Table 2 Fetal molecular diagnoses

30-P

ACTA1

c.116G>A (p.R39H)

[NM_001100]

AD/de novo het

NR

NR

RES

Nemaline myopathy 3 [MIM: 161800]; Myopathy, congenital, with fiber-type disproportion 1 [MIM: 255310]

24-P

ADGRG6

c.2677C>T (p.R893X)

[NM_020455]

AR/homozygous

Reproductive planning

NR

25%

Lethal congenital contracture syndrome 9 [MIM: 616503]

8-P

ALG12

c.437G>A (p.R146Q)

c.930_931delAC (p.R311fs)

[NM_024105]

AR/compound het

Reproductive planning

NR

25%

Congenital disorder of glycosylation type 1G [MIM: 607143]

111-T

AR

c.1814A>G (p.D605G)

[NM_000044]

XL/hemizygous (maternally inherited)

Reproductive planning

Recurrence risk

Unknown

50% (males)

Complete androgen insensitivity syndrome [MIM: 300068]

43-PRE

C5orf42

c.3667C>T (p.Q1223X)

c.1372-2A>G

[NM_023073]

AR/compound het

NR

NR

25%

Orofaciodigital syndrome 6 [MIM: 277170]; Joubert syndrome 17 [MIM: 614615]

87-PRE

CHRNG

c.136C>T (p.R46X)

c.459dupA (p.V154fs)

[NM_005199]

AR/compound het

NR

NR

25%

Multiple pterygium syndrome, lethal type [MIM: 253290]; Multiple pterygium syndrome, Escobar variant [MIM: 265000]

80-T

COL11A1

c.2739_2747del (p.P914_G916del)

[NM_001854]

AD/de novo het

NR

NR

RES

Stickler syndrome 2 [MIM: 604841]; Marshall syndrome [MIM: 154780]; Fibrochondrogenesis 1 [MIM: 228520]

17-P

COL1A1

c.2110G>A (p.G704S)

[NM_000088]

AD/de novo het

NR

NR

RES

Osteogenesis imperfecta (OI) types 1–4 [MIM: 166200, 166210, 259420, 166220]; Caffey disease [MIM: 114000]; Ehlers-Danlos syndrome 1 and 7a [MIM: 130000, 130060]

49-T

COL1A1

c.2533G>A (p.G845R)

[NM_000088]

AD/de novo het

Recurrence risk

Up to 25%

RES

Osteogenesis imperfecta (OI) types 1–4 [MIM: 166200, 166210, 259420, 166220]; Caffey disease [MIM: 114000]; Ehlers-Danlos syndrome 1 and 7a [MIM: 130000, 130060]

90-PRE

COL1A1

c.2164G>A (p.G722S)

[NM_000088]

AD/de novo het

Medical management

Reproductive planning

Recurrence risk

Up to 25%

RES

Osteogenesis imperfecta (OI) types 1–4 [MIM: 166200, 166210, 259420, 166220]; Caffey disease [MIM: 114000]; Ehlers-Danlos syndrome 1 and 7a [MIM: 130000, 130060]

65-PRE

COL1A2

c.1378G>A (p.G460S)

[NM_000089]

AD/de novo het

Recurrence risk

Up to 50%

RES

Osteogenesis imperfecta types 2–4 [MIM: 166210, 259420, 166220]; Ehlers-Danlos syndrome types 7B and cardiac valvular [MIM: 130060, 225320]

66-PRE

COL1A2

c.2576G>A (p.G859D)

[NM_000089]

AD/de novo het

NR

NR

RES

Osteogenesis imperfecta types 2–4 [MIM: 166210, 259420, 166220]; Ehlers-Danlos syndrome types 7B and cardiac valvular [MIM: 130060, 225320]

53-P

COL4A1

c.2879G>T (p.G960V)

[NM_001845]

AD/inherited het (mosaic mother)

Reproductive planning

NR

Up to 50%

Brain small vessel disease with hemorrhage [MIM: 607595]; Hereditary angiopathy with nephropathy aneurysms and muscle cramps [MIM: 611773]; Porencephaly 1 [MIM: 175780];

122-T

DDX3X

c.1703C>T (p.P568L)

