USG OF FETAL SYNDROMES DR NITIN WADHWANI

1. ULTRASOUND FEATURES
OF
FETAL SYNDROMES

2. Maternal Infections
• Fetal Cytomegalovirus Infection
• Fetal Parvovirus B19 Infection
• Fetal Rubella Syndrome
• Fetal Syphilis
• Fetal Toxoplasmosis Syndrome
• Fetal Varicella Zoster
Teratogens
• Fetal Alcohol Syndrome/Fetal Alcohol Effects
• Fetal Valproic Acid Syndrome
• Fetal Warfarin Syndrome
• Maternal Diabetes/Caudal Regression Syndrome
Central Nervous System
• Aicardi Syndrome
• Meckel Syndrome
• Lissencephaly
• Septo-optic Dysplasia
• Tuberous Sclerosis
• L1 Syndrome
Cranium/Face
• Craniosynostoses
• Facial Anomalies
Musculoskeletal System
• Skeletal Dysplasias
• Other Lethal Skeletal Dysplasias
• Vertebral Anomalies
• Upper Extremity Anomalies
• Lower Extremity Anomalies
Thorax
• Congenital High Airway Obstruction Syndrome
• Cornelia de Lange Syndrome
• Donnai-Barrow Syndrome
• Fryns Syndrome
• Pallister-Killian Syndrome
• Scimitar Syndrome
Heart
• 22q11.2 Deletion Syndrome
• Alagille Syndrome
• CHARGE Syndrome
• Heterotaxy Syndromes
• Holt-Oram Syndrome
• Noonan Syndrome
• Pentalogy of Cantrell
• Tuberous Sclerosis
Gastrointestinal System/Abdominal Wall
• Gastrointestinal System Disorders
• Abdominal Wall Defects

3. Genitourinary Tract
• Renal Tract Anomalies
• Genital Anomalies
Abnormal Fetal Movement
• Antley-Bixler Syndrome
• Caudal Regression Syndrome
• Congenital Ichthyosis
• Congenital Myasthenic Syndromes
• Congenital Myotonic Dystrophy, Type 1
• Fetal Akinesia
• Freeman-Sheldon Syndrome
• Prader-Willi Syndrome
Fetal Overgrowth
• Bannayan-Riley-Ruvalcaba Syndrome
• Beckwith-Wiedemann Syndrome
• Klippel-Trenaunay Syndrome
• Megalencephaly-Polymicrogyria-Polydactyly-
Hydrocephalus Syndrome
• Perlman Syndrome
• Proteus Syndrome
• Simpson-Golabi-Behmel Syndrome
• Sotos Syndrome
• Weaver Syndrome
Fetal Growth Restriction
• Russell-Silver Syndrome
• Seckel Syndrome
Microdeletion Syndromes
• Deletion 4p (Wolf-Hirschhorn
Syndrome)
• Deletion 5p (Cri du Chat Syndrome)
• Deletion 11q (Jacobsen Syndrome)
• Deletion 22q11.2 (DiGeorge Syndrome)
Metabolic Syndromes
• Neu-Laxova Syndrome
• Smith-Lemli-Opitz Syndrome
• Zellweger Syndrome
Other Malformations
• Amniotic Band Sequence
• VACTERL Association

5. MATERNAL INFECTIONS
1. Fetal Cytomegalovirus Infection
2. Fetal Parvovirus B19 Infection
3. Fetal Rubella Syndrome
4. Fetal Syphilis
5. Fetal Toxoplasmosis Syndrome
6. Fetal Varicella Zoster

6. Definition
Fetal cytomegalovirus (CMV) infection is a congenital disorder
characterized by
• hydrops,
• ascites, and
• ventriculomegaly
caused by transplacental transmission of CMV to the fetus.
The double-stranded DNA herpes group virus causes a mild infection or a
mononucleosis-type illness in young healthy adults, chronic disease in older
adults, and mild to severe congenital infection.
Synonym
Also known as congenital cytomegalovirus infection.
Etiology
Cytomegalovirus (a double-stranded DNA herpes group virus.
owl-eye
inclusions
Fetal Cytomegalovirus Infection

