FamilyLabel Family 6

Family6PresentingHPOs HP:0000202, HP:0000347, HP:0001161, HP:0000157, HP:0002101, HP:0002324, HP:0030449

(Oral cleft, Micrognathia, Hand polydactyly, Tongue abnormality, Defective lobation of lungs, Hydranencephaly, Therapeutic abortion)

HPOsFreeText abnormal larynx/trachea, basal occipitoschisis/keyhole, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

FamilyNotHPOs n/a

NotHPOsFreeText true alobar or semilobar holoprosencephaly

CountryOrigin Finland

Ethnicity n/a

Race n/a

Family6PreviousTesting n/a

ProbandLabel Case 6a, Male

Case6aPresentingHPOs HP:0001627

(Congenital heart defect)

HPOsFreeText Crown-heel body length 17.5cm, body weight 149g

Case6aNotHPOs n/a

NotHPOsFreeText Uterus duplex

Case6aAddInfo induced abortion at 18+2wk gestational age

Case6b Female

Case6bPresentingHPOs HP:0001829, HP:0010066

(Foot polydactyly, Duplicated hallux)

HPOsFreeText crown-heel body length 22cm, body weight 170g, uterus duplex, "absence of the dorsal arch of the first and second cervical vertebrae and the pituitary"

Case6bNotHPOs n/a

Case6bAddInfo induced abortion at 19+6wk gestational age

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

FamilyAddInfo n/a

FamilyPMIDs n/a

Case9 Male, Finland

CasePresentingHPOs HP:0000202, HP:0000347, HP:0001829, HP:0010066, HP:0000157, HP:0002101, HP:0002324, HP:0010664, HP:0030449

(Oral cleft, Micrognathia, Hand polydactyly, Duplicated hallux, Tongue abnormality, Defective lung lobation, Hydranencephaly, Fused thalami, Therapeutic abortion)

HPOsFreeText Crown-heel body length 22cm, body weight 245g, brain weight 6g, abnormal larynx/trachea, occipitoschisis/keyhole, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus, duplicated central canal in lumbar spinal cord, posterior columns seem disorganized. The ventral horn shows normal-appearing motor neurons with an SMI-311 neurofilament immunostain.

CaseNotHPOs HP:0001161

(Hand polydactyly)

NotHPOsFreeText Uterus duplex, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 19+5wk gestational age

CasePMIDs n/a

Case14 Female, Finland

CasePresentingHPOs HP:0000347, HP:0001829, HP:0010066, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260

(Micrognathia, Foot polydactyly, Duplicated hallux, Defective lung lobulation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly)

HPOsFreeText Crown-heel body length 35.5cm, body weight 1162g, brain weight 153g, abnormal larynx/trachea, uterus duplex, hydrocephalus/open-book, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia in the Sylvian fissures , neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus, large hypothalamic hamartoma that covers the brainstem (Fig4:) consisting of slightly nodular areas of small, round, probably partly immature, neuronal, and possibly some oligodendroglial cells, capillaries, astroglial cells, and occasional larger pyramidal neuronal cells on hematoxylin and eosin stain.

CaseNotHPOs HP:0000202, HP:0001627, HP:0000157, HP:0007165

(Oral cleft, Congenital heart defect, Tongue abnormality, Periventricular neuronal heterotopia)

NotHPOsFreeText hydranencephaly/anencephaly, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo death at 20 minutes old, 33+5wk gestational age

CasePMIDs n/a

Case8 Male, Finland

CasePresentingHPOs HP:0000202, HP:0000347, HP:0001829, HP:0010066, HP:0001627, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260, HP:0030449

(Oral cleft, Micrognathia, Foot polydactyly, Duplicated hallux, Congenital heart defect, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly, Therapeutic abortion)

HPOsFreeText Crown-heel body length 20cm, Body weight 323g, abnormal larynx/trachea, hydrocephalus/open-book, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0001161, HP:0000157, HP:0007165

(Hand polydactyly, Tongue abnormality, Periventricular neuronal heterotopia)

NotHPOsFreeText Uterus duplex, hydranencephaly/anencephaly, leptomeningeal heterotopia, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 19+0wk gestational age

CasePMIDs n/a

Case3 Female, Finland

CasePresentingHPOs HP:0000347, HP:0010066, HP:0001829, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007165, HP:0030449

