Vistara non-invasive prenatal screen Hypochondro- Causes a mild form of dwarsm; up to 80% Vistara identies probability for conditions that may have otherwise gone undetected until after birth plasia may cause seizures with secondary or into childhood. All conditions are inherited in an autosomal or X-linked dominant fashion, which means that FGFR3 developmental delay if the mutation is present, the child will be affected by the condition and experience related symptoms. Intellectual Causes intellectual disability and ~100% disability developmental delays SYNGAP1 Condition1 Clinical Cases Ultrasound ndings2,3 Clinical Detection Gene(s) synopsis2,3 caused by actionability rate for Jackson Weiss A type of craniosynostosis; more de novo None Third Non- gene1 syndrome also causes foot abnormalities severe mutations2,3 trimester specic FGFR2 forms Achondroplasia The most common form 80% Labor and delivery >96% FGFR3 of skeletal dysplasia; may management, monitor Juvenile A rare pediatric blood cancer; ve- unknown cause hydrocephalus, for spinal stenosis, early myelomonocytic year survival is approximately 50% delayed motor milestones, sleep studies to reduce leukemia (JMML) and spinal stenosis risk of SIDS PTPN11 Alagille Affects multiple organ systems 50% to 70% Symptom-based >86% LEOPARD Similar to Noonan syndrome, unknown syndrome and may cause growth problems, treatment syndrome 1,2 with notable brown skin spots JAG1 congenital heart defects, and (Noonan (lentigines); causes short stature, vertebral differences syndrome heart defects, bleeding problems, with multiple and, in some cases, mild Antley Bixler A type of craniosynostosis; also more Fetal MRI, avoid >96% lentigines) intellectual disabilities syndrome causes premature fusion of the severe instrumented delivery, PTPN11, RAF1 FGFR2 arm bones, blockage of the nasal forms corrective surgery, monitor passage, and permanently exed for hydrocephalus Muenke A type of craniosynostosis; unknown or extended joints syndrome may cause hearing loss, FGFR3 developmental delays, and cleft Apert A type of craniosynostosis; also more Fetal MRI, avoid >96% lip and/or palate syndrome causes abnormal formation of the severe instrumented delivery, FGFR2 ngers, toes, and vertebrae, and forms corrective surgery, monitor Noonan Causes short stature, heart 25% to 70% other organ anomalies for hydrocephalus syndrome defects, bleeding problems, and, 1,3,4,5,6,8,9 in some cases, mild intellectual Cardiofaciocu- Causes abnormalities of the heart, majority Fetal >96% PTPN11, SOS1, disabilities taneous face, skin, and hair; may cause echocardiogram RAF1, RIT1, KRAS, syndrome 1,3,4 developmental delays and NRAS, SOS2, BRAF, MAP2K1, intellectual disability SHOC2, BRAF, MAP2K2 MAP2K1, HRAS, CBL CATSHL Acronym stands for camptodactyly, unknown Early adoptionof sign >96% syndrome tall stature, scoliosis, and language and behavioral Osteogenesis Causes fragile bones that more FGFR3 hearing loss; may increase risk for intervention imperfecta, break easily, often without severe intellectual disability type I,II,III,IV an identiable cause forms COL1A1, COL1A2 CHARGE Acronym stands for coloboma, majority Early referral to >91% syndrome heart defects, atresia of the endocrinology, adoption Pfeiffer A type of craniosynostosis; also more CHD7 choanae, retardation of growth and of sign language, and syndrome causes hearing loss, intellectual severe development, genital abnormality, behavioral intervention type 1,2,3 disability, hand abnormalities, and forms ear abnormalities; may cause FGFR2 may result in early death hearing loss, developmental delays, and cleft lip and/or palate Cornelia de Lange Causes a range of 99% Monitor for cardiac, 53% to syndrome 1,2,3,4,5 physical, cognitive, and GI, and limb >96% Rett syndrome Causes a rapid regression in >99% NIPBL, SMC1A, medical challenges comorbidities MECP2 language and motor skills at 6 to 18 SMC3, RAD21, months of age; autism, seizures, and HDAC8 long QT syndrome are often present Costello Causes heart defects, intellectual majority Nasogastric or >92% syndrome disability, developmental delays, gastronomy feeding, Sotos syndrome 1 Overgrowth syndrome; also causes >95% HRAS growth delays, and increased risk behavioral and NSD1 developmental delays, intellectual of malignant tumors medical intervention disability, and behavioral problems Crouzon A type of craniosynostosis; also more Fetal MRI, avoid instru- >96% syndrome causes hearing loss and dental severe mented delivery, corrective Thanatophoric A severe skeletal disorder that majority FGFR2, FGFR3 problems in some cases forms surgery, monitor for dysplasia, typically results in stillbirth or hydrocephalus, early types I,II neonatal death due to respiratory adoption of sign language FGFR3 failure