The main symptoms of WWS are Muscular dystrophy (progressive Degeneration and Weakness of the voluntary muscles) and abnormalities of the brain and eyes. Symptoms of WWS are congenital (present at birth), and some of the brain abnormalities can be detected by prenatal ultrasound and/or fetal MRI in the later stages of pregnancy.
Individuals with WWS have congenital muscular dystrophy, or a weakening and loss of muscle at birth. Muscular dystrophy causes affected infants to have severe Hypotonia (low muscle tone), muscle weakness, and atrophy (wasting away) which typically get worse over time. Some affected individuals develop contractures (abnormally fixed joints) that occur when thickening and shortening of tissue, such as muscle fibers, deform and restrict movement of an affected area.
Affected infants usually have a variety of serious brain findings, including type II lissencephaly (smooth brain), hydrocephalus (enlarged ventricles) and malformations in the back of the brain. Type II lissencephaly is also called cobblestone lissencephaly because the surface of the brain has a cobblestone appearance due to the collection of clumps of neurons (brain cells) at the surface. Hydrocephalus, which is characterized by having too much cerebrospinal fluid in the ventricles of the brain causing an enlargement, can be quite severe and lead to an abnormally large head. Malformations of the back portions of the brain can include hypoplasia (underdevelopment) of the cerebellum and brainstem. The cerebellum helps coordinate voluntary muscle movements, while the brainstem helps control basic functions such as breathing, salivation and heart rate. These posterior malformations can involve an abnormally enlarged space at the back of the brain, sometimes referred to as Dandy-Walker malformation. In some individuals with WWS, there is an encephalocele, which is a protrusion of part of the brain through the skull bone. Individuals with WWS may also have absence of the corpus callosum, which is the band of white matter that normally connects the two brain hemispheres.
The combined brain and muscle abnormalities lead to significant delays in reAching developmental milestones (e.g., sitting up, grabbing objects, crawling, talking) and can be so severe as to cause difficulties in breathing and swallowing. Children born with WWS display Intellectual disability and often have seizures.
The Eye abnormalities associated with WWS vary widely from person to person and can include any of the following: microphthalmia (abnormally small eyes), optic nerve hypoplasia (absent or underdeveloped optic nerves), retinal dysplasia (malformation of the retina which could cause the retina to become detached) and malformations of the fluid-filled space within the eyes behind the cornea and in front of the iris. Additional eye symptoms can include cataracts, coloboma (a cleft or loss of tissue of the retina or iris), buphthalmos (large and protruding eyes) or glauComa (increased pressure within the eyes). Most of these abnormalities lead to partial or complete blindness.
Occasionally, additional symptoms in different body systems can also be present. In some affected children, genitourinary abnormalities can occur, causing urinary tract blockage and kidney pelvic dilation (hydronephrosis) or failure of the testes to descend into the scrotum in males (cryptorchidism). Some affected children have other features, such as low-set or prominent ears, cleft lip or palate or cochlear hypoplasia (inner ear malformation).