Fetal anomalies

Question 1

• Lateral to the umbilicus (usually on the right)
• This defect arises from the incomplete closure of the lateral folds of the embryo during the 6th week of gestation.
• No membrane covers the loops which float free in the amniotic fluids

Answer 1

• Gastroschisis
• Usually an isolated defect
• Only 5% of cases have other anomalies
• No increase in incidence in aneuploidy with isolated cases
• Amniocentesis not required in isolated cases
• Increase in cidence in young maternal age <20
• Association with amyoplasia and intestinal atresia

Question 2

• Midline defect with herniation of abdominal contents into the base of the umbilical cord
• Confined by an amnioperitoneal membrane

Answer 2

• Omphalocele
• High incidence of aneuploidy (30%) +18 and +13
• Incication for Amniocentesis
• 2/3 of other structural anomalies
• 1/3 are isolated

Question 3

• Omphalocele
• Macrosomia, macroglossia, nephromegaly
• Large placenta
• Polyhydramnios

Answer 3

• Beckwith-Wiedemann

Question 4

• Cause by failure of closure of the inferior part of the anterior abdominal wall
• 4 weeks: failure of migration of the mesenchymal cells between the ectoderm of the abdominal wall and cloaca

Answer 4

• Bladder exstrophy
• Associations: separation of pubic bones, low set umbilicus,abnormal genitalia

Question 5

• A short femur is one of the USS markers of what trisomy?

Answer 5

• Trisomy 21

Question 6

• Name the syndrome
• Short limbs/IUGR
• Growth retardation
• Hirsutism
• upper limb reduction defects
• synophrys, high arched eyebrows , long lashes
• short nose, anteverted nares

Answer 6

• Cornelia de Lange Syndrome
• Frequent findings are cardiac defects, GI dysfuction
• hearing loss, myopia
• cryptorchidism/hypoplastic genetalia
• autistic and self distructive tendencies
• heterozygous pathogenic variant in NIPBL, RAD21, or SMC3
• hemizygouspathogenic variant in HDAC8 or SMC1A

Question 7

• Name the syndrome
• IUGR and normal OFC
• relative macrocephaly
• triangular face, downturned mouth
• asymmetry

Answer 7

• Russell-Silver Syndrome
• Most have been shown to have maternal UDP 7

Question 8

• Name the syndrome
• Straight femora and clover leaf skull
• Caused by de novo dominant mutations in FGFR3
• Short limbs with rolls of redundant skin
• Narrow chest
• large head with prominant forehead and depressed nasal bridge

Answer 8

• Thanatophoric dysplasia type 2
• All have mutations in Lys650Glu

Question 9

• Name the syndrome
• Curved femora and variable craniosynostosis
• Caused by de novo dominant mutations in FGFR3
• Short limbs with rolls of redundant skin
• Narrow chest
• large head with prominant forehead and depressed nasal bridge

Answer 9

• Thanatophoric dysplasia type 1

Question 10

• Name the syndrome
• The limb length age usually on or above the 5th centile until 24 weeks
• Many do not present until the 3rd trimester
• HC is usually around the 95th centile
• trident hands and frontal bossing

Answer 10

• Achondroplasia
• Mutations in FGFR3
• 2 common mutations G1138A and G1138C
• Lead to increase activity of FGFR3
• Paternal age effct

Question 11

• Short Limbs
• deformed limbs
• bowing, angulation and or fractures
• dark blue sclera
• soft skull to palpation

Answer 11

• Perinatal lethal: Osteogenesis imperfecta (OI)
• type II
• COL1A1/2
• 60% does in first day; 80% within the first week
• frog leg position of legs
• Death from pulmonary insufficiency

Question 12

• Short Limbs
• Deformity and fracture of the long bones
• Skull is undermineralized assuming a globular shape
• Blood ALK PHOS level is extreamly low

Answer 12

• Infantile Hypophosphatasia
• AR condition
• sever deficiency of chondro-osseous mineralization
• mutations in the tissue non-specific alkaline phosphatase gene
• TNSALP on 1p34-36

Question 13

• Short limbs
• hitch hiker thumbs
• severe bilateral talipes (club foot)
• scoliosis, calcification of costal cartilages
• ear pinna cysts

Answer 13

• Diastrophic dysplasia
• AR
• Mutation in the sulphate transporter gene
• SLC26A2 (aka DTDST)

Question 14

• Bowed limbs
• Mostly tibia bowing
• Pierre-Robin sequence
• Laryngomalacia
• Sex reversal- haploinsufficiency of SRY-related SOX9
• rearrangements of 17q24-5 region

Answer 14

• Campomelic dysplasia
• skeletal dysplasia
• many die in the neonatal period
• short stature
• cervical instability
• cord compression
• hearing impairment

Question 15

• Congenital Diaphragmatic herinia
• mosaicism for isochromosome 12p
• present in skin fibroblast but not in blood lymphocytes

Answer 15

• Pallister-Killian syndrome (tetrasomy 12p)
• increase nucal translucency
• polyhydramnios
• rhizomelic limb shortening
• abnormal facial profile with prominant philtrum
• CVS or placental biopsy prefered over amniocentesis
• FISH and especially interphase FISH on non-cultured cells increase the probability of identifying the isochromosome