OMIM ID:
Cerebral Palsy, Spastic Quadriplegic, 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
One family with 4 affected sibs has been reported but without detailed information on ophthalmological findings. Strabismus reported as exotropia in one individual, and “convergent retraction nystagmus” in another was present. Supranuclear gaze palsy was described in one individual.
Systemic Features
Borderline microcephaly has been reported. Evidence for global neurologic disease, primarily spasticity, may be present as early as 3 months of age. Intellectual disability ranges from borderline to severe. Progression is somewhat variable but by the second decade there may be sufficient spastic quadriparesis and cognitive impairment that full time assistive care is required. Dysarthria and dysphagia are also features and gastrostomy feeding tubes may be required to maintain nutrition. Seizures are uncommon.
The MRI does not show major structural abnormalities and an EEG in one patient revealed only bifrontal spike-waves.
Genetics
Inheritance
This condition is caused by homozygous mutations in the ADD3 gene (10q24).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.