2. z Classification of
Genetic disorder
Single gene
disorders
Chromosome
Disorder
Autosomal
Numeric Structural
Sex chromosome
Numeric Structural
Multifactor
disorder
Acquired
somatic Genetic
disease
3. z
CHROMOSOMAL ANOMALIES
Chromosomal anomalies = Missing , extra or irregular
portion of chromosomal DNA
Chromosomal anomalies are detected via karyotype
testing
Abnormalities depends on type of chromosome
affected due to non- disjunction chromosomes.
11. z
Antenatal ultrasound: general features
Intrauterine growth restriction (IUGR) tends to be early
Abnormal liquor volume : mostly polyhydramnios or oligo
Increased nuchal thickness
Evidence of hydrops fetalis
22. z
In the postnatal period, characteristic phenotypical features point to the diagnosis:
23. z
MARKERS:
Reduced
materanal serum
alpha fetoprotein
Reduced Estriol
Reduced beta
HCG
PATAU SYNDROME EDWARD SYNDROME DOWNS SYNDROME
• Reduced maternal
serum AFP
• Reduced maternal beta
HCG
• Reduced PAPP-A
• Reduced materanal
serum alpha
fetoprotein
• Reduced Estriol
• Reduced beta HCG
• Maternal free beta-
hCG: higher than
chromosomally normal fetuses
• inhibin A: higher than
chromosomally normal fetuses
• AFP: lower than
chromosomally normal
fetuses
• unconjugated estriol
(uE3): lower than
chromosomally normal
fetuses
24. z
STRUCTURAL AUTOSOMAL ANOMALIES :
CRI DU CHAT SYNDROME
Cri du chat syndrome is a rare congenital disorder caused by the deletion of
the short arm of chromosome 5.
A high-pitched monotonous cry is the characteristic finding.
The patient also usually has craniofacial malformations such as microcephaly,
bridge
Newborns also have microcephaly and have an increased risk of asphyxia
25. z
Prader-Willi and Angelman Syndrome
Prader-Willi Syndrome
Microdeletion of chromosome15
Lack of muscle tone in newborn
As adult – gross obesity
Radiographic features:
Abnormalities of calvarium and
sella turcica
Coxa valga
Scoliosis
Angelman Syndrome
Microdeletion of chromosome 15.
Development delay
Jerky movements
Stiff, fixed smile
Epilepsy
27. z
Klinefelter syndrome
Childhood:
Weaker muscles and reduced strength
Puberty:
• Tall stature ; long lower limbs, Rounder body type
• Testicular atrophy/Microorchidism( small testicles)
• Female pattern of pubic hair
Gynecomastia( increased breast tissue)
Azospermia leading to infertility
Micropenis
IQ is normal
• Serum testosterone levels low to normal
• FSH and LH levels very high
28. z
Radiographic features:
USG: Klinefelter syndrome should be suspected in postpubertal males with bilateral
symmetrical small testicular volume (usually 3~4 mL in volume) usually presented by
subfertility/primary infertility or assessment of small testicular size
29. z
TURNER SYNDROME
Absence of one chromosome x (45 XO )
Most common sex abnormality in females
GENE SHOX -> important for bone development and growth
Loss of one copy of this gene -> short stature
30. z
Clinical Findings
Normal intelligence
Ovaries develop normally at first but oocytes die
prematurely and most ovarian tissue degenerate
before birth
Heart defect ( coarctation of the aorta,
abnormalities of aortic valve )
Short stature -> becomes evident by about age 5
Webbed neck
31. z Radiological features:
Skeletal features -> inconstant and non specific
Decreased density of the skeleton ( esp . Hands and feet )
ANTENATAL ULTRASOUND
1. Cystic hygroma
2. Increased nuchal thickness
3. Increased nuchal translucency
4. Hydrops fetalis
5. Mild IUGR
6. Short fetal limbs
32. z
Nuchal translucency
INCREASED nuchal translucency
A finding during first trimester
Measured on saggital image through the fetal neck
Rate of aneuploidy when the nuchal thickness is < 2mm
--> less than 1 %
Back of neck
33. z
Nuchal thickness:
INCREASED nuchal thickness
Measured in a second trimester
Abnormal value > 6mm
Should not be measured after 20.6 weeks
Back of head
34. z Cystic hygroma
A cystic lymphatic lesion
Septation indicate poorer outcome
Volumes > 75mm3 correlate with increased
abnormality and poorer fetal outcome
35. z Hydrops fetalis
Excessive accumulation of fluid in fetal subcutaneous tissue or
atleast 2 fetal serous cavities
Fetal pleural effusion
Fetal pericardial effusion
Fetal ascites
Placental enlargement
Polyhydromnios
Fetal anasarca
36. z
Hand and feet :
Post partum and Adulthood
HAND:
1. Positive metacarpal sign
2. Increased carrying angle of elbow / cubitus
valgus.
