nt and aneuploidy
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Transcript of nt and aneuploidy
NT AND ANEUPLOIDY
.Monosomics for all human autosomes die in utero.A sex-chromosome monosomic complement of 44 autosomes + 1 X produces the phenotype of Turner syndrome.The most common type of viable human aneuploid is Down syndrome occurring at a frequency of about 0.15 percent of all live birthsThe only other human autosomal trisomy to survive to birth are afflicted with either trisomy 13 (Patau syndrome) or trisomy 18(Edwards syndrome). Trisomies chromosome 2, 16, and 22 are relatively common in abortuses but never survive to birth. Trisomy of the sex chromosomes is possible, such as in (47,XXX), (47,XXY), and (47,XYY).
NUCHAL TRANLUCENCY
USG MARKERS NT - MOST ROBUST MARKER NASAL BONE TRICUSPID FLOW DUCTUS VENOSUS FLOW
WHY FIRST TRIMESTER COMBINED SCREENING MA+NT+BIOCHEMICAL MARKERS Advantages compared to second trimester biochemical screening include: Earlier diagnosis (11-14 weeks) Higher detection rates for fetal Down syndrome (80-90% or perhaps even higher compared to 75% for the second trimester "quad" screen and 60-70% for the older "triple" screen) Detection of most major chromosome abnormalities other than trisomy 21 Acts as a nonspecific marker for other birth defects including some major cardiac defects and syndromic conditions Can detect a number of major structural birth defects associated with normal chromosomes The primary disadvantage is Narrow window of entry (11-14 weeks with ideal entry at 11-12 weeks).
NT AND ANEUPLODY
MATERNAL AGE + NTM A + NT + BIOCHEMICAL MARKERS
M A + NT + B M + NB/DV FLOW/TCV FLOW.
RISK 1 TO 50 NB –N NO CHANGE IN RISKRISK UPTO 1 TO 1000 NB- N RISK REDUCED NB-AB RISK INCREASEDHYPOPLASTIC NB ALL OTHER MARKERS N –REPEAT SCAN
REVERSE a WAVE RISK ALWAYS INCREASED
NT AND EUPLOID FETUS
INCREASED NT A/W INCREASED FETAL MORTALITY INCREASED NT A/W STRUCTURAL ABNORMALITIES
MAJOR CARDIAC DEFECTS DIAPHRAGMATIC HERNIA EXOMPHALOS SKELETAL DEFECTS BODY STALK ANOMALIES
Cardiac defectsDiaphragmatic herniaExomphalosAchondrogenesis type IIAchondroplasiaAsphyxiating thoracic dystrophyBeckwith-Wiedemann syndromeBlomstrand osteochondrodysplasiaBody Stalk anomalyCampomelic dysplasiaEEC syndromeFetal akinesia deformation sequenceFryn syndromeGM1-gangliosidosisHydrolethalus syndrome
Jarcho-Levin syndromeJoubert syndromeMeckel-Gruber syndromeNance-Sweeney syndromeNoonan syndromeOsteogenesis imperfecta type IIPerlman syndromeRoberts syndromeShort-rib polydactily syndromeSmith-Lemli-Optiz syndromeSpinal muscular atrophy type 1Thanatophoric dysplasiaTrigonocephaly 'C' syndromeVACTEREL associationZellweger syndrome
THE 11-14 WEEK SCAN
I Fetal abnormalities
ABNORMAL NT NORMAL FETUS
Normally nuchal translucencydisappears by 14 weeks.
