Arthrogryposis

This chapter reviews the incidence, risk factors, genetics, recurrence risk, and epidemiology of arthrogryposis. The most common and clinically recognizable type among the congenital contractures is amyoplasia, and treatment options are improving the quality of life for these patients. The distal arthrogryposes are mostly autosomal dominant and caused by an increasing number of genes including variants in PIEZ02 and MYH3 among several others. The lethal contracture syndromes have an expanding number of causes many of which are autosomal recessive. The majority of these conditions are recognized on US. In viable syndromes the early and intensive use of physical therapy is critical and can result in significant joint mobilization. The clinical case presentation features an infant with lethal multiple pterygia syndrome.

Twins

This chapter reviews the incidence, risk factors, and epidemiology of disorders associated with twinning. The timing of twinning and the types of twins are reviewed. The fetal and perinatal complications of twinning including twin to twin transfusion and its treatment are discussed, as well as the possible consequences of death of a monozygotic co-twin. These include severe disruptive brain abnormalities, and other vascular disruptive defects. The birth defects more common in twins are enumerated and specific patterns of birth defects such as hemifacial macrosomia and VACTERL are discussed. A clinical case presentation features monozygotic twins with twin-to-twin transfusion syndrome and congenital heart disease.

Overgrowth

This chapter reviews information on disorders that cause large birth weight, macrosomia, and/or segmental overgrowth. The most common of these conditions is seen in infants of diabetic mothers. Abnormal dosage of growth regulating genes make chromosomal microarray abnormalities a relatively common cause of overgrowth. Particularly notable is the distinctive Pallister Killian syndrome (12p tetrasomy). Other common overgrowth syndromes include Beckwith-Wiedemann syndrome, Sotos, Malan, and Weaver syndromes. The RASopathy syndromes including Noonan syndrome* and Costello syndrome are also often large at birth. Segmental overgrowth syndromes including Proteus and Klippel Trenaunay as well as PIK3CA related overgrowth (PROS) are discussed as well as their somatic mosaic origin in affected tissues. Clinical guidelines for evaluation and surveillance are outlined. The clinical case presentation features an infant with Sotos syndrome.

Skeletal Dysplasias

This chapter discusses a general approach to diagnosing and preparing for the birth of an infant with a skeletal dysplasia. The discussion on the prenatal evaluation includes the importance of the gestational age at which US skeletal changes are apparent, the assessment of body proportions, as well as nd bone density and morphology. The ratio of long bone to chest circumference can guide a determination of viability or lethality. Rapid targeted prenatal exome testing may aid decision making. Formation of a prenatal birth plan is suggested. Recommendations on evaluating an infant with a skeletal dysplasia after birth include how and what to measure, what radiographs to order and how to pick the most relevant genetic testing approach. The importance of genetic follow up is stressed. The clinical case presentation features an infant with hypochondrogenesis.

Syndactyly

This chapter reviews background information about the incidence, risk factors, genetics, recurrence risk, epidemiology, and some subtypes of syndactyly. Various unilateral and bilateral patterns of syndactyly, including common autosomal dominant isolated cutaneous syndactyly and rarer presentations of complex syndactyly with bony fusion, are reviewed. Associated malformations, such as small size, microcephaly, craniosynostois, facial dysmorphism, and other limb anomalies, that are often seen with syndactyly are presented. The discussion on the differential diagnosis of syndactyly summarizes its common causes, including teratogenic agents, chromosome anomalies, and Mendelian multiple congenital anomaly syndromes, and it gives recommendations for evaluation and management. A clinical case presentation features an infant with oculo-dento-digital dysplasia.

Upper Extremity Anomalies

This chapter reviews background information about the incidence, epidemiology, genetics, and other anomalies associated with common congenital anomalies of the upper extremity. The discussion reviews the differential diagnosis of transverse, longitudinal (amelia, radial, ulnar), intercalary (phocomelia), and central (split hand/foot) defects of the radius and ulna and combined upper and lower extremity defects. The chapter summarizes common causes of upper extremity anomalies, including amniotic band disruption sequence, teratogenic agents (misoprostol, thalidomide, valproic acid), vascular disruption, chromosome anomalies, and Mendelian congenital malformation syndromes, and it gives recommendations for evaluation and management. A clinical case presentation features an infant with Holt–Oram syndrome.

Gastroschisis

This chapter reviews the incidence, risk factors, genetics, recurrence risk, epidemiology, and distinctive anatomy of gastroschisis. This abnormality is much more common in the offspring of young mothers and the overall incidence continues to rise worldwide. Other risk factors include short intrapregnancy intervals, smoking and several medications such as aspirin and ibuprophen. Associated abnormalities most frequently include intestinal atresias and strictures although other vascular disruptive defects, particularly the amyoplasia form of arthrogryposis, are seen in 3-10%. Distinquishing this defect from omphalocele is usually not difficult although a ruptured omphalocele may cause confusion. Ruling out limb-body wall disruption is important as the prognosis is vastly different. The clinical case presentation features an infant with amyoplasia and gastroschisis.

Diaphragmatic Hernia

This chapter reviews background information about the incidence, risk factors, genetics, family history, recurrence risk, and epidemiology of isolated and syndromic diaphragmatic hernia. The chapter reviews the typical multifactorial inheritance pattern of isolated sporadic diaphragmatic hernia and its low recurrence risk, which is distinct from more complex single gene disorders. The discussion on the differential diagnosis of diaphragmatic hernia summarizes other intrathoracic disorders that can give a similar radiographic appearance. The common genetic causes of diaphragmatic hernia are discussed including chromosome anomalies (aneuploidy, mosaic tetrasomy 12p, recurrent copy number variants), and Mendelian disorders that include malformations in other organ systems and overgrowth conditions. The chapter gives recommendations for evaluation and management. A clinical case presentation features a large for gestational age infant with diaphragmatic hernia and bitemporal alopecia caused by Pallister–Killian syndrome.

Cleft Palate

This chapter reviews background information about the incidence, risk factors, family history, sex ratio, genetics, recurrence risk, and epidemiology of isolated and syndromic cleft palate. Microforms of cleft palate including bifid uvula, submucous cleft palate, and nasal regurgitation are described. The discussion on the differential diagnosis of cleft palate summarizes its common causes, including teratogenic agents (alcohol, maternal diabetes, valproic acid), chromosome anomalies, and Mendelian disorders associated with malformations in other organ systems. The chapter provides recommendations for evaluation and management. A clinical case presentation features an infant with micrognathia, a cleft of the soft palate, and a retropositioned tongue and respiratory distress due to Pierre–Robin sequence.

Ear Anomalies

This chapter reviews background information about the incidence, risk factors, genetics, recurrence risk, family history and epidemiology of isolated and syndromic ear anomalies. The discussion on the differential diagnosis of ear anomalies summarizes its common causes, including teratogenic agents (isotretinoin, maternal diabetes, mycophenylate), chromosome anomalies (aneuploidy, 22q11 deletion), common sporadic multiple congenital anomaly syndromes (Hemifacial microsomia/Goldenhar), and Mendelian disorders that are primarily craniofacial (Treacher-Collins and other mandibulofacial dysostoses) and others that include malformations in other organ systems (CHARGE). The chapter gives recommendations for evaluation and management. A clinical case presentation features a child with mycophenylate embryopathy, who had been incorrectly diagnosed with Treacher Collins syndrome.