Premature aging is the hallmark of all types of
CS. CS I (type A or “classic” form) presents in infancy and is less severe
than CS II (type B or “congenital” or “connatal” form), which presents
earlier and is generally apparent already at birth. CS III (type C or
“late-onset” form) presents later in life, and there is no universal
agreement as to the existence of CS III. The classic form (type I) may involve the head and neck
(microcephaly, thickened calvarium, intracranial calcifications, mandibular
prognathism, loss of facial adipose tissue with wrinkled face, slender nose,
malformed ears, sensorineural hearing loss, hypoplastic teeth with caries,
delayed eruption of deciduous teeth), the nervous system (mental
retardation, leukodystrophy, normal pressure hydrocephalus, seizures,
nystagmus, ataxia, dysarthria, tremor, generalized weakness, peripheral
neuropathy), the eyes (“salt and pepper" retinal pigmentation, optic nerve
atrophy, strabismus, hypermetropia, corneal opacity, decreased lacrimation;
development of cataracts before the age of 3 years is associated with a severe course of
the disease and early mortality), the cardiovascular system (arterial
hypertension, arrhythmias, premature atherosclerosis), the genitourinary
tract (renal failure, proteinuria, cryptorchidism, micropenis), the
musculoskeletal system (short stature, vertebral anomalies with kyphosis, small squared-off
pelvis with hypoplastic iliac wings, mild-to-moderate limitation of joint
movements, sclerotic phalangeal epiphyses), and the skin (precocious senile
appearance [wrinkling], photosensitivity, scarring, poikiloderma, anhydrosis
and dry skin, thin and dry hair, decreased subcutaneous adipose tissue,
café-au-lait spots). Other features include hepatosplenomegaly with
elevated liver enzyme serum concentrations. There is no increase in
malignancies or susceptibility to infections. Death in CS I patients usually
occurs early in the second decade of life. Growth failure in patients with
congenital CS type II is obvious at birth (intrauterine and postnatal growth
retardation) or shortly after birth. Neurologic development is either absent
or severely delayed. Congenital cataracts or other structural ocular
anomalies occur in up to one third of patients. Arthrogryposis and/or early
joint contractures result in restricted movement and kyphoscoliosis. Death
usually occurs before 10 years of age, often as a result of pneumonia. In
several aspects, CS type II resembles the Pena-Shokeir Syndrome Type
II. A small subset of patients share some features of CS, but show normal
growth and neurologic development. These patients have been assigned the
diagnosis of “late-onset” CS or CS type III. However, the debate is ongoing
whether CS type III is in fact a form of CS or an entirely different
syndrome.