Basal-cell nevus syndrome. This condition is transmitted as an autosomal dominant trait and is characterized by superficial pits in the palms and soles; multiple solid or cystic tumors over the head, face, and neck appearing in infancy or early childhood; cognitive impairment in some cases; frontoparietal bossing; hypertelorism; and kyphoscoliosis.
Congenital ichthyosis, hypogonadism, and mental retardation. This disorder is inherited as a sex-linked recessive trait. Aside from the characteristic triad of anomalies, there are no special features.
Xeroderma pigmentosum. The genetic pattern of inheritance is autosomal recessive. Skin lesions appear in infancy, taking the form of erythema, blistering, scaling, scarring, and pigmentation on exposure to sunlight; old lesions are telangiectatic and parchment-like, covered with fine scales; skin cancer may develop later; loss of eyelashes, dry bulbar conjunctivae; microcephaly, hypogonadism, and cognitive impairment (50 percent of cases). Kanda and associates classify this disease with what in the past had been called DeSanctis-Cacchione syndrome of “xerodermic idiocy” and believe the basic mechanism to be a faulty repair of DNA. They described two young adults with low intelligence, evidence of spinal cord degeneration, and peripheral neuropathy. The peripheral nerve lesions resembled those of amyloidosis, Riley-Day syndrome, and Fabry disease in that there was a predominant loss of small fibers. Other variants are described. It is known that mutations in DNA-repair genes are the cause of xeroderma pigmentosa.
Sjögren-Larsson syndrome. Autosomal recessive with congenital ichthyosiform erythroderma, normal or thin scalp hair, sometimes defective dental enamel, pigmentary degeneration of retinae, spastic legs, and cognitive impairment.
Poikiloderma congenitale (Rothmund-Thompson syndrome). Autosomal recessive heredity; appearance of skin changes from the third to sixth months of life; diffuse pink coloration of cheeks spreading to ears and buttocks, later replaced by macular and reticular pattern of skin atrophy mixed with striae, telangiectasia, and pigmentation; sparse hair in half of the cases; cataracts; small genitalia; abnormal hands and feet; short stature; and cognitive impairment.
Linear sebaceous nevus syndrome. Here there is a linear nevus of one side of face and trunk, lipodermoids on bulbar conjunctivae, vascularization of corneas, mental retardation, focal seizures, and spike and slow waves in the EEG. Causative mutations occur in the HRAS, KRAS, and NRAS oncogenes, and interestingly, these mutations occur after fertilization (i.e., they are not inherited) and are only present in some cells (mosaicism).
Incontinentia pigmenti (Bloch-Sulzberger syndrome). Only females are affected; appearance of dermal lesions in first weeks of life; vesicles and bullae followed by hyperkeratoses and streaks of pigmentation, scarring of scalp, and alopecia; abnormalities of dentition; hemiparesis; quadriparesis; seizures; cognitive impairment; and up to 50 percent eosinophils in blood. This disease is now known to be caused by mutations in the NEMO (NF-κB essential modulator) gene.
Focal dermal hypoplasia. Also a disease limited to females. Areas of dermal hypoplasia with protrusions of subcutaneous fat, hypoand hyperpigmentation, scoliosis, syndactyly in a few, short stature, thin body habitus. There is occasionally cognitive impairment.