a known TSC1 or TSC2 pathogenic variant.

• Deletion/Duplication Analysis
• Next-Gen Sequencing

• Mutation-specific testing for fetuses with a family history of a known mutation

• Anophthalmia
• Microphthalmia

• Full sequencing testing for fetuses with prenatal ultrasound findings suggestive of anophthalmia/microphthalmia

• Deletion/Duplication Analysis
• Next-Gen Sequencing

• 655.2 Hereditary disease in family possibly affecting fetus [0,1,3]
• 655.8 Other known or suspected fetal abnormality, not elsewhere classified [0,1,3] Suspected damage to fetus from: environmental toxins intrauterine contraceptive device

• Establishing a molecular diagnosis in a fetus with abnormal ultrasound findings

With a turnaround time (TAT) of 3-4 weeks, the fetal specimen and specimens from both biological parents must be submitted at the same time, along with clinical information, in order to begin testing. This test requires approval by GeneDx before ordering; please e-mail WESPrenatal@genedx.com to discuss cases prior to submitting samples.

The XomeDxPrenatal Comprehensive fetal report will also include medically relevant pathogenic or likely pathogenic variants in genes expected to be related to the reported fetal phenotype. Variants of uncertain significance may be reported if there is compelling evidence to suggest clinical significance. In addition, variants of uncertain significance in novel candidate genes may be reported.

• Next-Gen Sequencing

• Establishing a molecular diagnosis in a fetus with abnormal ultrasound findings.

With a turnaround time (TAT) of 3-4 weeks, the fetal specimen and specimens from both biological parents must be submitted at the same time, along with clinical information, in order to begin testing. This test requires approval by GeneDx before ordering; please e-mail WESPrenatal@genedx.com to discuss cases prior to submitting samples.

The XomeDxPrenatal Targeted fetal report will include medically relevant pathogenic or likely pathogenic variants in genes expected to be related to the reported fetal phenotype. Variants of uncertain significance may be reported if there is compelling evidence to suggest clinical significance.

• Next-Gen Sequencing