Noteworthy are cases with abnormal NT that resolve spontaneously around 14 weeks and show healthy outcome
Chromosomally and structurally normal fetuses with history of thickened NT with no evidence of nuchal fold thickening or non-immune hydrops, at 20 weeks -- no increased risk for perinatal or long-term morbidity and mortality
Chromosomally and structurally normal fetuses with
Altered dermal collagen composition (eg, Down syndrome)
Abnormal nuchal lymphogenesis (eg, Turner syndrome)
Hemodynamic alterations and cardiac dysfunction( heartdefects)
Abnormal endothelial cell differentiation
PATHOPHSIOLOGY OF NT-
NASAL BONE ABSENT PRESENT
MAXILLO FACIAL ANGLE NORMAL REDUCED INCREASED TRISOMY 21
DUCTUS VENOSUS FLOW reverse a wave a/w chromosomal
defects cardiac defects and adverse fetal outcome
TRICUSPID FLOW Prevalence of TCV regurgitation in fetuses with trisomy 21 is about
74% whereas only 7% of chromosomally normal fetuses have this finding There is an increased prevalence of cardiac defects with TC regurgitation, irrespective of the presence or absence of aneuploidy
FETAL MEASUREMENTS AS MARKERS FETAL GROWTH/ CRL - REDUCED GROWTH CAN BE SEEN IN
TRISOMY 13 ,18, TURNERS SYNDROME HOWEVER NOT IN TRISOMY 21
FETAL HEART RATE -BRADYCARDIA SEEN IN TRISOMY 18 AND TRIPLOIDY AND TACYCARDIA IN TRISOMY 13 AND TURNER SYNDROME
FETAL STRUCTURAL DEFECTS AS MARKERS
SINGLE UMBILICAL ARTERY/ TWO VESSEL CORD SEVEN FOLD INCRESED RISK FOR TRISOMY 18
MEGACYSTIS MEGACYSTIS LONG. BLADDER OF >7MM 7-15 MM A/W INCREASED RISK OF TRISOMY 13 AND 18 EUPLOID FETUSES –SPONTANEOUS RESOLUTION >15 MM LESS LIKELY CHROMOSOMAL ANOMALIES MORE LIKELY TO CAUSE OBSTRUTIVE UROPATHY
OMPHALOCOELE HIGH ASSOCIATION WITH TRISOMY 18 ONE OF THE REASONS TO PERFORM NT SCREENING AT
11WEEKS NO PHSIOLOGICAL BOWEL HERNIATION
OMPHALOCOELES WITH ONLY BOWEL HERNIATION STRONGER ASSO. WITH ANEUPLOIDY
Aneuploid fetuses with omphalocoeles containing only bowel show resolution in significant no of fetuses, most likely developmental delay.
HOLOPROSENCEPHALY EXTREME FORM ALOBAR HOLOPROSENCEPHALY CAN BE
DETECTED IN FIRST TRIMESTER INCREASED RISK OF ANEUPLOIDY MOSTLY TRISOMY 13
THE FIRST TRIMESTER ANOMALY SCAN DETECTABLE ABNORMALITIES
THE FIRST TRIMESTER SCAN IS NO LONGER A NT SCAN BUT A
FETAL ANATOMY SCAN
INTRACRANIALTRANSLUCENCYIN OPEN NEURAL TUBE DEFECTS
a case of open spina bifid demonstrating compression of the fourth ventricle with no visible translucency.
The fourth ventricle presents as an intracranial translucency (IT)between the brain stem and the choroid plexus.
ARNOLD CHIARI 2Lemon sign: Scalloping of frontal bonesBanana sign: Caudal displacement of cerebellum , obliteration of CMNot consistently seen in first trimester.
POSTERIOR FOSSA AT 11 TO 13.6 WEEKS NORMAL POST FOSSA CYST OPEN
SPINA B
NEURAL TUBE DEFECTS Meningoenc Occipital (MC) – A/w skull defect (cf D/D Nuchal cystic hygrom Parietal Frontoethmoidal
A/w Microcephaly, Hydrocephalus, Spina bifida, Meckel Gruber Syn.
