| Genetic syndrome |
Inheritance |
Birth prevalence |
Prognosis and common sonographically detectable abnormalities |
| Achondrogenesis |
AR |
1 in 40,000 |
Lethal skeletal dysplasia. Severe limb shortening, narrow thorax,
hypomineralization of the vertebral bodies. Mineralisation of the
skull normal in type II and poor in type I. |
| Achondroplasia* |
AD |
1 in 26,000 |
Intelligence and life expectancy are normal. Short limbs, macrocephaly,
depressed nasal bridge, lumbar lordosis and short limbs, usually
after 22 weeks |
| Adrenal hyperplasia* |
AR |
1 in 5,000 |
Deficiency in one of the enzymes of cortisol biosynthesis, resulting
in overproduction of cortisol precursors and androgens. Increased
NT, ambiquous genitalia in females. |
| Asphyxiating thoracic dystrophy |
AR |
1 in 70,000 |
Variable prognosis from neonatal death to normal survival. Narrow
chest and rhizomelic limb shortening, which may not become apparent
until after 22 weeks. |
| Beckwith–Wiedemann syndrome |
Sporadic |
1 in 14,000 |
In some cases, there is mental handicap, which is thought to
be secondary to inadequately treated hypoglycemia. About 5% develop
tumors during childhood, most commonly nephroblastoma and hepatoblastoma.
Prenatal sonographic features include macrosomia and exomphalos. |
| Blackfan-Diamond anemia |
AD, AR |
1 in 200,000 |
Congenital hypoplastic anemia requiring treatment with steroids
and repeated blood transfusions. The risk of hematologic malignancies,
mainly acute leukemia, is increased. Thumb defects, hypertelorism,
cardiac and urogenital anomalies. |
| Blomstrand osteochondrodysplasia |
AR |
Rare |
Lethal skeletal dysplasia. Severe limb shortening, narrow thorax,
increased bone density. |
| Brachmann-Cornelia de Lange syndrome |
AD |
1 in 160,000 |
Mental handicap. Fetal growth restriction, short limbs, heart
defects, diaphragmatic hernia. |
| Campomelic dysplasia |
AR |
1 in 200,000 |
Lethal skeletal dysplasia. Short and bowed lower limbs with
narrow thorax. |
| CHARGE association |
Sporadic |
Rare |
Acronym for Coloboma of the eye, Heart anomaly, choanal Atresia,
growth and mental Retardation, Gonadal hypoplasia and Ear abnormalities
and/or deafness. There may not be any antenatal sonographic findings. |
| Cleidocranial dysplasia |
AD |
Rare |
Normal life expectancy. Hypoplastic clavicles and nasal bone. |
| Di George syndrome |
Sporadic |
1 in 4,000 |
Results from de novo 22q11 deletion in 90% of cases. Characterized
by neonatal hypocalcemia, due to hypoplasia of the parathyroid glands,
and susceptibility to infection due to hypoplasia or aplasia of
the thymus gland. A variety of cardiac malformations are seen, including
tetralogy of Fallot, interrupted aortic arch, truncus arteriosus,
right aortic arch and aberrant right subclavian artery. Short stature
and mild to moderate learning difficulties are common. |
| Dyserythropoietic anemia |
AD, AR |
Rare |
Congenital, usually mild anemia. In some cases there is severe
anemia presenting with fetal hydrops. |
| Ectrodactyly-ectodermal dysplasia-cleft palate syndrome |
AD |
Rare |
Wide variability in phenotypic expression. Split hand and foot,
cleft lip and/or palate. |
| Erythropoietic porphyria (Gunther’s disease) |
AR |
Rare |
Usually presents during childhood with severe cutaneous photosensitivity
with progressive bullous lesions, leading to infection, bone resorption,
cutaneous deformity and chronic hemolytic anemia. Severe cases present
with fetal hydrops. |
| Fanconi anemia |
AR |
1 in 22,000 |
Congenital aplastic anemia characterised by pancytopenia and
spontaneous chromosome instability. The phenotype and age of onset
are variable. There may be no prenatal sonographically detectable