FEET:
1. Abnormal medial tibial condyle -> depressed
and beak like
2. Abnormal medial femoral condyle -> project
downward
37. z
Positive metacarpal sign
A line drawn along the heads of 4 th and 5 th metacarpals will intersect the
head of the 3 rd metacarpal if shortening is present
38. z
Cubitus valgus
Increased carrying angle of the elbow
Carrying angle ( Cubital angle ) -> formed
between the humerus and the forearm axis
NORMAL – 5-15 degree away from the body
<5 degree : cubitus varus
>15 degree: cubitus valgus
41. z
Dd
TURNER’S SYNDROME DOWN SYNDROME
Normal intelligence Mental retardation
Cardiac defect : coartation of aorta, bicuspid
aortic valve
Cardiac defect: intracardial septal defect
Metacarpal sign
Cubitus valgus
Clinodactily
Mickey mouse pelvis ( large ilium)
Absence of last rib
Webbed neck Orbital hypo/ hypertelorism
Cystic hygroma
Increased Nuchal thickness
Increased Nuchal translucency
Cystic hygroma
Increased Nuchal thickness
Increased Nuchal translucency
42. z
GENOTYPE GENDER SYNDROME PHYSICAL TRAITS
XY MALE -
XXY MALE Klinefelter’s
syndrome
Sterility, small testicles, breast
enlargement
XYY MALE Jacob’s syndrome Normal male traits
XX FEMALE -
XO FEMALE Turner syndrome Sex organs don’t mature at
adolescence , sterility, short
stature
XXX FEMALE Triple X Tall stature , normal intelligence
with learning disabilities, limited
fertility
43. z
Chromosome
affected
Autosomes
Numeric
Autosomal
monosomy
Autosomal
Trisomies
Patau syndrome
Edward syndrome
Down syndrome
Structural
Deletions
1.Cri du chat
syndrome
2. Prader Willi
syndrome
3. Angelman
syndrome
Sex
chromosomes
Numeric
Autosomal
monosomy
Autosomal
trisomies
1. Klinefelter’s
syndrome
2. Jacob’s
syndrome
3. Triple x
syndrome
Structural
X linked
dominant
X linked
recessive
1.Alport
syndrome
2.Nephrogenic DI
3. Hypo-
phosphatemic
rickets
Turner’s
syndrome
(45 XO)
1. Colour
blindness
2. Duchenne
muscular
dystrophy
3.Hemophilia
SUMMARY
Karyotype = full set of chromosomes from an individual.
Non dysjunction can occur either during meiosis 1 or meiosis 2
numeric autosomal anomalies
Down ,Edward and down syndrome are the only three trisomies compatible with extrauterine life.
Normal upper lip
Cleft lip with cleft palate
Micropthalmia- small eyes
micrognathia- small mandible’
Hypotelorism- abnormal decrease in distance between 2 eyes
Cyclopia- single palpebral fissure and single midline orbit which may contain either a single globe or two separate globe.
Proboscis- anterior appendage like structure is seen projecting from the midline forehead
Polydactily in hand and feet.
