Porth's Essentials of Pathophysiology, 4e

109

Genetic and Congenital Disorders

C h a p t e r 6

EYE

Lens dislocation, myopia

SKELETAL DEFORMITY

Pectus carinatum (pigeon chest), pectus excavatum (funnel chest)

Vertebral deformity (kyphosis, scoliosis)

Long arms, arm span exceeds height

CARDIOVASCULAR

Aortic aneurysm, floppy valves

the trunk (Fig. 6-3). The subcutaneous lesions grow just below the skin; they are firm and round, and may be pain- ful. Plexiform neurofibromas involve the larger peripheral nerves. They tend to form large tumors that cause severe disfigurement of the face, overgrowth of an extremity, or skeletal deformities such as scoliosis. Pigmented nodules of the iris (Lisch nodules), which are specific to NF-1, usu- ally are present after 6 years of age. They do not pres- ent any clinical problem but are useful in establishing a diagnosis. A second major component of NF-1 is the presence of large (usually ≥ 15 mm in diameter), flat cutaneous pig- mentations, known as café au lait spots . They are usu- ally a uniform light brown in whites and darker brown in persons of color, with sharply demarcated edges. Although small single lesions may be found in normal children, larger lesions or six or more spots larger than 1.5 cm in diameter suggest NF-1. The skin pigmenta- tions become more evident with age as the melanosomes in the epidermal cells accumulate melanin. Children with NF-1 are also susceptible to neuro- logic complications. There is an increased incidence of learning disabilities, attention deficit disorders, and abnormalities of speech. Complex partial and general- ized tonic-clonic seizures are a frequent complication. Neurofibromatosis-1 is also associated with increased incidence of other neurogenic tumors, including menin- giomas, optic gliomas, and pheochromocytomas. 2 FIGURE 6-3. Neurofibromatosis, type I. Multiple cutaneous neurofibromas are noted on the face and trunk. (From Peiper S, Rubin DS. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams &Wilkins; 2012:238.)

Dissecting aortic aneurysm with exsanguination

Joint hypermobility, especially fingers, wrists, and knees

FIGURE 6-2. Clinical features of Marfan syndrome.

There are at least two genetically and clinically distinct forms of the disorder: type 1 NF (NF-1), also known as von Recklinghausen disease , and type 2 bilateral acoustic NF (NF-2). Both of these disorders result from a genetic defect in a tumor-suppressor gene that regulates cell dif- ferentiation and growth. The gene for NF-1 has been mapped to chromosome 17 and the gene for NF-2 to chromosome 22. 3 Type 1 NF is a relatively common disorder, with a fre- quency of 1 in 3500. 3 Approximately 50% of cases have a family history of autosomal dominant transmission, and the remaining 50% appear to represent a new mutation. The disorder is characterized by multiple neural tumors (neurofibromas) dispersed anywhere on the body; numer- ous pigmented skin lesions, some of which are café au lait spots; and pigmented nodules (Lisch nodules) of the iris. 7–11 The cutaneous neurofibromas, which vary in number from a few to many hundreds, manifest as soft, pedunculated lesions that project from the skin. They are the most common type of lesion, often are not apparent until puberty, and are present in greatest density over