[NM_001193416]

XL, de novo het

NR

NR

RES

Mental retardation, X-linked 102 [MIM: 300958]

7-P

DOK7

c.437C>T (p.P146L)

c.514G>A (p.G172R)

[NM_173660]

AR, compound het

NR

NR

25%

Fetal akinesia deformation sequence [MIM: 208150]; Myasthenia, limb-girdle, familial [MIM: 254300]

101-PRE

DVL1

c.1519delT (p.W507fs)

[NM_004421]

AD/de novo het

NR

NR

RES

Robinow syndrome, autosomal dominant 2 [MIM: 616331]

95-P

DYNC2H1

c.10885C>T (p.R3629X)

c.11230C>T (p.L3744F)

[NM_001080463]

AR/compound het

NR

NR

25%

Short-rib thoracic dysplasia 3 [MIM: 613091]

22-P

EIF2B2

c.586C>T (p.P196S)

c.599G>T (p.G200V)

[NM_014239]

AR/compound het

NR

NR

25%

Leukodystrophy with vanishing white matter [MIM: 603896]

81-PRE

FBN1

c.3299G>T (p.G1100V)

[NM_000138]

AD/de novo het

NR

NR

RES

Marfan syndrome [MIM: 154700]; Geleophysic dysplasia 2 [MIM: 614185] MASS syndrome [MIM:604308]; Ectopia lentis, familial [MIM:129600]; Acromicric dysplasia [MIM:102370]; Marfan lipodystrophy syndrome [MIM: 616914]; Weill-Marchesani syndrome 2 [MIM: 608328]; Stiff skin syndrome [MIM:184900]

60-T

FRMD4A

c.2723C>T (p.S908L)

[NM_018027]

AR/homozygous

NR

NR

25%

Agenesis of corpus callosum, with facial anomalies and cerebellar ataxia [MIM: 616819]

88-PRE

GLI3

c.3324C>G (p.Y1108X)

[NM_000168]

AD/de novo het

NR

NR

RES

Pallister-Hall syndrome [MIM: 146510]; Greig cephalopolysyndactyly syndrome [MIM: 175700]; Polydactyly types A1 and B [MIM: 174200]; Polydactyly, type IV [MIM: 174700]

74-PRE

HCCS

c.308_309insAGT (p.V103dup)

[NM_005333]

XL/de novo het

NR

NR

RES

Linear skin defects with multiple congenital anomalies [MIM: 309801]

114-T

IFT80

c.721G>C (p.G241R)

[NM_020800]

AR/homozygous

Reproductive planning

Recurrence risk

Unknown

25%

Short-rib thoracic dysplasia 2 with or without polydactyly [MIM: 611263]

96-P

INTU

c.1259+5G>T

c.1714C>T (p.R572X)

[NM_015693]

AR/compound het

NR

NR

25%

Ciliopathy with features of short-rib polydactyly syndrome

6-P

KMT2D

c.6617dupC (p.A2207fs)

[NM_003482]

AD/de novo het

Reproductive planning

Recurrence risk

Unknown

RES

Kabuki syndrome type 1 [MIM: 147920]

45-P

KMT2D

c.1967delT (p.L656fs)

[NM_003482]

AD/ het

(biological parents unavailable, gamete donors used)

Medical management

Recurrence risk

Up to 25%

~ 0%

(unless same donors used again)

Kabuki syndrome type 1 [MIM: 147920]

48-PRE

KMT2D

c.15680_15693dup (p.I5232fs)

[NM_003482]

AD/de novo het

NR

NR

RES

Kabuki syndrome type 1 [MIM: 147920]

126-PRE

KMT2D

c.5707C>T (p.R1903X)

[NM_003482]

AD/de novo het

NR

NR

RES

Kabuki syndrome type 1 [MIM: 147920]

55-PRE

KRAS

c.149C>T (p.T50I)

[NM_004985]

AD/de novo het

NR

NR

RES

Noonan syndrome 3 [MIM: 609942]; Cardiofaciocutaneous syndrome [MIM: 115150]

63-PRE

LAMC3

c.4415G>A (p.R1472Q)

c.4477+1G>A

[NM_006059]