Frontal radiograph of the hand showing polydactyly of the fifth finger ( post axial polydactyly – where additional digit is on the ulnar margin of hand or lateral to 5 th little toe )
SKELETAL ABNORMALITIES:
Polydactyly
Rock bottom feet
CNS ABNORMALITIES :
Holoprosencephaly is a disorder caused by failure
1.Holoprosencephaly – most commonly assosciated cns anomaly
In alobar holoprosencephaly, the thalami are fused and there is a single large posteriorly located ventricle. Most commonly associated with facial abnormalities
Semilobar holoprosencephaly
The basic structure of the cerebral lobes are present but are fused most commonly anteriorly and at the thalami
Monoventricle
Fused central thalami
Fused choroid plexus
4th ventricle
Nuchal edema- subcutaneous accumulation of extracellular fluid in fetal neck is detected as increased nuchal translucency (NT) by ultrasonography in 1 st trimester of pregnancy
LOBAR TYPE- RARE
1.holoprosencephaly
2. Microcephaly
3. Fetal hydrocephaly
4. Enlarged cisterna magna
4. Agenesis of corpus callosum
ABDOMINAL WALL ABNORMALITIES:
Omphalocele
Bladder exstrophy
Alfa feto protein
Pregnancy assosciated plasma protein A
Hydrops is defined as the accumulation of fluid +/- edema involving at least two fetal components,
fetal pleural effusion
fetal pericardial effusion
fetal ascites
generalized body edema: fetal anasarca/nuchal edema/cystic hygroma
placental enlargement
polyhydramnios
Flatennning of occipital bones
With relative hypoplasia of the frontal bones causing pointing of frontal lobes
Strawberry skull is seen associated with DOLICHOCEPHALY ( most common form of craniosynostosis ) where premature closure of sagittal suture results in impediment of lateral growth of the skull while anteroposterior growth continues , producing a classic elongated yet narrow skull
Hand abnormalities:
Clenched hands : with an overlap of 2 nd and 3 rd digits in 80%
Rocker bottom feet
Atrioventricular septal defect
Atrial septal defect
Ventricular septal defect
Hypoplastic appearing thorax with reduced lung volume - pulmonary hypoplasia
Extensive lung disease with interstitial thickening and cystic change peripherally. Perihilar collapse.
subpleural cysts bilaterally (small arrows). variable-sized cysts in the middle
Axial US image of a hypoplastic cerebellum with a transcerebellar diameter of 19 mm (at the 22 weeks of gestation, the 5th and 95th percentile the transcerebellar diameter is between 21.6 mm and 25 mm)
DEVELOPMENT DYSPLASIA OF HIP :
Hilgenreiner's line is drawn horizontally, connecting the inferior aspect of the tri-radiate cartilages bilaterally. The femoral head should be below this line
Perkin's line is drawn vertically though the lateral most aspect of the acetabular roof, perpendicular to Hilgenreiner's line. The ossified femoral head should be located in the inferomedial quadrant created.
Shenton line along the inferior aspect of the superior pubic ramus and the inferiomedial femoral neck.
The acetabular angle is measured between Hilgenreiner's line and a line parallel to the acetabular roof. At birth it should be less than 28 degrees, and should progressively reduce with maturation of the hip.
Classic "Mickey Mouse" appearance of the pelvis in Down syndrome with flared iliac wings.
Depressed nasal bridge and low set ears
Epicanthal folds
Abundant neck skin
Macroglossia
Simian crease( single palmar crease)
Pregnancy assosciated plasma protein A
Cri-du-chat syndrome
Micro deletion of chromosome 5
Di-George syndrome
Micro deletion of chromosome 22
Schizophrenia & Obsessive Compulsive Disorder
Micro deletion of chromosome 22 associated
Angelman syndrome
Micro deletion of chromosome 15
Prader-Willi syndrome
Micro deletion of chromosome 15
Both occur due to microdeletion of chromosome 15
Numeric sex chromosomal anomalies
Structural sex chromosomal anomalies.
It should be measured between 11- 13.6weeks
It should be measured between 14-21weeks
Cavum septum pellucidum
Thalami
Cerebellum
Cisterna magna
Nuchal fold thickness
Mc cardiovascular defect :
Bicuspid aortic valve
Coartation of aorta
Ultrasound showing streak ovaries with no follicles
Horse shoe kidney
Jacobs – normal physically and mentally , increase in testosterone and more aggressive