7. Diagnosis
Most features can be found by sonography beginning at approximately 20 weeks’ gestation.
Suggestive findings include:
• intracranial calcifications and intracranial hemorrhage,
• microcephaly,
• abnormal periventricular echogenicities,
• intraparenchymal foci,
• ventriculomegaly,
• intraventricular adhesions,
• periventricular pseudocysts,
• hypoplastic corpus callosum,
• cerebellar and cisterna magna abnormalities,
• signs of striatal artery vasculopathy,
• splenomegaly,
• occlusion of the foramen ovale,
• ascites,
• hyperechoic bowel,
• fetal growth restriction, and
• oligohydramnios.
 PCR testing of amniocentesis samples should be performed after a 6-week interval following the diagnosis of maternal infection and
is most sensitive after 21 weeks’ gestation.

8. FIG 1
FIG 5
FIG 2
FIG 3
FIG 4

9. FIG

11. Fetal Parvovirus B19 Infection
Definition
Infection with parvovirus B19 causes erythema infectiosum
characterized by
• “slapped cheek” facial appearance and
• lacy erythematous rash on the trunk and extremities.
Synonym
Also known as fifth disease.
Etiology
Acute maternal parvovirus B19 viremia leads to transplacental passage of the B19
virus and subsequent fetal infection.
Incidence
Acute parvovirus B19 infection occurs in 3% to 4% of pregnant women, with the
highest infection rates in school teachers and day care workers.

12. Diagnosis
Acute maternal parvovirus infection can be diagnosed by positive IgM
serologic findings; IgM can be detected 10 days after infection and may
persist for 3 months or longer.
IgM can be falsely negative, however, and failure to detect IgM
antibodies therefore does not rule out B19 infection.
Parvovirus B19 IgG develops several days after IgM and indicates past
infection. Maternal B19 viremia can also be confirmed by PCR with
improved sensitivity.
Fetal parvovirus infections can be confirmed by PCR for B19 DNA in
amniotic fluid.
Differential Diagnosis
Differential diagnosis includes other conditions leading to nonimmune
hydrops in the fetus.

13. Fetal Rubella Syndrome
Definition
Fetal rubella syndrome is a congenital disorder resulting from primary maternal infection with the rubella virus.
It is characterized by
• deafness,
• mental retardation,
• congenital cataract,
• heart defects, and
• other structural anomalies.
Synonyms
Synonyms for fetal rubella syndrome are fetal rubella effects, congenital rubella syndrome, and German measles.
Etiology
Fetal rubella is caused by an RNA togavirus, which is the only member of the genus Rubivirus. The fetus is infected
by transplacental transmission followed by hematogenous spread.

14. Diagnosis
The most frequent sonographic findings are
• cardiac malformations (in particular, septal defects),
• eye defects (cataracts, microphthalmia, and retinopathy),
• microcephaly,
• hepatomegaly, splenomegaly, and growth restriction.
The risk of congenital defects is limited to maternal infection during the first 16 weeks of pregnancy.
Sensorineural hearing loss and developmental delay are also associated with congenital rubella sydrome.
Associated Anomalies
Occasionally, the following anomalies can be associated with the classic findings of fetal rubella syndrome:
renal disorders, hypospadias, cryptorchidism, meningocele, glaucoma, patent ductus arteriosus, and peripheral
pulmonary stenosis.
Differential Diagnosis
Other conditions associated with congenital hepatomegaly and cataracts should be considered.
This includes other congenital infections (TORCH [toxoplasmosis, other infections, rubella, cytomegalovirus,
herpes simplex]), fetal anemia, fetal liver tumors, chondrodysplasia punctata, Neu-Laxova syndrome (NLS),
Smith-Lemli-Opitz (SLO) syndrome, and Walker-Warburg syndrome.

16. Fetal Syphilis
Definition
Fetal syphilis is caused by fetal infection with the spirochete Treponema pallidum,
which readily crosses the placenta leading to fetal infection.
Synonym
A synonym for fetal syphilis is congenital syphilis.
Etiology
Maternal infection with T. pallidum leads to transplacental transmission of the virus
and resultant fetal infection.
Incidence
Transmission can occur at any gestational age.
The frequency of vertical transmission increases as gestation advances but severity
decreases with infection later in pregnancy.
FIG. Syphilis. Darkfield micrograph
of Treponema pallidum, the
organism that causes congenital
syphilis.