(Micrognathia, Duplicated hallux, Foot polydactyly, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Periventricular neuronal heterotopia, Therapeutic abortion)

HPOsFreeText crown-heel body length 17cm, body weight 103g, abnormal larynx/trachea, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia, hydrocephalus/open-book, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0000202, HP:0001627, HP:0000157, HP:0007260

(Oral cleft, Congenital heart defect, Tongue abnormality, Type II lissencephaly)

NotHPOsFreeText Uterus duplex, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 15+6wk gestational age

CasePMIDs n/a

Case18 Male, Finland

CasePresentingHPOs HP:0003826, HP:0000347, HP:0001627, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260

(Stillbirth, Micrognathia, Congenital heart defect, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly)

HPOsFreeText Crown-heel bodylength 45cm, body weight 2050g, brain weight 265g, abnormal larynx/trachea, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0000202, HP:0001161, HP:0001829, HP:0007165

(Oral cleft, Hand polydactyly, Foot polydactyly, Periventricular heterotopia)

NotHPOsFreeText Uterus duplex, neuroepithelial rosettes, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo stillbirth, 36+6wk gestational age

CasePMIDs n/a

Case5 Male, Finland

CasePresentingHPOs HP:0000347, HP:0001161, HP:0001829, HP:0000157, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260, HP:0030449

(Micrognathia, Hand polydactyly, Foot polydactyly, Tongue abnormality, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly, Therapeutic aboriton)

HPOsFreeText Crown-heel body length 22cm, body weight 315g, Toe polydactly with multiple extra toes, Abnormal larynx/trachea, Hydrocephalus/open-book, Occipitotemporal hypoplasia, Infratentorial hypoplasia, occipitotemporal hypoplasia, leptomeningeal heterotopia, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0000202, HP:0001627, HP:0002444, HP:0007165

(Oral cleft, Congenital heart defect, Hypothalamic hamartoma, Periventricular neuronal heterotopia)

NotHPOsFreeText Uterus duplex, hypothalamic hamartoma/bulging, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 18+1wk gestational age

CasePMIDs n/a

Case13 Female, 6day old death, Finland

CasePresentingHPOs HP:0000347, HP:0000157, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260, HP:0007165

(Micrognathia, Tongue abnormality, Defective lung lobulation, Hydrocephalus, Olfactory lobe aplasia, Callosal aplasia, Fused thalami, Polymicrogyria, Type II lissencephaly, Periventricular neuronal heterotopia)

HPOsFreeText Crown-heel body length 42cm, Body weight 2326g, brain weight 206g, abnormality larynx/trachea, uterus duplex, hydrocephalus/open-book, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus, small unilateral remnant of the olfactory tract, (Fig2:)small proximal stumps of callosal fibers with a small longitudinal Probst bundle element, lateral periventricular nodular heterotopia, smooth cortical surface without normal gyration; missing midline commissures , large leptomeningeal heterotopia between the ba and brain tissue surface immunopositive for microtubule-associated protein 2 (MAP-2), hypoplastic temporal lobe displays a miniature dentate fascia, dysplastic hippocampus, heterotopic (Fig5:) glioneuronal wart-like eruption, irregular and disrupted bundles of radial glial structures, calretinin (CR)-positive and reelin positive neurons in dysplastic cortex, (Fig6:) minute dysplastic inferior olive only in some neuronal groups, totally narrowed pyramid medially below in the right lower corner of the medulla oblongata, all layers are narrowed in the atrophic cerebellar cortex of HLS, short and small frontal bundle of Probst

CaseNotHPOs HP:0000202, HP:0001829, HP:0001627

(Oral cleft, Foot polydactyly, Congenital heart defect)

NotHPOsFreeText true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo 33+5wk gestational age

CasePMIDs n/a

FamilyLabel Family 6

Family6PresentingHPOs HP:0000202, HP:0000347, HP:0001161, HP:0000157, HP:0002101, HP:0002324, HP:0030449

(Oral cleft, Micrognathia, Hand polydactyly, Tongue abnormality, Defective lobation of lungs, Hydranencephaly, Therapeutic abortion)

HPOsFreeText abnormal larynx/trachea, basal occipitoschisis/keyhole, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

