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FGFR3 Disorders: Thanatophoric Dysplasia, Achondroplasia, and Hypochondroplasia

Introduction Fibroblast growth factor receptor 3 (FGFR3) disorders compromise of a spectrum of disorders that include thanatophoric dysplasia, achondroplasia, and hypochondroplasia, among other rare disorders such as severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and craniosyntoses syndromes. They are all inherited as autosomal dominant disorders due to heterozygosity for mutations in FGFR3 . Achondroplasia is the most frequent cause of nonlethal dwarfism and is…

DTDST Dysplasia (Including AOII and Achondrogenesis IB)

Introduction Diastrophic dysplasia (DTD) is an autosomal, recessively inherited skeletal dysplasia characterized by short limbs, normal-sized skull, cleft palate in one-third of patients, characteristic swelling of the pinnae cartilage, contractures of the large joints with deformities, spinal abnormalities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis), and a distinct brachydactyly associated with the characteristic “hitchhiker” thumbs. Newborns with DTD have an increased risk of mortality in the neonatal…

Chondrodysplasia Punctata

Introduction Chondrodysplasia punctata refers to a group of skeletal dysplasias that are characterized primarily by punctate calcifications in cartilage (calcific stippling). These disorders are characterized by short-limb dwarfism, spinal abnormalities, facial dysmorphisms, joint contractures, skin lesions, and occasionally cardiac malformations. There are multiple types of chondrodysplasia punctata, and there is extensive locus and allelic heterogeneity. Disorder Definition The term chondrodysplasia punctata describes a group of osteochondrodysplasias…

Campomelic Dysplasia

Introduction 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. Newborns with CD often die as a result of respiratory insufficiency and congenital anomalies. A small subset of individuals with clinical features of CD lack characteristic long bone bowing and are classified as having acampomelic campomelic dysplasia. CD results from…

Atelosteogenesis Disorders

Introduction Atelosteogenesis (AO) refers to a group of lethal short-limb skeletal dysplasias characterized by an abnormal, characteristic facies and hypoplastic or dysplastic tubular bones. Specific radiographic abnormalities, distinct histopathology, and differing inheritance patterns distinguish the three well-recognized types of AO. All three forms have abnormal facies and short limbs, but associated findings help distinguish them from each other; for example, synpolydactyly, omphalocele, and frontal encephalocele are…

Nuchal Translucency

Introduction In 1866, Down first reported an accumulation of excessive skin in individuals with trisomy 21. In the early to mid-1990s, ultrasound (US) evaluation in the first trimester revealed an accumulation of subcutaneous fluid behind the fetal neck that could explain the apparent excess skin; this finding became known as nuchal translucency (NT). An increase in NT is now recognized to be an early presenting feature…

Pregnancy of Unknown Location, Early Pregnancy Loss, Ectopic Pregnancy, and Cesarean Scar Pregnancy

Introduction Pregnancy is an inefficient process. A large proportion of early pregnancies end in miscarriage or early pregnancy failure. Ectopic pregnancies (EP), those located outside of the proper uterine location, cause significant maternal morbidity and mortality. It is the role of the clinician to establish that the pregnancy is properly situated within the uterus and viable. This chapter will review the utility of ultrasound (US) in…

Ventriculomegaly

Introduction Ventriculomegaly (VM) is a nonspecific term, describing dilatation of the lateral cerebral ventricles, usually defined as greater than 10 mm at the level of the atria. VM is the most frequent abnormal central nervous system (CNS) finding detected with prenatal imaging techniques. It is not a disease, but rather a sign that represents a common endpoint of various pathologic processes with different outcomes and prognosis; it…

Vascular Cerebral Anomalies

Introduction Cerebral vascular malformations are rare but potentially disastrous abnormalities. Aneurysm of the vein of Galen is the most common abnormality described in prenatal series. Other types of intracranial vascular malformations are diagnosed prenatally only rarely. In the neonatal period, the clinical features include cyanosis, systolic murmur secondary to hyperdynamic circulation, cardiomegaly, and increased intracranial pressure. Before the availability of ultrasound (US) diagnosis, most cerebral vascular…

Neural Tube Defects

Introduction Neural tube defects (NTD) are the consequence of a failure in the closure of the neural tube, and differ depending on their localization and extent. The term “neural tube defects” includes defects of the cranial vault, including the spectrum of acrania, exencephaly, and anencephaly, and encephaloceles, spinal defects (“spina bifida” or myelomeningocele), and combined cranial and spinal defects such as craniorachischisis. These defects, as well…