d/d : Cystic Hygroma
ACRANIA–EXENCEPHALY-ANENCEPHALY
SKULL OSSIFICATION AT 11 WEEKS OF OCCIPITAL BONE
Varying degrees of distortion of brain
MECKEL GRUBER SYNDROME Encephalocoele Polycystic kidneys Polydactyly
DANDY WALKER COMPLEX Complete or partial absence of cerebellar vermis 4th Ventricle Dilatation End point of chromosomal abn. , Genetic
Syndromes , congenital infection or Isolated abn
HYDRANENCEPHALY Total absence of cerebral hemispheres
Large head Small hemispheres Fluid-filled intracranial cavity
with no midline echoes
HOLOPROSENCEPHALY Alobar and Semilobar a/w facial abnormalities Lobar
INIENCEPHALY Rare Cervical dysraphism with
occipital(inion) defect + encephalocoele
Persistently extended fetal head -clue
CARDIAC ANOMALIES Fetal 4 chamber view can be demonstrated at 11to 14 weeks
scan
RAISED NT PERSISTENT BRADYCARDIA (60BPM) COMPLETE AV CANAL DEFECT
A 14 WEEK SPECIALIST SCAN CAN REVEAL MAJOR ABN OR RAISE SUSPICION FOR LATER DETAILED SCAN
4 CHAMBER VIEW AV CANAL DEFECTS VSD
MUSCULOSKELETAL ABN. CAUDAL REGRESSION SYNDROME DEGREES OF VERTEBRAL ANOMALIES FROM PERTIAL SACRAL
AGENESIS TO ABCENCE OF LUMBAR SPINE. 250 TIMES MORE COMMON IN POORLY CONTROLLED DIABETIC
MOTHERS
ABSENT LIMBS
BODY WALL ANOMALIES PHSIOLOGIC BOWEL HERNIATION
AT 9 TO 11 WEEKS
EXOMPHALOS - a/w CHROMOSOMAL DEFECTS .CORD INSERTION AT APEX OF SAC VS GASTROCHISIS PARA MIDLINE HERNIA SAC
URINARY ANOMALIES PYELECTASIS RANGE
MEGACYSTIS CYSTIC DYSPLASTIC KIDNEY RENAL AGENESIS POLYCYSTIC KIDNEYS
SECOND TRIMESTER FETAL ANOMALY
CARDIOVASCULAR ANOMALY
Fetal cardiac examinations optimally performed between 18-22 weeks.
Some anomalies may be identified in late first and early second trimester especially when increased nuchal translucency is identified.
4 chamber view, 3 vessel view and outflow tracts can detect 80% -85% of cardiac anomalies
four chamber view
BASIC VIEW
Right ventricular outflow tract(RVOT)
Left ventricular outflow tract(LVOT)
EXTENDED BASIC VIEWS
VSD• One of the most common congenital cardiac anomaly• VSD is easily diagnosed on the four-chamber view
alone. • However, color Doppler US may be needed to
demonstrate smaller defects and some may not be detected until after birth.
Small VSD (MUSCULAR)show spontaneous closure
ENDOCARDIAL CUSHION DEFECT When the endocardial cushions fail to fuse, a
wide range of atrioventricular septal defects occur.
(four-chamber view)shows absence of the interventricular and interatrialsepta, thus producing connectionsbetween the ventricles and between the atria.
PERSISTENT TRUNCUS ARTERIOSUS The undivided truncus receives blood from
both ventricles. A VSD is almost always present
a.(four-chamber view) shows a VSD (arrow). Dao descending aorta. b.(base view)shows a single trunk (arrow) overriding both ventricles.
HYPOLPASTIC LEFT HEART SYNDROME Small left ventricle, which is associated
with aortic atresia. Atretic or hypoplastic mitral valve.
Hypoplastic left heart syndrome in a fetus(four-chamber view) shows that the left ventricle issmall relative to the right ventricle and the left atrium issmall relative to the right atrium.
EBSTEIN ANOMALY CAUDALLY PLACED TRICUSPID VALVE /OFFSET BETWEEN MITRAL AND
TRICUSPID VALVE /ENLARGED RT VENTRICLE /TRICUSPID REGURGITATION
DOUBLE OUTLET RIGHT VENTRICLE PARALLEL OUTFLOW TRACTS , LARGE RT VENTRICLE ,SMALL LT
VENTRICLE
RHYTHM AMNORMALITIES OF HEART NORMAL HEART RATE 2ND IS 120BPM TO 160BPM FETAL ARRYTHMIAS can now be defined precisely for mechanism-
specific therapy and for subsequent monitoring of response.
