Multifactorial Inheritance Disorders
Multifactorial inheritance disorders are caused by multiple genes and, in many cases, environmental factors. The exact number of genes contributing to multifactorial traits is not known, and these traits do not follow the same clear-cut pattern of inheritance as do single-gene disorders. Disorders of multifactorial inheritance can be expressed during fetal life and be present at birth, or they may be expressed later in life. Congenital disorders that are thought to arise through multi- factorial inheritance include cleft lip or palate, clubfoot, congenital dislocation of the hip, congenital heart disease, pyloric stenosis, and urinary tract malformation. Environmental factors are thought to play a greater role in disorders of multifactorial inheritance that develop in adult life, such as coronary artery disease, diabetes mellitus, hypertension, and cancer.
Although multifactorial traits cannot be predicted with the same degree of accuracy as mendelian single-gene mutations, characteristic patterns exist. First, multifactorial congenital malformations tend to involve a single organ or tissue derived from the same embryonic developmental field. Second, the risk of recurrence in future pregnancies is for the same or a similar defect. This means that parents of a child with a cleft palate defect have an increased risk of having another child with a cleft palate, but not with spina bifida. Third, the increased risk (compared with the general population) among first-degree relatives of the affected person is 2% to 7%, and among second-degree relatives, it is approximately one half that amount. The risk increases with increasing incidence of the defect among relatives. This means that the risk is greatly increased when a second child with the defect is born to a couple. The risk also increases with severity of the disorder and when the defect occurs in the sex not usually affected by the disorder.
Cleft Lip and Cleft Palate
Cleft lip with or without cleft palate is one of the most common birth defects, occurring in about 0.1% of all pregnancies. It is also one of the more conspicuous birth defects, resulting in an abnormal facial appearance and defective speech. Cleft lip with or without cleft palate is more frequent among boys, whereas isolated cleft palate is twice as common among girls. The incidence of cleft palate is approximately 1 in 2500.
Developmentally, the defect has its origin at about the 35th day of gestation when the frontal prominences of the craniofacial structures fuse with the maxillary process to form the upper lip. This process is under the control of many genes, and disturbances in gene expression (hereditary or environmental) at this time may result in cleft lip with or without cleft palate (Fig. 7.6). The defect may also be caused by teratogens (e.g., rubella, anticonvulsant drugs) and is often encountered in children with chromosomal abnormalities.
Cleft lip and palate defects may vary from a small notch in the vermilion border of the upper lip to complete separation involving the palate and extending into the floor of the nose. The clefts may be unilateral or bilateral and may involve the alveolar ridge. The condition may be accompanied by deformed, supernumerary, or absent teeth. Isolated cleft palate occurs in the midline and may involve only the uvula or may extend into or through the soft and hard palates.
A child with cleft lip or palate may require years of special treatment by medical and dental specialists, including a plastic surgeon, pediatric dentist, orthodontist, speech therapist, and nurse specialist. The immediate problem in an infant with cleft palate is feeding. Nursing at the breast or nipple depends on suction developed by pressing the nipple against the hard palate with the tongue. Although infants with cleft lip usually have no problems with feeding, those with cleft palate usually require specially constructed, soft artificial nipples with large openings and a squeezable bottle.
Major advances in the care of children born with cleft lip and palate have occurred within the last quarter of the 20th century. Surgical closure of the lip is usually performed by 3 months of age, with closure of the palate usually done before 1 year of age. Depending on the extent of the defect, additional surgery may be required as the child grows. In some situations, the palate is repaired prior to the cleft lip, and results indicate that the palate surgery is easier when done prior to the cleft lip repair. Also the time between surgeries when cleft palate is repaired prior to lip repair is shorter. Displacement of the maxillary arches and malposition of the teeth usually require orthodontic correction.
Cleft lip and palate can also cause speech defects. The muscles of the soft palate and the lateral and posterior walls of the nasopharynx constitute a valve that separates the nasopharynx from the oropharynx during swallowing and in the production of certain sounds.