17. Diagnosis
In women with positive syphilis testing, clinical findings concerning for congenital
syphilis include growth restriction, as well as liver and placental findings.
Signs of liver dysfunction include hepatomegaly and ascites, which can lead to
nonimmune hydrops.
The placenta is typically large and edematous.
Silver-staining of the placenta following delivery is positive for spirochetes.
Fetal serologic tests are positive for anti-treponemal IgM.
Associated Anomalies
Clinical findings in neonates may include the following:
1. Early congenital syphilis: hepatomegaly, syphilitic rhinitis (“snuffles”),
maculopapular rash, generalized lymphadenopathy, and skeletal abnormalities.
2. Late congenital syphilis: (generally a result of gumma formation in various
tissues): facial features (frontal bossing, saddle nose, short maxilla), eye findings
(interstitial keratitis, glaucoma, corneal scarring, optic atrophy), sensorineural
hearing loss, Hutchinson teeth, mulberry molars, perforation of hard palate,
rhagades, gummas, anterior bowing of shins (“saber shins”), and paroxysmal
cold hemoglobinuria.

19. Fetal Toxoplasmosis Syndrome
Definition
Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii.
Acute infections in pregnant women can be transmitted to the fetus and cause severe illness (mental retardation,
blindness, and epilepsy).
Etiology
Fetal toxoplasmosis is caused by transplacental transmission of parasites following maternal primary infection.
The rate of fetal transmission increases greatly as the gestational age at time of seroconversion increases, with
transmission rates of 25%, 54%, and 65%, in the first, second, and thirdtrimesters, respectively

20. Diagnosis
The classic triad suggestive of congenital toxoplasmosis includes
• chorioretinitis,
• intracranial calcifications, and
• hydrocephalus.
Less common findings include ascites, pericardial and pleural effusions, and
intrahepatic densities.
However, most infants infected in utero are born with no obvious signs of
toxoplasmosis on routine examination, but many develop learning and visual
disabilities later in life.
Other findings include microcephaly, encephalomyelitis, seizures, intellectual
disability, ascites, and hepatosplenomegaly.
The diagnosis can be made by using PCR to detect of Toxoplasma gondii in
amniotic fluid, with increased sensitivity later in pregnancy.
Differential Diagnosis
Other TORCH infections should be considered.

21. Fetal Varicella Zoster
Definition
Fetal varicella zoster is characterized by abnormalities
of multiple organs caused by fetal infection
with varicella following maternal chickenpox infection.
Synonyms
Fetal varicella zoster is also known as
congenital varicella syndrome, varicella embryopathy,
and chickenpox.
Incidence
First trimester varicella infections have been associated with an increased risk of spontaneous abortion.
Second trimester varicella infections have been associated with 2% risk of a congenital syndrome
characterized by limb hypoplasia, cutaneous scars, cataracts, microcephaly, and cortical atrophy.
Etiology
Herpesvirus is the etiologic agent

22. Diagnosis
The risk of fetal anomalies, however, is the greatest from 8 to 20 weeks’ gestation.
Sonographic signs of fetal disease include:
• fetal demise,
• growth restriction,
• musculoskeletal abnormalities (such as clubfeet and abnormal position of the
hands, caused by both necrosis and denervation of the affected tissue),
• limitation of limb extension due to cicatrices formation,
• cutaneous scars,
• limb hypoplasia,
• microphthalmia,
• polyhydramnios,
• hyperechogenic hepatic foci,
• cerebral anomalies (such as ventriculomegaly or atrophy and microcephaly),
disseminated foci of necrosis and microcalcifications, encephalitis, and
• echogenic bowel in the second trimester.
The placenta can show a multifocal chronic villitis with multinucleated giant cells.
Fetal infection can be demonstrated by detection of varicella zoster virus DNA by PCR
in fetal blood and amniotic fluid.
FIG. Varicella zoster infection. The
fetal face at autopsy (26 weeks).
Note the collapsed cranium, intact
skin (very little maceration),
disproportionate necrosis of the
ocular globes, and flattened midface.