Ehlers-Danlos Causes defects in connective 50% Orthotic treatment, >92% Tuberous Causes benign tumor growth 66% syndrome, classic, tissue that can vary from mildly monitoring for vascular sclerosis 1,2 in many organ systems in the body type VIIA, cardiac loose joints to life-threatening complications TSC1, TSC2 that can be life-threatening; may valvular form, complications, such as aortic also cause seizures and secondary type VIIB dissection developmental delays COL1A1, COL1A2 Epileptic Causes seizures with secondary majority Monitor and >84% encephalopathy, developmental delay treat seizures early infantile, 2 CDKL5 = some types or cases Condition1 Clinical Cases Ultrasound ndings2,3 Clinical Detection Gene(s) synopsis2,3 caused by actionability rate for de novo None Third Non- gene1 mutations2,3 trimester specic Hypochondro- Causes a mild form of dwarsm; up to 80% Monitor and >96% plasia may cause seizures with secondary treat seizures FGFR3 developmental delay Intellectual Causes intellectual disability and ~100% Early behavioral >86% disability developmental delays interventions SYNGAP1 Jackson Weiss A type of craniosynostosis; more Fetal MRI, avoid >96% syndrome also causes foot abnormalities severe instrumented delivery, FGFR2 forms corrective surgery, mon- itor for hydrocephalus Achondroplasia The most common form 80% FGFR3 of skeletal dysplasia; may Juvenile A rare pediatric blood cancer; ve- unknown Monitor bloodwork >96% cause hydrocephalus, myelomonocytic year survival is approximately 50% and medical delayed motor milestones, leukemia (JMML) intervention and spinal stenosis PTPN11 Alagille Affects multiple organ systems 50% to 70% LEOPARD Similar to Noonan syndrome, unknown Fetal >96% syndrome and may cause growth problems, syndrome 1,2 with notable brown skin spots echocardiogram JAG1 congenital heart defects, and (Noonan (lentigines); causes short stature, vertebral differences syndrome heart defects, bleeding problems, with multiple and, in some cases, mild Antley Bixler A type of craniosynostosis; also more lentigines) intellectual disabilities syndrome causes premature fusion of the severe PTPN11, RAF1 FGFR2 arm bones, blockage of the nasal forms passage, and permanently exed Muenke A type of craniosynostosis; unknown Fetal MRI, corrective >96% or extended joints syndrome may cause hearing loss, surgery, early adoption of FGFR3 developmental delays, and cleft sign language, and Apert A type of craniosynostosis; also more lip and/or palate behavioral intervention syndrome causes abnormal formation of the severe FGFR2 ngers, toes, and vertebrae, and forms Noonan Causes short stature, heart 25% to 70% Fetal echocardiogram, >92% to other organ anomalies syndrome defects, bleeding problems, and, labor and delivery >96% 1,3,4,5,6,8,9 in some cases, mild intellectual management, early Cardiofaciocu- Causes abnormalities of the heart, majority PTPN11, SOS1, disabilities assessment for learning taneous face, skin, and hair; may cause RAF1, RIT1, KRAS, differences syndrome 1,3,4 developmental delays and NRAS, SOS2, BRAF, MAP2K1, intellectual disability SHOC2, BRAF, MAP2K2 MAP2K1, HRAS, CBL CATSHL Acronym stands for camptodactyly, unknown syndrome tall stature, scoliosis, and Osteogenesis Causes fragile bones that more Labor and delivery >92% FGFR3 hearing loss; may increase risk for imperfecta, break easily, often without severe management, neonatal intellectual disability type I,II,III,IV an identiable cause forms care, early recognition COL1A1, COL1A2 and treatment of fractures CHARGE Acronym stands for coloboma, majority syndrome heart defects, atresia of the Pfeiffer A type of craniosynostosis; also more Fetal MRI, avoid >96% CHD7 choanae, retardation of growth and syndrome causes hearing loss, intellectual severe instrumented delivery, development, genital abnormality, type 1,2,3 disability, hand abnormalities, and forms corrective surgery, ear abnormalities; may cause FGFR2 may result in early death monitor for hydrocepha- hearing loss, developmental delays, lus, early adoption of sign and cleft lip and/or palate language, and behavioral intervention Cornelia de Lange Causes a range of 99% syndrome 1,2,3,4,5 physical, cognitive, and Rett syndrome Causes a rapid regression in >99% Evaluate for cardiac >78% NIPBL, SMC1A, medical challenges MECP2 language and motor skills at 6 to 18 risk, monitor and treat SMC3, RAD21, months of age; autism, seizures, and seizures, early medical HDAC8 long QT syndrome are often present and behavioral interventions Costello Causes heart defects, intellectual majority syndrome disability, developmental delays, Sotos syndrome 1 Overgrowth syndrome; also causes >95% Fetal echocardiogram, >47% HRAS growth delays, and increased risk NSD1 developmental delays, intellectual