MSK ANOMALIESFETAL SKELETAL STRUCTURES TO BE SEEN:FETAL CRANIUM(BPD, HC)ABDOMINAL CIRCUMFERENCE(AC)MANDIBLECLAVICLESCAPULACHEST CIRCUMFERENCEALL FETAL LONG BONES( RHIZOMELIA, MESOMELIA, MICROMELIA)FETAL FACIAL PROFILE(GLABELLAR BOSSING, FLATTENED NASAL BRIDGE, MICROGNATHIA)VERTEBRAL BODIESHAND AND FEET( EXTRA/MISSING/MALFORMED DIGITS)MINERALISATION PATTERN.CHEST:ABDOMEN CIRCUMFERENCE( <0.6 ABNORMAL)FL:AC RATIO(<0.16 ABNORMAL)FL: FOOT LENGTH RATIO(<1 ABNORMAL)
CONTD.. FETAL LONG BONES:
PRESENCE/CURVATURE/MINERALISATION/FRACTURES The femur length–abdominal circumference ratio (<0.16 suggests lung hypoplasia) femur length–foot length ratio(normal = 1, <1 suggests skeletal dysplasia) THORAX: CHEST CIRCUMFERENCE/ CT RATIO MEASURED AT THE
LEVEL OF FOUR CHAMBER VIEW OF HEART. HAND AND FEET: PRE AND POSTAXIAL
POLYDACTYLY/SYNDACTYLY/CLINODACTYLY/OTHER DEFORMITIES SKULL:HC/BPD/SHAPE/MINERALISATION/OSSIFICATION. FACIAL STRUCTURES:MICROGNATHIA/ SHORT UPPER LIP/ABNORMALLY
SHAPED EAR/FRONTAL BOSSING/CLOVERLEAF SKULL. PELVIS: HYPOPLASTIC ACETABULAE/FLAT ILIAC BONES.
FETAL SKELETAL DYSPLASIA LIMB DEFICIENCY: complete absence –
amelia, incomplete absence-meromelia.
lack of a normal hand and the abnormal soft tissue at the distal end of theforearm
THANATOPHORIC DYSPLASIA Disproportionate dwarfism with very short
extremities,which are bowed in type 1 and may be straight in type 2.
Thorax is narrow. Cloverleaf skull deformity is generally seen in type 2. Polyhydramnios is present in almost 50% of cases. Pulmonary hypoplasia.
telephone receiver–shapedfemur
hypoplastic thorax
OSTEOGENESIS IMPERFECTA Rib fractures Thin cortex in tubular bones, and, in more severe
cases thin shafts with fractures and bowing deformities.
The skull may be thinner than usual and the weight of the US probe may deform the head quite easily. In severe cases, the cranial vault has a wavy outline and is easily compressed.
OSTEOGENESIS IMPERFECTA
bone fractures anddeformities.
decreased skull ossification
irregularshape of the ribs a finding that also suggestsfractures.
CHONDRODYSPLASIA PUNCTATA
Craniofacial dysmorphismVery short humeri and relatively short femora Punctate calcification of epiphyses may be seen prenatally multiple contractures
DIASTROPHIC DYSPLASIA• diastrophic” implies twisting and describes the
twisted habitus in diastrophic dysplasia
short broad long bones bilateral clubfeet with limb shortening
bilateral clubfeet with limb shortening (arrowheads)and bilateral hitchhiker’s thumb (arrow)
?RACIAL VARIATION UNIFORMLY SMALL LONG BONES CASE OF SHORTENING OF LONG BONES MANIFESTED AFTER 20
WEEKS FEMUR FOOT RATIO .9 THORACIC CIRCUMFERENCE /AC AND CARDIAC THORAX
RATIOS
CONT
THORAX ABNORMALITIES Diaphragmatic hernia- Abdominal organs will be in the chest.
