Table 2.
Phenotype and sequencing results from cases with a negative ES result
| Prenatal FBAa | Multisystemic Anomalies | Deep Phenotype | Category of FBA |
|---|---|---|---|
| Cerebellar hypoplasia (HP:0001321) Intracranial cysts (HP:0010576) Abnormal calvarium (HP:0002683) Non-visualization of cavum septum pellucidum (HP:4000138) |
Growth restriction, echogenic kidneys (polycystic), echogenic bowel, hypotelorism | Midline defect Posterior fossa |
|
| Schizencephaly (HP:0010636) | Arthrogryposis | Prior affected pregnancy | Cortical disorder |
| Dandy Walker malformation (HP:0001305) Absent corpus callosum (HP:0001274) Cerebellar and vermian hypoplasia (HP:0001321, HP:0001320) |
Small to absent left orbit | MRI | Midline defect Posterior fossa |
| Vermis abnormality of the cerebellum (HP:0002334) Dandy Walker variant (HP:0001305) |
Truncus arteriosis with VSD | Posterior fossa | |
| Hypoplastic cerebellum (HP:0001321) | Cleft lip/palate; unilateral absent radius | Posterior fossa | |
| Bilateral ventriculomegaly (HP:0002119) Agenesis of corpus callosum (HP:0001274) |
Hypertelorism; omphalocele; likely VSD | CSF disorder Midline defect |
|
| Severe hydrocephalus vs hydranencephaly (HP:0000238 vs HP:0002324) | Amniotic bands arising from umbilical cord, acute angulation of lumbar spine without an ONTD, bilateral facial clefts (lips, palate, nose), fused eyes, left ear small and low set, absent left arm, giant omphalocele with liver, stomach and bowel, bilateral clubbed feet with rocker-bottom appearance, syndacytyly of toes on left foot | CSF disorder | |
| Bilateral ventriculomegaly (HP:0002119) Cerebellar hypoplasia (HP:0001321) Abnormal cavum septum pellucidum (HP:4000138) |
Bilateral hydronephrosis; arthrogryposis with clubbed hands and feet; polyhydramnios | CSF disorder Midline defect Posterior fossa |
|
| Anencephaly (HP:0002323) Previous pregnancy with anencephaly. |
Previous pregnancy with hand webbing | Autopsy Prior affected pregnancy |
Neural tube defect |
| Anencephaly (HP:0002323) | Diaphragmatic hernia, lower lip cleft | Neural tube defect | |
| Enlarged cavum septum pellucidum (N/Ab) Abnormal posterior fossa (HP:0000932) |
Diaphragmatic hernia; shortened long bones; Y shaped gluteal cleft; abnormal facial appearance (hypotelorism, flattened nasal bridge) | Autopsy | Midline defect Posterior fossa |
| Holoprosencephaly (HP:0001360) | Absent nose, absent or hypoplastic orbits (possible single orbit) | Midline defect | |
| Abnormal posterior fossa (HP:0000932) Absent corpus callosum (HP:0001274) Large cystic structure (N/A) |
Pseudocleft of upper lip with prenasal edema; AVSD; borderline platyspondyly; upper extremities: bilateral polydactyly and syndactyly, short radius and ulna; lower extremities: short femurs, short tibias, absent fibulae, polydactyly, clubbed feet. | Midline defect Posterior fossa |
|
| Hypoplastic cerebellum (HP:0001321) Absent cavum septum pellucidum (HP:4000138) Ventriculomegaly (HP:0002119) Two affected pregnancies. |
IUGR, micrognathia, heart defect, arthrogryposis. | Prior affected pregnancy | CSF disorder Midline defect Posterior fossa |
| Ventriculomegaly (HP:0002119) Absent cavum septum pellucidum (HP:4000138) Absent corpus callosum (HP:0001274) |
IUGR, renal agenesis, cleft lip/palate, esophageal pouch, heart defect, arthrogryposis. Two affected pregnancies. | Prior affected pregnancy | CSF disorder Midline defect |
| Severe hydrocephalus with no normal brain anatomy seen (HP:0000238) | Macrosomia: Dating was based on an early first trimester ultrasound. At 20 wk 3 d - measured 23 wk 6. Head, abdomen, femurs, all large (+4 weeks) At 25 wk - measured 31 wk 1 d (+6 weeks) At 31 wk 1 d - measured 37 wk 2 d (+6 weeks) Frontal bone (head) scalloping; Heart defect - hypoplastic left heart. Right sided heart; Bilateral hydronephrosis/hydroureter; Bilateral clubbed feet. |
MRI | CSF disorder |