23. TERATOGENS
1. Fetal Alcohol Syndrome/Fetal Alcohol Effects
2. Fetal Valproic Acid Syndrome
3. Fetal Warfarin Syndrome
4. Maternal Diabetes/Caudal Regression Syndrome

24. Fetal Alcohol Syndrome/Fetal Alcohol Effects
FAS is characterized by specific facial abnormalities and significant impairments in neurodevelopment and physical
growth.
Children exposed to alcohol (approximately 45 to 50 g of ethanol per day or equivalent) in utero suffer from
growth and mental retardation, physical abnormalities, and immune dysfunction.
Recommendations for clinicians regarding assessment of thresholds published by the National Institute on Alcohol
Abuse and Alcoholism recommend that any woman who reports drinking more than seven drinks per week or
more than three drinks on any given day be further assessed for risk of developing alcohol-related problems.
Synonyms
FAS is one of the fetal alcohol spectrum disorders.

25. Diagnosis
The findings include
• microcephaly,
• long round philtrum,
• small micrognathia,
• cleft palate,
• suppression of the cupid arch,
• microphthalmia,
• microcephaly,
• dysgenesis of the corpus callosum,
• malformed ears,
• atrial septal defect (ASD),
• ventricular septal defect (VSD), and
• growth restriction predominantly involving the limbs and occurring early without oligohydramnios.
Differential Diagnosis
Other conditions that involve growth restriction and microcephaly, such as congenital infections and
chromosomal anomalies, should be considered.

27. Fetal Valproic Acid Syndrome
Definition
• Fetal valproic acid exposure syndrome results from maternal valproate (an anticonvulsant) use during pregnancy
• characterized by CNS dysfunction, spina bifida, developmental delay, fetal growth restriction, and cardiac
anomalies.
Synonym
Depakote exposure is a synonym.
Incidence
Any epileptic pregnant mother has two to three times increased risk for congenital anomalies compared with the
general population.
If the exposure to valproic acid takes place between the 17th and 30th days after fertilization, the incidence of
neural tube defects approaches 1% to 2%.
In general, the teratogenic risks are higher with increasing doses of valproic acid, with a significantly higher rate of
malformations in doses up to 1000 mg/day.

28. Diagnosis
The findings include:
• cardiovascular abnormalities,
• hypotonia,
• spina bifida,
• hypospadias, and
• limb reduction.
The facial appearance can be characterized by
• oral cleft,
• small broad nose,
• small ears,
• flat philtrum,
• a long upper lip with shallow philtrum, and
• micrognathia/retrognathia.
Fetal growth restriction, microcephaly, generalized hypertrichosis sparing palms and soles, coarse face, gum hypertrophy,
clubfeet and clubhands, musculoskeletal abnormalities, genital abnormalities, and urogenital defects may also be present.
Heart defects have also been reported. Most frequently VSDs, aortic or pulmonary stenosis, and persistent ductus
arteriosus also occur.
Pulmonary hypoplasia is also reported.
Epilepsy and intellectual disability may develop after birth.

29. Associated Anomalies
Associated anomalies include omphalocele, inguinal hernia, duodenal atresia, and scoliosis. Hyperbilirubinemia,
hepatotoxicity, transient hyperglycinemia, afibrinogenemia, and fetal or neonatal distress may be found.

30. Fetal Warfarin Syndrome
Definition
Fetal warfarin syndrome is characterized by specific bone and cartilage abnormalities in the fetus,
including nasal hypoplasia, limb hypoplasia, and stippled epiphyses.
It is caused by fetal exposure to warfarin between weeks 6 and 12 of gestation.
Synonyms
Also been described as warfarin embryopathy and coumadin exposure.
Incidence
A wide range has been reported, but the best estimate is that less than 10% of exposed fetuses will
have embryopathy.
The teratogenic effect is dose-dependent, with greater safety if the dose is less than 5 mg/day.
Etiology
Warfarin freely crosses the placenta and is a known teratogen, with the highest risk between weeks
6 and 12 of gestation.

31. Diagnosis
Common sonographic findings include
• developmental abnormalities of bone and cartilage, specifically nasal and limb hypoplasia and stippled
epiphyses.
Associated Anomalies
CNS abnormalities have been more rarely reported and include microcephaly, optic atrophy, intellectual disability,
hypotonia, and spasticity.
Differential Diagnosis
Differential diagnosis includes other disorders affecting the bone and cartilage, specifically chondrodysplasia
punctata.

