Dysmorphology is the recognition of the pattern of congenital malformations (often multiple congenital malformations) and dysmorphic features that characterize a particular syndrome. Syndromes are collections of abnormalities, including malformations, deformations, dysmorphic features, and abnormal behaviors that have a unifying, identifiable etiology. This etiology may be the presence of a mutation in a single gene, as is the case in Rett syndrome, a disorder that is caused by a mutation in the MECP2 gene on Xq28; by the deletion or duplication of chromosomal material, as is the case in Prader-Willi syndrome, which is caused by the deletion of the paternal copy of the imprinted SNRPN gene on chromosome 15q11.2; or by exposure to a teratogenic substance during embryonic development, as in fetal alcohol spectrum disorder.
Congenital malformations are defined as clinically significant abnormalities in either form or function. They result from localized intrinsic defects in morphogenesis, which were caused by an event that occurred in embryonic or early fetal life. This event may have been a disturbance of development from some unknown cause, but often mutations in developmental genes led to the abnormality. Extrinsic factors may cause disruptions of development by disturbing the development of apparently normal tissues. These disruptions may include amniotic bands, disruption of blood supply to developing tissues, or exposure to teratogens. A malformation sequence is the end result of a malformation that has secondary effects on later developmental events. An example is the Pierre Robin sequence. The primary malformation, failure of the growth of the mandible during the first weeks of gestation, results in micrognathia, which forces the normal-sized tongue into an unusual position. The abnormally placed tongue blocks the fusion of the palatal shelves, which normally come together in the midline to produce the hard and soft palate; this leads to the presence of a U-shaped cleft palate. After delivery, the normal-sized tongue in the smaller than normal oral cavity leads to airway obstruction, a potentially life-threatening complication. Pierre Robin sequence comprises a triad of anomalies (micrognathia, U-shaped cleft palate, and obstructive apnea) which results from a single malformation, the failure of the jaw to grow at a critical time during gestation. Many children with Pierre Robin syndrome have Stickler syndrome, an autosomal dominant disorder caused by mutations in collagen genes. Stickler syndrome also manifests with ocular and musculoskeletal abnormalities.
Deformations arise as a result of environmental forces acting on normal structures. They occur later in pregnancy or after delivery. For instance, plagiocephaly (rhomboid shaped head) may result from intrauterine positioning or from torticollis experienced in the newborn period. Deformations often resolve with minimal intervention, but malformations often require surgical and medical management.
Minor malformations, variants of normal that occur in less than 3% of the population, include findings such as single transverse palmar creases, low-set ears, or hypertelorism; when isolated, they have no clinical significance. A multiple malformation syndrome is the recognizable pattern of anomalies that results from a single identifiable underlying cause. It may involve a series of malformations, malformation sequences, and deformations. These syndromes often prompt a consultation with a clinical geneticist. Dysmorphology is the specialty focusing on recognition of patterns of malformations that occur in syndromes (Table 50-1).
An association differs from a syndrome in that in the former, no single underlying etiology explains the recognizable pattern of anomalies that occur together more often than would be expected by chance alone. The VACTERL association (vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb anomalies) is an example of a group of malformations that occur more commonly together than might be expected by chance. No single unifying etiology explains this condition, so it is considered an association.