Central Nervous System
Megalencephaly
The M in MLC stands for “megalencephaly”, the enlargement of the brain
Ataxia
Slow, progressive and early-onset cerebellar ataxia has been noted in many patients
Spasticity
Patients with MLC often have muscle spasms
Seizures
Delay in motor development
 Mild mental retardation
Diffuse swelling of cerebral white matter
 Large subcortical cysts in frontal and temporal lobes
Patients develop cysts on the tips of the temporal and subcortical area
Diffuse spongiform leukoencephalopathy
Vacuolizing myelinopathy
The protective myelin sheath on neurons pulls away from their cells forming small holes in nerve fibers – in turn affecting coordination and walking ability. Genetics
It is associated with MLC1. The MLC1 gene is located in chromosome 22q13.33 and is in the genomic coordinates 22:50,059,390 – 50,085874. The gene contains 12 exons and that contain a start codon in exon 2 and an untranslated region in the 3’ end. The MLC1 gene product is a 377 amino acid protein highly expressed in the brain. The disease is caused by a homozygous or compound heterozygous mutation in the gene, MLC1. Previous research indicates that deficiency of cell surface protein expression of the MLC1 gene is the basis for the disorder. The mutant protein is expressed in intracellular compartments reducing the membrane surface expression when compared to the wild type. Diagnosis
Diagnosis of Megalencephalic leukoencephalopathy with subcortical cysts is made with a combination of physical and clinical evaluations. The presence of frontal and temporal subcortical cysts is the main factor when diagnosing a patient with this disease.
Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning "curving of joints" (arthron, "joint"; grȳpōsis, late Latin form of late Greek grūpōsis, "hooking").Children born with one or more joint contractures have abnormal fibrosis of the muscle tissue causing muscle shortening, and therefore are unable to perform active extension and flexion in the affected joint or joints.AMC has been divided into three groups: amyoplasia, distal arthrogryposis, and syndromic. Amyoplasia is characterized by severe joint contractures and muscle weakness. Distal arthrogryposis mainly involves the hands and feet. Types of arthrogryposis with a primary neurological or muscle disease belong to the syndromic group. Signs and symptoms
Often,  every joint in a patient with arthrogryposis is  affected; in 84% all limbs are involved, in 11% only the legs, and in 4% only the arms are involved. Every joint in the body, when affected, displays typical signs and symptoms:  for example, the shoulder (internal rotation); wrist (volar and ulnar); hand (fingers in fixed flexion and thumb in palm); hip (flexed, abducted and externally rotated, frequently dislocated); elbow (extension and pronation) and foot clubfoot and less commonly congenital vertical talus.Range of motion can be different between joints because of the different deviations. Some types of arthrogryposis like amyoplasia have a symmetrical joint/limb involvement, with normal sensations.