Fluid filled mass just behind the left atrium and ventricle.Suspicious if stomach not visualized in abdomen.shift in the mediastinumSmall abdominal circumferencePolyhydramnios
Peristalsis of bowel in fetal chest.
.
.
CCAM/ CPAM SOLID /CYSTIC/ MIXED MASS CAM can displace mediastinal structures with compression of
the heart and IVC.Generally unilateral involving a single lobe.Associated with Hydrops,polyhydramnios,
and pulmonary hypoplasia. Many times small with little mass effect
PULMONARY SEQUESTRIAN Well circumscribed,uniformly echogenic mass in the fetal thorax. May be associated with fetal hydrops and maternal polyhydramnios. Color-Doppler todetect the arterial supply from the descending aorta to the mass.d/d CCAM
TRACHEAL/ LARENGEAL ATRESIA
If trachea or larnx is partially or completely obstructed, fluid is secreted by the lungs cannot be expelled. So distended lung, appears hyperechogenic and bronchi become dilated. Associated with fetal ascites.
Echogenic Bowel
ECHOGENIC BOWEL To call it echogenic bowel the echogenicity should be equal to bone.IN THIRD TRIMESTER ECHOGENIC IS NORMAL AS MECONIUM IS ECHOGENIC50% CASES OF ISOLATED ECHOGENIC BOWEL RESOLVE OVER TIME
Truly echogenic bowel in a second-trimester fetus, differential diagnostic considerations include Cystic fibrosis Chromosomal abnormalities-look for morphological anomalies ,congenital infection and intraamniotic bleeding, a/w IUGR
MECONIUM PERITONITIS
ECHOGENIC GASTRIC DUPLICATION CYST
1/3RD CASES A/W OTHER ABNORMALITIES GI and SPINAL
FETAL MASSES
NEUROBLASTOMA Associated malformations are unusual. Neuroblastoma is
characteristically a heterogeneous solid mass with cystic components that displaces the adjacent kidney inferiorly and
laterally. . Spontaneous regression occurs in up to 40% of cases.
SUBDIAPHRAGMATIC EXTRALOBAR PULMONARY SEQUESTRATION
MESOBLASTIC NEPHROMA Arteriovenous shunting, Heart failure and Polyhydramnios are
common. Mesoblastic nephroma is benign, and postnatal nephrectomy is curative
CARDIAC MASSES MC RHABDOMYOMA A/W TUBEROUS SCLEROSIS
TERATOMAS SACROCOCCYGEAL TERATOMAS – MC .HIGHLY VASCULAR
RESULTANT VASCULAR STEAL CAUSES HYDROPS/ POLYHYDAMNIOS AND PRE MATURE DELIVERY
NECK TERATOMAS
FETAL GENITOURINARY ABN
ABNORMALITIES PRESENTING IN THIRD TRIMESTER
OESOPHAGEAL ATRESIA Prenatally, the diagnosis of esophageal atresia is suspected
when, in the presence of polyhydramnios (usually after 25 weeks), repeated ultrasonographic examinations fail to demonstrate the fetal stomach.
SMALL BOWEL OBSTRUCTION The lumens of the small bowel and colon do not normally
exceed 7 mm and 20 mm, respectively. Diagnosis of obstruction is usually made quite late in pregnancy (after 25 weeks), as dilatation of the intestinal lumen is slow and progressive. Jejunal and ileal obstructions are imaged as multiple fluid-filled loops of bowel in the abdomen.
OVARIAN CYSTS Fetal ovarian cysts are hormone-sensitive (human chorionic
gonadotropin from the pLacenta) and tend to occur after 25 weeks of gestation
cysts are benign and resolve spontaneously in the neonatal period
FUTURE DIRECTIONS
SCREENING AT 6 TO 10 WEEKS CRL GSD YSD FHR RECENT PAPER BY FMF HAS SHOWN A sonographically
detectable differences between euploid and trisomic embryos.