FamilyNotHPOs n/a

NotHPOsFreeText true alobar or semilobar holoprosencephaly

CountryOrigin Finland

Ethnicity n/a

Race n/a

Family6PreviousTesting n/a

ProbandLabel Case 6a, Male

Case6aPresentingHPOs HP:0001627

(Congenital heart defect)

HPOsFreeText Crown-heel body length 17.5cm, body weight 149g

Case6aNotHPOs n/a

NotHPOsFreeText Uterus duplex

Case6aAddInfo induced abortion at 18+2wk gestational age

Case6b Female

Case6bPresentingHPOs HP:0001829, HP:0010066

(Foot polydactyly, Duplicated hallux)

HPOsFreeText crown-heel body length 22cm, body weight 170g, uterus duplex, "absence of the dorsal arch of the first and second cervical vertebrae and the pituitary"

Case6bNotHPOs n/a

Case6bAddInfo induced abortion at 19+6wk gestational age

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

FamilyAddInfo n/a

FamilyPMIDs n/a

Case9 Male, Finland

CasePresentingHPOs HP:0000202, HP:0000347, HP:0001829, HP:0010066, HP:0000157, HP:0002101, HP:0002324, HP:0010664, HP:0030449

(Oral cleft, Micrognathia, Hand polydactyly, Duplicated hallux, Tongue abnormality, Defective lung lobation, Hydranencephaly, Fused thalami, Therapeutic abortion)

HPOsFreeText Crown-heel body length 22cm, body weight 245g, brain weight 6g, abnormal larynx/trachea, occipitoschisis/keyhole, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus, duplicated central canal in lumbar spinal cord, posterior columns seem disorganized. The ventral horn shows normal-appearing motor neurons with an SMI-311 neurofilament immunostain.

CaseNotHPOs HP:0001161

(Hand polydactyly)

NotHPOsFreeText Uterus duplex, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 19+5wk gestational age

CasePMIDs n/a

Case14 Female, Finland

CasePresentingHPOs HP:0000347, HP:0001829, HP:0010066, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260

(Micrognathia, Foot polydactyly, Duplicated hallux, Defective lung lobulation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly)

HPOsFreeText Crown-heel body length 35.5cm, body weight 1162g, brain weight 153g, abnormal larynx/trachea, uterus duplex, hydrocephalus/open-book, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia in the Sylvian fissures , neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus, large hypothalamic hamartoma that covers the brainstem (Fig4:) consisting of slightly nodular areas of small, round, probably partly immature, neuronal, and possibly some oligodendroglial cells, capillaries, astroglial cells, and occasional larger pyramidal neuronal cells on hematoxylin and eosin stain.

CaseNotHPOs HP:0000202, HP:0001627, HP:0000157, HP:0007165

(Oral cleft, Congenital heart defect, Tongue abnormality, Periventricular neuronal heterotopia)

NotHPOsFreeText hydranencephaly/anencephaly, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo death at 20 minutes old, 33+5wk gestational age

CasePMIDs n/a

Case8 Male, Finland

CasePresentingHPOs HP:0000202, HP:0000347, HP:0001829, HP:0010066, HP:0001627, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260, HP:0030449

(Oral cleft, Micrognathia, Foot polydactyly, Duplicated hallux, Congenital heart defect, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly, Therapeutic abortion)

HPOsFreeText Crown-heel body length 20cm, Body weight 323g, abnormal larynx/trachea, hydrocephalus/open-book, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0001161, HP:0000157, HP:0007165

(Hand polydactyly, Tongue abnormality, Periventricular neuronal heterotopia)

NotHPOsFreeText Uterus duplex, hydranencephaly/anencephaly, leptomeningeal heterotopia, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 19+0wk gestational age

CasePMIDs n/a

Case3 Female, Finland

CasePresentingHPOs HP:0000347, HP:0010066, HP:0001829, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007165, HP:0030449

(Micrognathia, Duplicated hallux, Foot polydactyly, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Periventricular neuronal heterotopia, Therapeutic abortion)

HPOsFreeText crown-heel body length 17cm, body weight 103g, abnormal larynx/trachea, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia, hydrocephalus/open-book, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0000202, HP:0001627, HP:0000157, HP:0007260