| Open neural tube defect (HP:0034237) | Scoliosis/kyphosis; Coarctation of the aorta; Absent left arm with small left hand (no humerus, forearm, no bones in small hand), Rocker bottom feet | Neural tube defect | |
| Hydrocephalus (HP:0000238) | First trimester cystic hygroma; Bilateral radial ray malformation with single forearm bone on the right. Absent stomach (possible esophageal atresia); Abnormal cardiac axis, “flat” AV valve, VSD, possible double outlet right ventricle; Right renal agenesis/cystic kidney; Intrabdominal cyst with echogenic rim and associated peritoneal calcifications concerning for early bowel perforation. |
CSF disorder | |
| Small cerebellum (HP:0001321) Smooth brain (HP:0001339) Calcifications (HP:0002514) Arachnoid cyst (HP:0100702) |
IUGR, frontal bossing, Hydroureter, hydronephorosis, long bones short, clubbed feet, left hand fixed, hyperextended, clinodactyly | Posterior fossa Cortical disorder |
|
| Encephalocele (HP:0002084) | Heart defect, omphalocele, cleft lip/palate, right humerus, radius, ulna are missing with 3 digits arising from the scapula, polyhydramnios | Neural tube defect | |
| Microcephaly (HP:0000252) Lissencephaly (HP:0001339) One prior affected pregnancy. |
IUGR, heart defect, pancytopenia, sloping forehead, inverted nipples, Pancreatic atrophy | Autopsy MRI and autopsy on first affected (lived 16 months) Prior affected pregnancy |
Cortical disorder |
| Severe hydrocephalus (HP:0000238) | Cleft lip/palate, horseshoe kidney, polyhydramnios, sacral dimple, VSD | MRI | CSF disorder |
| Enlarged cisterna magna (HP:0011427) Absent corpus callosum (HP:0001274) |
VSD, thickened myocardium, IUGR, ambiguous genitalia. IUFD. | Midline defect Posterior fossa |
|
| Alobar holoprosencephaly (HP:0006988) | Midface hypoplasia, cyclopia. Heart defect - single ventricle. Dilated bowel, enlarged bladder. Cystic mass in umbilical cord. Ambiguious genitalia |
Midline defect | |
| Aprosencephaly (HP:0007268) Microcephaly (HP:0000252) |
Hypoplastic adrenal glands, hypotelorism, hypoplastic palpebral fissures, absent orbits, proboscis, small mouth, anal atresia, heart defect, hypoplastic right lung with single lobe | Autopsy | Midline defect |
| Hydrocephalus (HP:0000238) Thin cortex (N/A) Dangling choriods (N/A) Hypoplastic cerebellum (HP:0001321) |
Right sided aortic arch, VSD, thoracic kyphosis, clubbed feet | CSF disorder Posterior fossa |
|
| Exencephaly (HP:0030769) Large open neural tube defect, similar to rachichisis (HP:0034237) |
Kyphosis - could not see diaphragm, lungs or stomach. Micrognathia | Neural tube defect | |
| Large right posterior encephalocele (HP:0002084) | Large facial midline cleft, clenched hands, 2 VC. Patient reports one hand had no digits, the other had nubs only without bones. Syndactyly of toes. Cloudy corneas. | Neural tube defect | |
| Bilateral ventriculomegaly (HP:0002119) Small cerebellum (HP:0001321) |
Clubbed feet, contracted arms, Abnormal facial profile, NOS. Consanguinity | CSF disorder Posterior fossa |
|
| Encephalocele (HP:0002084) | Cleft lip and palate, anophthalmia, absent external nasal structures with wide spaced nares, anotia, contractures of arms and hands, oligodactyly and syndactyly of hands and feet. | Autopsy | Neural tube defect |
| Lobar holoprosencephaly (HP:0006870) | Thick NT, short arms and legs - fixed position, absent tibia and fibia bilaterally, absent left kidney, transposition of the great arteries, cleft lip palate | Midline defect | |
| Unilateral severe ventriculomegaly vs porencephalic cyst (HP:0002119 vs HP:0002132) | Unilateral clubbed foot, possible heart defect (suboptiomal images) | CSF disorder | |
| Cloverleaf skull (HP:0002676) Dandy Walker malformation (HP:0001305) | IUGR <1%ile, hypoplastic kidneys with oligohydramnios, left sided diaphragmatic hernia, kyphosis. Suboptimal heart due to CDH. | Autopsy | Posterior fossa |
