Clinically evocated by association of
arthrogryposis, ocular signs, and growth failure. Many features are apparent
at birth. The disease involves head and neck (microcephaly,
micrognathia/retrognathia, upper lip overlaps the lower lip, sloping forehead, long
philtrum and prominent nasal root, large ear pinnae), CNS (mental retardation,
hemiparesis, hypoplasia of the optic tract, focal microgyria, corpus callosum
agenesis, seizures, infantile spasm, hypotonia, third ventricle subependymal focal
gliosis, cerebellar hypoplasia), eyes (cataracts, blepharophimosis,
microphthalmia, deep-set eyes, and nystagmus), skeleton (osteoporosis, vertebral
segmentation defects, kyphoscoliosis, coxa valga, shallow acetabular angle,
elbow and knee flexion contractures, camptodactyly, vertical talus, rocker-bottom feet,
longitudinal groove on the soles, posterior placement of the second metatarsal). Other
inconstant features can include widely spaced nipples, insulin resistance, hirsutism,
and heart defects. Early death, associated with feeding difficulties and pneumonia,
often occurs.