AR/compound het

NR

NR

25%

Cortical malformations occipital [MIM: 614115]

47-T

MID1

c.673_674delAG (p.S225X)

[NM_000381]

XL/hemizygous (inherited from mildly affected mother)

NR

NR

50% (males)

Opitz GBBB syndrome 1 [MIM: 300000]

67-PRE

MYH3

c.2015G>A (p.R672H)

[NM_002470]

AD/inherited het (mosaic mother)

NR

NR

Up to 50%

Arthrogryposis, distal types 2A, 2B, 8 [MIM: 193700, 601680, 178110]

20-P

NDUFAF5

c.29T>A (p.L10X)

c.782T>G (p.M261R)

[NM_024120]

AR/compound het

Reproductive planning

Other (see Results)

25%

25%

Mitochondrial complex I deficiency [MIM: 252010]

1-P

NIPBL

c.459-2A>G

[NM_133433]

AD/de novo het

Recurrence risk

Unknown

RES

Cornelia de Lange syndrome type 1 [MIM: 122470]

112-PRE

P3H1

c.12delC (p.R4fs)

[NM_022356]

AR/homozygous

Reproductive planning

Recurrence risk

25–50%

25%

Osteogenesis imperfecta 8 [MIM: 610915]

13-P

PEX1

c.2097dupT (p.I700fs)

c.3205C>T (p.Q1069X)

[NM_000466]

AR/compound het

Reproductive planning

NR

25%

Peroxisome biogenesis disorder types 1A, 1B [MIM: 214100, 601539]

46-PRE

PKD1L1

c.6473+2_6473+3del

[NM_138295]

AR/homozygous

NR

NR

25%

Heterotaxy, visceral, 8, autosomal [MIM: 617205]

85-PRE

PTPN11

c.227A>T (p.E76V)

[NM_002834]

AD/de novo mosaic

NR

NR

0%

Noonan syndrome 1 [MIM: 163950]; LEOPARD syndrome 1 [MIM: 151100]; Metachondromatosis [MIM: 156250];

144-PRE

PTPN11

c.854T>C (p.F285S)

[NM_002834]

AD/de novo het

Reproductive planning

NR

RES

Noonan syndrome 1 [MIM: 163950]; LEOPARD syndrome 1 [MIM: 151100]; Metachondromatosis [MIM: 156250]

84-PRE

RAPSN

c.1166+1G>C

[NM_005055]

AR/homozygous

NR

NR

25%

Fetal akinesia deformation sequence [MIM: 208150]; Myasthenic syndrome, congenital, 11 [MIM: 616326]

69-PRE

RIT1

c.246T>G (p.F82L)

[NM_006912]

AD/de novo het

NR

NR

RES

Noonan syndrome 8 [MIM: 615355]

18-P

RYR1

c.14344G>A (p.G4782R)

c.14512-1G>A

[NM_000540]

AR/compound het

Medical management

Reproductive planning

25%

25%

Central core disease of muscle [MIM: 117000]

133-PRE

SOS1

c.1655G>A (p.R552K)

[NM_005633]

AD/de novo het

NR

NR

RES

Noonan Syndrome 4 [MIM: 610733]

11-P

TMEM67

c.1319G>A (p.R440Q)

c.233G>A (p.C78Y)

[NM_153704]

AR/compound het

Reproductive planning

25%

25%

Meckel syndrome 3 [MIM: 607361]; Joubert syndrome 6 [MIM: 610688]; Bardet-Biedl syndrome [MIM: 209900]; COACH syndrome [MIM: 216360]; Nephronophthisis 11 [MIM: 613550]

44-PRE

TUBA1A

c.1118G>A (p.R373K)

[NM_006009]

AD/de novo het

Reproductive planning

Unknown

RES

Lissencephaly type 3 [MIM: 611603]

21-P

WDR19

c.275T>G (p.L92X)

c.880G>A (p.G294R)

[NM_025132]

AR/compound het

Medical management

Reproductive planning

Recurrence risk

Up to 25%

25%

Short-rib thoracic dysplasia 5 [MIM: 614376]; Cranioectodermal dysplasia 4 [MIM: 614378]; Nephronophthisis 13 [MIM: 614377]