Intracranial Hemorrhage, Cysts, Tumors, and Destructive Lesions

Introduction Destructive cerebral lesions are not embryonic malformations, but rather the result of an insult to a normally developed fetal brain. The most common causes are hemorrhage, hypoxia-ischemia, and infections, but the pathophysiology is unclear in many cases. The prognosis is usually poor. This chapter describes the main features of fetal intracranial destructive lesions, including intracranial hemorrhages, porencephaly, hydranencephaly, and schizencephaly. Other intracranial lesions that develop…

Holoprosencephaly

Introduction Holoprosencephaly (HPE) has been known since antiquity through the figure of the cyclopean shepherd Polyphemos in Homer's Odyssey (circa 800 bc ). Until the 17th century, a cyclopic newborn, whether it was a human or an animal, was associated with mystic and fabulous narrations. In the 18th century, HPE and other anomalies were recognized as congenital conditions, and cases of HPE were collected and described…

Walker-Warburg Syndrome

Introduction Walker-Warburg syndrome (WWS) is a rare, lethal congenital diffuse neurodysplasia, characterized by variable ocular and cerebral abnormalities. Cerebral findings include ventriculomegaly, encephalocele, and Dandy-Walker malformation. Ocular findings are varied, may occur in the posterior or anterior segments of the eye, or both, and include microphthalmia, congenital cataracts, corneal opacities, nonreactive pupils, iris synechiae, optic disk colobomas, and retinal dysplasia or detachment. Disease Definition The principal…

Cerebellar Anomalies

Introduction The fetal cerebellum develops throughout pregnancy and may be visualized starting from the first trimester. By the seventh week of gestation, the rhombencephalic vesicle, the precursor of the fourth ventricle and cisterna magna, is the most prominent structure of the brain. By the eighth week, the cerebellar hemispheres may be seen lateral to the fourth ventricle; the choroid plexus of the fourth ventricle is also…

Cortical Development and Disorders

Introduction Cortical neuronal cell development starts at about 7 weeks' gestation from stem cells in the germinal matrix that line the ventricles. The stem cells proliferate and differentiate into glial cells and neurons. The glial cells migrate radially to the brain surface and create a scaffold for the neurons to follow to the outer cortex, where the neurons organize connections and commissures. Other neurons derived from…

Septooptic Dysplasia

Introduction Septooptic dysplasia (SOD), also known as de Morsier syndrome, is a rare heterogeneous disorder. It is characterized by optic nerve hypoplasia and midline forebrain abnormalities, such as agenesis of the corpus callosum, absence of the cavum septi pellucidi, and pituitary hypoplasia with consequent panhypopituitarism. It has been proposed that the terms SOD and de Morsier syndrome should be abandoned, as they are not independent entities.…

Corpus Callosum and Septum Pellucidum Anomalies

Introduction Anomalies of the corpus callosum and septum pellucidum are disorders of prosencephalic midline development. Midline prosencephalic development peaks at 7 to 12 weeks' gestation and includes the formation of the chiasmatic, commissural, and hypothalamic plates, enabling formation of the corpus callosum (12 to 20 weeks) and septum pellucidum. Corpus callosum and septum pellucidum anomalies are often associated with other brain abnormalities. Corpus Callosum Anomalies Definition…

Choroid Plexus Anomalies: Cysts and Papillomas

Introduction The choroid plexus is a vascular convolute, consisting of epithelial cells (a type of microglia), fenestrated blood vessels, and stroma, which lie in the ventricular system of the brain. It is the main source of cerebrospinal fluid (CSF) and actively regulates the constituents in CSF. The choroid plexus epithelial cells and the tanycytes, special ependymal cells located in the floor of the third ventricle, constitute…

Fetal Spleen

Introduction The fetal spleen is an important center of hematopoiesis until the late fetal period. In postnatal life, the function of the spleen is mainly as an immune organ, with lymphocyte and monocyte production continuing throughout adult life. During fetal development, the spleen appears between the fifth and eighth gestational weeks as an aggregation of reticular mesenchymal cells in the dorsal epigastrium of the stomach. The…

Sacrococcygeal Teratoma and Fetus in Fetu

Introduction Sacrococcygeal teratoma (SCT) is the most common tumor in newborns. Fetal SCT diagnosed in utero is associated with a 50% risk of preterm delivery, a mortality rate of 15% to 35%, and a morbidity rate of 12% to 68%. Perinatal mortality and morbidity are high because of high-output cardiac failure, fetal hydrops, preterm delivery, anemia, dystocia, and tumor rupture. The intrapelvic and intraabdominal extent of…