(Oral cleft, Congenital heart defect, Tongue abnormality, Type II lissencephaly)

NotHPOsFreeText Uterus duplex, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 15+6wk gestational age

CasePMIDs n/a

Case18 Male, Finland

CasePresentingHPOs HP:0003826, HP:0000347, HP:0001627, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260

(Stillbirth, Micrognathia, Congenital heart defect, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly)

HPOsFreeText Crown-heel bodylength 45cm, body weight 2050g, brain weight 265g, abnormal larynx/trachea, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0000202, HP:0001161, HP:0001829, HP:0007165

(Oral cleft, Hand polydactyly, Foot polydactyly, Periventricular heterotopia)

NotHPOsFreeText Uterus duplex, neuroepithelial rosettes, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo stillbirth, 36+6wk gestational age

CasePMIDs n/a

Case5 Male, Finland

CasePresentingHPOs HP:0000347, HP:0001161, HP:0001829, HP:0000157, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260, HP:0030449

(Micrognathia, Hand polydactyly, Foot polydactyly, Tongue abnormality, Defective lung lobation, Hydrocephalus, Olfactory lobe agenesis, Callosal agenesis, Fused thalami, Polymicrogyria, Type II lissencephaly, Therapeutic aboriton)

HPOsFreeText Crown-heel body length 22cm, body weight 315g, Toe polydactly with multiple extra toes, Abnormal larynx/trachea, Hydrocephalus/open-book, Occipitotemporal hypoplasia, Infratentorial hypoplasia, occipitotemporal hypoplasia, leptomeningeal heterotopia, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus

CaseNotHPOs HP:0000202, HP:0001627, HP:0002444, HP:0007165

(Oral cleft, Congenital heart defect, Hypothalamic hamartoma, Periventricular neuronal heterotopia)

NotHPOsFreeText Uterus duplex, hypothalamic hamartoma/bulging, true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo induced abortion at 18+1wk gestational age

CasePMIDs n/a

Case13 Female, 6day old death, Finland

CasePresentingHPOs HP:0000347, HP:0000157, HP:0002101, HP:0000238, HP:0001341, HP:0007370, HP:0010664, HP:0002126, HP:0007260, HP:0007165

(Micrognathia, Tongue abnormality, Defective lung lobulation, Hydrocephalus, Olfactory lobe aplasia, Callosal aplasia, Fused thalami, Polymicrogyria, Type II lissencephaly, Periventricular neuronal heterotopia)

HPOsFreeText Crown-heel body length 42cm, Body weight 2326g, brain weight 206g, abnormality larynx/trachea, uterus duplex, hydrocephalus/open-book, occipitotemporal hypoplasia, infratentorial hypoplasia, occipitoschisis/keyhole, leptomeningeal heterotopia, neuroepithelial rosettes, absent developed and identifiable mamillary bodies, absent anterior commissure, difficult to identify nucleus dentatus, small unilateral remnant of the olfactory tract, (Fig2:)small proximal stumps of callosal fibers with a small longitudinal Probst bundle element, lateral periventricular nodular heterotopia, smooth cortical surface without normal gyration; missing midline commissures , large leptomeningeal heterotopia between the ba and brain tissue surface immunopositive for microtubule-associated protein 2 (MAP-2), hypoplastic temporal lobe displays a miniature dentate fascia, dysplastic hippocampus, heterotopic (Fig5:) glioneuronal wart-like eruption, irregular and disrupted bundles of radial glial structures, calretinin (CR)-positive and reelin positive neurons in dysplastic cortex, (Fig6:) minute dysplastic inferior olive only in some neuronal groups, totally narrowed pyramid medially below in the right lower corner of the medulla oblongata, all layers are narrowed in the atrophic cerebellar cortex of HLS, short and small frontal bundle of Probst

CaseNotHPOs HP:0000202, HP:0001829, HP:0001627

(Oral cleft, Foot polydactyly, Congenital heart defect)

NotHPOsFreeText true alobar or semilobar holoprosencephaly

CasePreviousTesting n/a

Variant NM_145014.2(HYLS1):c.632A>G (p.Asp211Gly), homozygous

ClinVar 1143

gnomAD MAF= 0.009594(European(Finnish)), no homozygotes

CaseAddInfo 33+5wk gestational age

CasePMIDs n/a