33. Maternal Diabetes/Caudal Regression Syndrome
Definition
Caudal regression syndrome is a rare congenital defect, characterized by the absence of the sacrum,
variable defects of portions of lumbar spine, and anomalies in other systems.
Synonyms
Caudal dysplasia sequence and sacral agenesis are other terms that have been used to describe caudal
regression syndrome.
Incidence
The incidence of caudal regression syndrome is 0.25 to 1 per 10,000 normal pregnancies.
This risk is 200 to 250 times higher in diabetic pregnancies.
Etiology
The cause is unknown, but caudal regression syndrome is associated with maternal diabetes in 16% of
the affected fetuses

34. Diagnosis
The sonographic findings are variable, and depend on the extent and severity of the defect. It ranges from
• complete absence of the sacrum associated with abnormalities of the lumbar spine and lower extremities (such
as clubfeet and contractions of the knees and hips) to abnormalities of the sacrum without associated defects.
The most typical findings are the
• absence of a few vertebrae,
• the shield-like appearance of the fused or approximated iliac wings, and
• decreased interspace between the femoral heads.
 A short crown-rump length and abnormal appearance of the yolk sac have been proposed as early sonographic
signs of caudal regression syndrome.
Differential Diagnosis
Sirenomelia is the main alternative diagnosis and was thought to be the most severe form of caudal regression
syndrome previously; it is now considered a separate entity.
Fusion of the lower extremities is generally seen in sirenomelia.

36. Central Nervous System
1. Aicardi Syndrome
2. Meckel Syndrome
3. Lissencephaly
4. Septo-optic Dysplasia
5. Tuberous Sclerosis
6. L1 Syndrome

37. Aicardi Syndrome
Definition
Aicardi syndrome is a neurodegenerative disorder first described in 1965, characterized by
• cerebral atrophy,
• intracerebral calcification of the basal ganglia,
• chronic cerebrospinal fluid lymphocytosis, and
• negative serologic investigations for common prenatal infections.
It was classically characterized by agenesis of the corpus callosum, chorioretinal lacunae, and infantile spasms.
Incidence
More than 100 cases have been reported. It is seen only in females and 47,XXY males.
Etiology
The disorder is thought to be caused by an X-linked dominant de novo gene mutation with lethality in 46,XY
males. The causative gene has not been identified.
Genetics
The genetics of Aicardi syndrome are unknown.

38. Diagnosis
The diagnosis is based on clinical features, including
• chorioretinal lacunae,
• brain MRI findings (corpus callosum dysgenesis, cerebral asymmetry, periventricular and intracortical
gray matter heterotopia, choroid plexus cysts, choroid plexus papillomas, ventriculomegaly), and
• skeletal findings (abnormal vertebrae and missing ribs).
Increased levels of interferon-α can been found in fetal blood and cerebrospinal fluid.
Associated Anomalies
Other features include characteristic facial features, GI difficulties, small hands, vascular malformations,
skin pigmentary lesions, and increased incidence of tumors.
Infrequently, there is associated cleft lip and palate.
Differential Diagnosis
Consider other causes of dysgenesis of the corpus callosum, including infectious causes.

39. FIG. Aicardi syndrome.
A, Ventriculomegaly; dilated lateral ventricle (arrow) is demonstrated in an axial image;
B, Dandy-Walker malformation with agenesis of the cerebellar vermis (arrow);
C, coronal magnetic resonance image of the fetal brain demonstrating agenesis of the corpus
callosum and an interhemispheric cyst.

40. Meckel Syndrome
Definition
Meckel syndrome (MKS) is a lethal ciliopathy characterized by
• occipital encephalocele,
• postaxial polydactyly of the hands and feet, and
• renal cystic dysplasia.
It is commonly associated with ductal plate malformations of the liver.
Synonyms
Dysencephalia splanchnocystica and Meckel-Gruber syndrome are synonyms for MKS.
Etiology
MKS is a ciliopathy, and the proteins encoded by the genes implicated in the disorder encode for proteins involved in
primary ciliary function.
Genetics
The disorder is genetically heterogeneous. The earliest implicated genes include MKS1 and MKS3.
Polydactyly is commonly found with MKS1 mutations and is rare with MKS3 mutations.
Milder CNS phenotypes are seen with MKS3 mutations.
Many of the same genes are also involved in Joubert syndrome