abnormalities. |
| Fetal akinesia deformation sequence |
AR, sporadic |
Rare |
Heterogeneous group of conditions resulting in multiple joint
contractures, frequently associated with fetal myopathy, neuropathy
or an underlying connective tissue abnormality. Severe cases present
with arthrogryposis and increased NT in the first trimester. |
| Fowler syndrome |
AR |
Rare |
Proliferative vasculopathy of the central nervous system that
leads to disruption, disorganisation and hemorrhagic necrosis of
the developing brain. Prenatal features include hydranencephaly
and arthrogryposis. |
| Fryn syndrome |
AR |
1 in 15,000 |
Usually lethal. Diaphragmatic hernia, digital defects, short
webbed neck. |
| GM1-Gangliosidosis* |
AR |
Rare |
Progressive neurological deterioration, resulting in early and
severe retardation of both motor and mental development. Death occurs
within the first 10 years of life from chest infections. Prenatal
sonographic findings include visceromegaly and generalized edema. |
| Hydrolethalus syndrome |
AR |
1 in 20,000 |
Lethal condition characterized by hydrocephalus, absent corpus
callosum, facial cleft, micrognathia, polydactyly, talipes and cardiac
septal defects. |
| Hypochondroplasia |
AD |
1 in 26,000 |
Resembles achondroplasia and is characterised by short-limb
dwarfism manifesting during childhood. Prenatally there may be short
limbs and macrocephaly. |
| Hypophosphatasia |
AR |
1 in 100,000 |
Subdivided into perinatal, infantile, childhood and adult forms,
according to the age of onset of symptoms. In the perinatal type
there is hypomineralization of the skull and spine, short limbs
and narrow thorax. |
| Infantile polycystic kidney disease |
AR |
1 in 10,000 |
Subdivided into perinatal, neonatal, infantile, and juvenile,
depending on the severity of the disease and age of presentation.
Prenatal sonographic features include large, echogenic kidneys and
oligohydramnios. |
| Jarcho–Levin syndrome |
AR |
1 in 500,000 |
Heterogeneous disorder characterized by scoliosis and disorganization
of the spine. There are two types. In spondylothoracic dysplasia
there is a narrow thorax and lethal respiratory insufficiency in
infancy. Spondylocostal dysplasia is associated with survival to
adult life but with some degree of physical disability. |
| Joubert syndrome |
AR |
Rare |
Profound mental retardation and developmental delay. Death usually
occurs in the first 5 years of life. Partial or complete absence
of the cerebellar vermis |
| Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency* |
AR |
Rare |
Lethal disorder. Muscular hypotonia, cardiomyopathy, hydrops |
| Lymphedema |
AD |
Rare |
Hypoplastic/aplastic lymphatic vessels, usually affecting the
lower limbs. Three clinical subtypes, congenital (Milroy disease,
present at birth), praecox (pubertal onset) and tarda (midlife onset),
with congenital lymphedema being the rarest and most severe of the
three. There may be no prenatal sonographic findings. |
| Meckel–Gruber syndrome |
AR |
1 in 10,000 |
Lethal. Typical features are encephalocele, bilateral polycystic
kidneys, polydactyly. |
| Mucopolysaccharidosis type VII* |
AR |
Rare |
Mental retardation, short stature, macrocephaly, hearing loss,
corneal opacities and recurrent lower respiratory tract infection. |
| Myotonic dystrophy* |
AD |
1 in 25,000 |
The genetic defect is an amplified trinucleotide repeat in a
protein kinase gene on chromosome 19. Age of onset and severity
of disease vary with the number of repeats. The mutation can worsen
progressively in successive generations and the severe congenital
form occurs almost exclusively in the offspring of affected women.