| Absent vs severely hypoplastic cerebellum (HP:0007360 vs HP:0001321) | SUA, anhydramnios, cystic hygroma, echogenic bowel, growth restriction, IUFD 20 weeks. | Posterior fossa | |
| Agenesis corpus callosum (HP:0001274) Arachnoid cyst (HP:0100702) Vermian agenesis (HP:0006817) |
Micropthalmia of the right eye, abnl positioning of left fingers, short femurs and humeri, multiple hemivertebrae | Midline defect Posterior fossa |
|
| Dandy Walker malformation (HP:0001305) Hydrocephalus (HP:0000238) Dysplastic cerebellum and vermis (HP:0006893) Dysplastic midbrain including brainstem (N/A) |
IUGR, clenched hands, echogenic kidneys | MRI | CSF disorder Posterior fossa |
| Dandy Walker malformation (HP:0001305) Agenesis corpus callosum (HP:0001274) Ventriculomegaly (HP:0002119) Midline cyst (N/A) Vermian hypoplasia (HP:0001320) Brainstem hypoplasia (HP:0007362) Excessive cortical malformation, possible tectal thickening (N/A) |
Bilateral anophthalmia, midface hypoplasia, multiple areas of scoliosis/kyphosis. | MRI | CSF disorder Posterior fossa Cortical disorder |
| Bilateral ventriculomegaly (HP:0002119) Hypoplastic cerebellum (HP:0001321) Absent corpus callosum (HP:0001274) Dandy Walker variant (HP:0001305) |
Right clubbed foot. Micrognathia. Echogenic bowel. | CSF disorder Midline defect Posterior fossa |
|
| Alobar holoprosencephaly (HP:0006988) Microcephaly <1%ile (HP:0000252) Prior pregnancy with holoprosencephaly and microcephaly. |
Cleft lip/palate, absent stomach, second pregnancy also with absent nose, left micropthalmia | Prior affected pregnancy | Midline defect |
| Bilateral ventriculomegaly (HP:0002119) Hypoplastic cerebellum (HP:0001321) |
Heart defect - double outlet right ventricle and VSD | CSF disorder Posterior fossa |
|
| Open neural tube defect (HP:0034237) | Cleft lip/palate, very low set ears (noted at chin), micrognathia, tetrology of fallot with pulmonary stenosis, VSD, polyhydramnios | Neural tube defect | |
| Midline intrahemispheric cyst (HP:0010576) Absent cavum septum pellucidum (HP:4000138) Absent corpus callosum (HP:0001274) |
None | MRI | Midline defect |
| Acrania/anencephaly (HP0030716, HP:0002323) Prior pregnancy with acrania/anencephaly. Family history of males with anencephaly. |
None | Prior affected pregnancy | Neural tube defect |
| Vein of galen malformation (HP:0030713) | None | MRI | |
| Absent corpus callosum (HP:0001274) Absent cavum septum pellucidum (HP:4000138) Teardrop shaped ventricles (HP:0002118) |
None | Midline defect | |
| Holoprosencephaly, semilobar to alobar (HP:0001360) | None | MRI | Midline defect |
| Unilateral ventriculomegaly (HP:0002119) Hypoplastic corpus callosum (HP:0002079) Possible schizencephaly (HP:0010636) Polymicrogryria (HP:0002126) |
None | MRI | CSF disorder Midline defect Cortical disorder |
| Absent corpus callosum (HP:0001274) Bilateral ventriculomegaly (HP:0002119) Absent cavum septum pellucidum (HP:4000138) |
None | CSF disorder Midline defect |
|
| Anencephaly HP:0002323 Prior pregnancy with anencephaly. | None | Prior affected pregnancy | Neural tube defect |
| Anencephaly HP:0002323 Prior pregnancy with encephalocele. |
None | Prior affected pregnancy | Neural tube defect |
| Polymicrogyria (HP:0002126) Bilateral ventriculomegaly (HP:0002119) |
None | Autopsy MRI |
CSF disorder Cortical disorder |
AV, atrioventricular; AVSD, atrioventricular septal defect; CDH, congenital diaphragmatic hernia; CSF, cerebrospinal fluid; d, day; FBA, fetal brain abnormality; IUFD, intrauterine fetal demise; IUGR, intrauterine growth restriction; MRI, magnetic resonance imaging; NOS, not otherwise specified; ONTD, open neural tube defect; SUA, single umbilical artery; VSD, ventricular septal defect; wk, week.
a
Prenatal FBA written as description from available phenotyping as well as associated HPO term, when available.
b
N/A denotes HPO term not available for this fetal phenotype. HPO terms do not include many prenatal specific phenotypes at this time.