41. Diagnosis
The disorder can be detected prenatally as early as 11 to 14 weeks.
• Cystic dysplastic kidneys are seen in almost all cases of MKS (95-100%). The kidneys initially develop microscopic
cysts that destroy the parenchyma and enlarge the organ up to 10 or 20 times.
• Occipital cephalocele is present in 60% to 80%. Maternal serum or amniotic fluid alpha-fetoprotein (AFP) level
may be normal, as a membrane may cover the cephalocele.
• Other CNS findings include Dandy-Walker malformation and hydrocephalus.
• Postaxial polydactyly is present in 55% to 75% of fetuses.
• Other limb anomalies, such as bowing and shortening, may also be present.
• Liver histologic examination commonly demonstrates ductal plate malformations.
Oligohydramnios is caused by renal dysfunction and develops early in the second trimester when the kidneys
replace extracellular diffusion as the main source of amniotic fluid.
Differential Diagnosis
Conditions that can present with similar findings include trisomy 13 and 18, Joubert syndrome, Bardet-Biedl
syndrome, and Smith-Lemli- Opitz syndrome. Karyotype and molecular genetic testing can assist in clarifying the
diagnosis

44. Lissencephaly
Definition
Lissencephaly is a cerebral developmental disorder, with agyria of the brain, which may be accompanied by
pachygyria, minimal or no hydrocephalus, a wide cortical mantle, and characteristic dysmorphic features. The reduced
or absent brain gyri are caused by disturbed neuronal migration in the neocortex. Miller in 1963 and Dieker in 1969
provided the first descriptions.
Incidence
Incidence is uncertain, but estimates range from 11.7 to 40 cases per 1 million births.
Diagnosis
Sonographic diagnosis is difficult prior to the late second trimester, when the characteristic cerebral anomalies can be
noted. The progressive microcephaly and failure of development of both sulci and gyri (which normally become well
defined by 26 to 28 weeks) are suggestive of lissencephaly.
Specific lissencephaly-related syndromes are difficult to differentiate prenatally.
First-line genetic investigations involve chromosomal microarray, followed by next-generation sequencing multigene
panels or exome sequencing.

46. Tuberous Sclerosis
Definition
Tuberous sclerosis is characterized by
• abnormalities of the skin (facial angiofibromas, hypochromic patches),
• brain (cortical tubers, subependymal nodules and giant cell astrocytomas, seizures, intellectual
disability),
• kidneys (cysts, renal cell carcinomas, angiomyolipomas),
• heart (rhabdomyomas, arrhythmias), and
• lungs (lymphangioleiomyomatosis).
Synonyms
Tuberous sclerosis is also called Bourneville sclerosis and Bourneville disease.
Incidence
The incidence of tuberous sclerosis is up to 1 in 5800 births. Onset occurs in the first decade of life.
Etiology
Tuberous sclerosis is transmitted through autosomal-dominant inheritance. Two thirds of affected
individuals have a de novo mutation. The expression is highly variable.

47. Diagnosis
The diagnosis is usually suggested by the discovery of cardiac tumors, which resemble small uterine myomas
(round, usually well-delineated homogeneous masses).
Occasionally, the finding of a rhabdomyoma during routine second trimester ultrasound examination may
lead to the recognition that the mother is affected.
The rhabdomyomas may cause rhythm disruptions (Wolff-Parkinson-White syndrome, supraventricular
tachycardia, paroxysmal arrhythmias), as well as obstructions or regurgitation.
The presence of more than one rhabdomyoma is more likely to be associated with tuberous sclerosis than a
single identified lesion.
Renal angiofibromas have not been recognized prenatally, although this may simply be a matter of time.
Periventricular subependymal nodules may also be detected prenatally.
MRI can be performed to assess for the associated malformations

49. Genetics
Tuberous sclerosis is caused by defects or mutations in one of two genes,
TSC1 and TSC2.
TSC1 produces a protein called hamartin.
TSC2 produces a protein called tuberin.
Differential Diagnosis
The predominant prenatal finding is rhabdomyomas. Other cardiac
tumors, such as a fibroma, should also be considered.

