The main clinical features of PMLD are hypomyelination, i.e. permanent failure to build up myelin in the brain, weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), intellectual disability. Furthermore patients present with delayed and impaired development of speech and motor skills, such as sitting, crawling and walking. Muscle stiffness (spasticity) usually develops as children get older reverting the initial general muscle hypotonia. Neurological problems in individuals with PMLD become manifest from birth or in early infancy.
Hereditary spastic paraplegia 44 (SPG44) is a hypomyelinating leukodystrophy (white matter disease with permanent myelin deficit in the brain). It is characterized by slowly progressive weakness and spasticity (muscle stiffness) of the lower limbs. The rate of progression and severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms. In some forms of the disease, urine incontinence or other forms of bladder dysfunction may occur. Moreover, weakness and stiffness may progress and involve other parts of the body.
Hereditary lymphedema type 1C (LMPH1C) is caused by anatomical or functional defects in the lymphatic system, resulting in chronic swelling of body parts. There may be accompanying nail and skin changes (e.g., cellulitis). The disease, with variable severity, usually begins at birth or in early childhood, but rarely occurs later.
GJC2