Prenatal sonographic signs may be decreased fetal movements and
polyhydramnios in the third trimester. |
| Nance–Sweeney syndrome |
AR |
Rare |
Intelligence and life expectancy are normal. Short limbs, vertebral
abnormalities. |
| Nephritic syndrome* |
AR |
1 in 8,000 in Finland |
Renal failure requiring transplantation within the first 4 years
of life. Prenatally may present with transient hydrops |
| Noonan syndrome |
AD |
1 in 2,000 |
Life expectancy is probably normal in those without severe heart
disease. Mild mental retardation is present in about one-third of
cases . |
| |
|
|
The majority of cases are diagnosed Postnatally. Prenatal sonographic
findings include skin edema, hydrothorax, polyhydramnios, and cardiac
defects, such as pulmonic stenosis and hypertrophic cardiomyopathy
but these may become apparent only in the third trimester. |
| Osteogenesis imperfecta type II* |
AR |
1 in 60,000 |
Lethal skeletal dysplasia. Short limbs and ribs with multiple
fractures, hypomineralization of the skull. |
| Perlman syndrome |
AR |
Rare |
Similar to Beckwith–Wiedemann syndrome. Fetal and neonatal mortality
is more than 60% and, in survivors, there is a high incidence of
neurodevelopmental delay. Sonographic features include progressive
macrosomia and enlarged kidneys. |
| Roberts syndrome |
AR |
Rare |
Associated with the cytogenetic finding of premature centromere
separation and puffing. Characterized by symmetrical limb defects
of variable severity (tetraphocomelia), facial cleft, microcephaly
and growth restriction. |
| Robinow syndrome |
AR |
Rare |
Skeletal defect with short forearms, frontal bossing, hypertelorism,
and vertebral anomalies |
| Short-rib polydactyly syndrome |
AR |
Rare |
Lethal skeletal dysplasia. There are four types. Type I (Saldino–Noonan)
has narrow metaphyses; type II (Majewski) has facial cleft and disproportionally
shortened tibiae; type III (Naumoff) has wide metaphyses with spurs;
type IV (Beemer–Langer) is characterized by median cleft lip, extremely
short ribs and pro-tuberant abdomen with umbilical hernia. Prenatal
sonographic findings include short limbs, narrow thorax and polydactyly |
| Smith–Lemli–Opitz syndrome* |
AR |
1 in 20,000 |
High perinatal and infant mortality and severe mental retardation
Prenatal sonographic features include polydactyly, cardiac defects,
ambiguous or female external genitalia in the male. |
| Spinal muscular atrophy type 1* |
AR |
1 in 7,000 |
Progressive muscle weakness leading to death before two years
of age because of respiratory failure. Decreased fetal movements
are commonly reported and symptoms usually start at birth or up
to six months of age. |
| Stickler syndrome |
AD |
1 in 10,000 |
Progressive myopia beginning in the first decade of life, resulting
in retinal detachment and blindness, sensorineural hearing loss,
marfanoid habitus with normal height, premature degenerative changes
in various joints. There may be no prenatal sonographic findings
but in some cases there is a facial cleft, or micrognathia. |
| Thalassaemia-α* |
AR |
Common in Mediterranean and Asian populations |
The alpha locus determines a polypeptide chain, the α-chain,
which is present in adult hemoglobin (α2/ß2), fetal hemoglobin
(α2/α2) and embryonic hemoglobin (α2/α2).
Normally there are four alpha gene copies. Absence of all four α-genes
results in homozygous α-thalassemia, which presents with hydrops
fetalis, usually in the second trimester. |
| Thanatophoric dysplasia* |
Sporadic |
1 in 10,000 |
Lethal skeletal dysplasia. Severe limb shortening, narrow thorax,
enlarged head with prominent forehead. |
| Treacher Collins syndrome |
AD |
1 in 50,000 |
Normal life expectancy. Micrognathia, deformities of the ears |
| Trigonocephaly ‘C’ syndrome |
AR |
1 in 15,000 |
About half of the affected individuals die in infancy while
survivors are severely mentally handicapped with progressive microcephaly.Trigonocephaly,
short nose, prominent maxilla |
| VACTER association |
Sporadic, AR |
1 in 6,000 |
Acronym for Vertebral abnormalities, Anal atresia, Cardiac defects,
Tracheo-Esophageal fistula with esophageal atresia, Radial and Renal
defects. Prognosis depends on the particular combination and severity
of the abnormalities present. Mental function is usually normal. |
| Vitamin D resistent rickets |
AR |
Rare |
None |
| Zellweger syndrome* |
AR |
1 in 25,000 |
Death occurs in the first two years of life, most commonly due
to chest infections and liver failure. Prenatal features include
hypertelorism, brain and cardiac defects, hepatomegaly, growth restriction |