50. MUSCULOSKELETAL SYSTEM
1. Skeletal Dysplasias
2. Other Lethal Skeletal Dysplasias
3. Vertebral Anomalies
4. Upper Extremity Anomalies
5. Lower Extremity Anomalies

51. SKELETAL DYSPLASIAS /OSTEOCHONDRODYSPLASIAS
a genetically heterogeneous group of over 350 distinct disorders.
They are traditionally classified in terms of which portions of the limbs are shortened:
• Rhizomelia: denotes shortening of the proximal limb, namely the humerus and femur
• Mesomelia :indicates shortening of the middle portion of the limb: the forearm or lower leg bone.
• Acromelia: is shortening of the hand and foot bones.
• Micromelia: technically means severe shortening of all portions of a limb, but the term is also used to indicate
shortening of a limb without a specific reference of the particular portion that is shortened
The SKELETAL DYSPLASIAS most commonly assessed by ultrasound are:
1. Thanatophoric dysplasia
2. Osteogenesis imperfecta
3. Achondroplasia
4. Achondrogenesis
5. Campomelic dysplasia
6. Atelosteogenesis

52. 1. Thanatophoric Dysplasia
 TD is the most common lethal skeletal dysplasia
Characterized by :
• severe rhizomelia
• small thorax
• normal trunk length
• normal bone mineralization
• no fractures
• thickened redundant skin
• platyspondyly (flattened vertebral bodies)
 TD is divided into two subtypes:
1. Type 1: TD1 is the more common form. The femurs have a “telephone receiver” shape, and frontal bossing
and midface hypoplasia are present. Cloverleaf skull is not seen.
The hands and feet are normal, but the fingers are short.
1. Type II: TD2 is the less common form. Femurs are straight with flared metaphyses, and a cloverleaf skull is
present (due to craniosynostosis of the lambdoid and coronal sutures).

53. Diagnosis
• Prenatal findings include severe rhizomelia (seen as early as 12-14 weeks) and hypoplastic thorax
• Craniofacial dysmorphisms include macrocephaly, frontal bossing, midface hypoplasia, and cloverleaf skull.
• brachydactyly
• platyspondyly
• hypotonia
• redundant skinfolds
• polymicrogyria deep
• transverse temporal sulci
• temporal lobe enlargement.
• Polyhydramnios
FIG 1. FIG 2
FIG 3
FIG 3
FIG 3

54. 2. Osteogenesis Imperfecta
Heterogeneous group of genetic disorders that affect the type I collagen.
It is characterized by severe bone fragility, blue sclera and prenatal growth deficiency.
The four types are described as follows:
1. Type I: classic nondeforming OI with blue sclerae. Deformities are not seen prenatally.
2. Type II: perinatal lethal OI. This is the most severe form and can be seen prenatally.
3. Type III: progressively deforming OI. Some features can be seen prenatally.
4. Type IV: common variable OI with normal sclerae. Deformities are not generally seen prenatally.
Etiology
COL1A1 and COL1A2 encode for type I collagen (found in skin, ligaments, tendons, demineralized bone,
and dentine).
Defective production of type I collagen leads to decreased bone mineralization and bone fragility.

55. Diagnosis
Type II is the most severe form and affected individuals usually die in utero or shortly after birth
from severe fractures and pulmonary hypoplasia.
Key prenatal findings include
• severe micromelia (femur length more than 3 standard deviations [SD] below the mean),
• small thorax,
• normal head circumference,
• short trunk,
• decreased bone mineralization (including decreased ossification of the skull), and
• multiple bone fractures. Multiple fractures may lead the long bones to appear angulated.
Both cortices of a bone are often seen.
Some findings can be seen as early as 13 to 15 weeks’ gestation.

56. Osteogenesis Imperfecta type 1

57. Osteogenesis Imperfecta type 2

60. 3. Achondrogenesis
Definition
Achondrogenesis is a heterogeneous group of lethal skeletal dysplasias characterized by
• severe micromelia,
• small thorax,
• short trunk,
• decreased bone mineralization (particularly of the vertebrae, sacrum, and pubic bones), and
• occasional fractures.
The most common types are described here:
1. Type 1: includes type 1A and type 1B. Deficient bone mineralization also affects the calvarium.
2. Type 2: similar to type 1, with less severe mineralization deficits.

61. Diagnosis:
AO should be suspected in cases with very flattened facies with micrognathia and hypoplastic appendicular
bones that are frequently absent or poorly formed, with hypoplastic distal ends, and polyhydramnios
Subtypes of achondrogenesis may be identified by specific features, as follows:
1. Type IA: Rib fractures and poor ossification of the skull
2. Type IB: Absence of rib fractures, poor ossification of the spine, and sometimes umbilical or inguinal hernia
3. Type II: Absence of rib fractures, normal ossification of the skull, and some ossification of the spine In type II,
there are also metaphyseal spikes at the ends of the bones.

62. 4. Achondroplasia
Achondroplasia is a relatively common non-lethal skeletal dysplasia characterized by
• rhizomelia,
• macrocephaly, and
• characteristic facial features (frontal bossing and flat midface)
Etiology
The FGFR3 mutation, p.Gly380Arg,seen in achondroplasia leads to constitutive activation of FGFR3.
This results in inhibition of chondrocyte proliferation and differentiation and negatively regulates bone growth

63. Diagnosis
Prenatally, a shortened femur in comparison to the head circumference can been seen in the second trimester;
Femur length is often at the 3rd percentile or less by 25 weeks’ gestation
Fetuses with normal interval growth in femoral length during the second trimester are expected to be unaffected.
The craniofacial features, including macrocephaly, frontal bossing, and flat midface, can also be seen.
Occasionally more subtle anomalies, such as the trident hand (an increased space between the third and fourth digit) or
the lack of widening of the lumbar canal, can also be identified.

65. 5. Campomelic Dysplasia
Campomelic dysplasia (CD) is a skeletal dysplasia characterized by
• abnormal facies,
• multiple congenital anomalies,
• a typical pattern of skeletal abnormalities, and
• frequent male-to-female sex reversal.
CD is due to heterozygosity for mutations in the SOX9 gene that is involved with both SRY function and
endochondral ossification

66. Diagnosis
The most striking feature is anterior bowing of the long bones,
particularly the femur and tibia.
Other features seen on ultrasound imaging include
• 11 pairs of ribs,
• a bell-shaped narrow chest,
• relatively large head,
• Pierre Robin sequence with cleft palate,
• flat face with high forehead,
• laryngotracheomalacia,
• cervical spine anomalies,
• scoliosis,
• scapular hypoplasia,
• ambiguous genitalia (or normal female genitalia in a 46,XY
individual),
• dislocated hips,
• clubfeet, and
• hydrocephalus.
Cardiac and renal anomalies have also been reported.
Polyhydramnios may be present.

67. (6A.) Klippel-Feil Syndrome
Klippel-Feil syndrome (KFS) is characterized by a classic triad of
1. short neck,
2. low posterior hairline, and
3. fusion of cervical vertebrae
KFS may be classified by degree and location of vertebral fusion.
1. Type I is a fusion of cervical and upper thoracic vertebrae with synostosis
2. Type II is isolated fusion of the cervical spine
3. Type III shows fusion of cervical vertebrae associated with lower thoracic
or upper lumbar fusion.
VERTEBRAL ANOMALIES

68. Diagnosis
The short neck may be associated with opisthotonos (retroflexion of the head), and disorganization of the cervical
vertebrae is potentially recognizable.
Other associated anomalies include
• ocular malformations,
• cleft lip and palate,
• oligodontia,
• craniofacial asymmetry,
• maxillary constriction and velopharyngeal insufficiency,
• persistent trigeminal artery,
• congenital heart defects, and
• urogenital anomalies.
Some cases occurring with situs inversus totalis have been reported.

69. (7A.) Holt-Oram Syndrome
Holt-Oram syndrome (HOS) is characterized by congenital heart disease and anomalies of the upper limbs
(specifically anomalies of the carpal, radial, or thenar bones).
It is the most common heart-hand syndrome.
Diagnosis
Congenital heart defects are present in 75% of individuals with HOS.
The cardiac lesions include ASDs (30-60%) and VSDs, patent ductus arteriosus, endocardial cushion defect,
hypoplasia of the left ventricle, and conduction disturbances (atrioventricular block that usually presents as first-
degree heart block but can progress to complete heart block ± atrial fibrillation).
Radial ray aplasia can vary from a difficult to diagnose triphalangeal thumb to a more obvious clubhand to
absence of the thumb.
UPPER EXTREMITY ANOMALIES

71. To be continued……
THANKYOU !