Spastic Paraplegia 50
Synonyms of Spastic Paraplegia 50
AP4M1-associated hereditary spastic paraplegia
AP-4 deficiency syndrome
Spastic paraplegia 50 (SPG50) is a slowly-progressing neurodegenerative disorder that generally presents with global developmental delay, moderate to severe intellectual disability, impaired/absent speech, small head size (microcephaly), seizures, and progressive motor symptoms. Hypotonia (low-muscle tone) develops into hypertonia (high-muscle tone), resulting in spasticity of the legs that leads to non-ambulation and wheelchair reliance. Spasticity may progress to the upper extremities, leading to the partial or total loss of use of all four limbs and torso (tetraplegia).
Signs & Symptoms
Most children with SPG50 have:
• a “floppy” appearance in infancy due to low muscle tone
• increasing spasticity and paralysis in the lower limbs starting in early childhood
• intellectual disability
• delayed motor development
• poor or absent speech development
Other known features can include the following (not every child will have these features:
• short stature
• late walking and later loss of the ability to walk independently
• dystonia (involuntary muscle contractions)
• ataxia (impaired balance and coordination)
• seizures including frequent seizures in the setting of fever
Some children may also have facial differences that can include:
• high palate
• wide nasal bridge
• bulbous nose
• wide mouth
• protruding tongue
• short philtrum (the groove between the bottom of the nose and top of the lips)
• narrow forehead
• flat feet or club feet
SPG50 is inherited in an autosomal recessive manner. The gene that is involved is AP4M1. A gene with a disease-causing (pathogenic) mutation must be inherited from each parent to result in manifestations of symptoms. Parents carrying a mutated gene have a 25% chance of having an affected child, a 50% chance of having an unaffected carrier child and a 25% chance of having a child who is unaffected and does not carry a mutated gene.
SPG50 affects males and females of ethnic groups from around the world.
The prevalence of SPG50 is unknown. SPG50 is likely under-recognized since the symptoms (phenotypic spectrum) largely overlaps with that of cerebral palsy and, in the absence of genetic testing, many patients may be misdiagnosed as having cerebral palsy.
AP-4-associated hereditary spastic paraplegia (HSP) is a group of slowly-progressing neurodegenerative disorders that generally present with global developmental delay, moderate to severe intellectual disability, impaired/absent speech, microcephaly, seizures, and progressive motor symptoms. The conditions included in this group are SPG47, SPG50, SPG51 and SPG52 and all have similar symptoms. These conditions are inherited in an autosomal recessive pattern and are caused by mutations in genes that result in production of an abnormal adaptor protein complex 4.
Since many of the initial clinical manifestations of SPG50 are nonspecific and may resemble other disorders characterized by spasticity, developmental delay / intellectual disability, and seizures, the diagnosis is often only made after further diagnostic testing. This may include a brain MRI showing characteristic features such as a thin corpus callosum, wide lateral ventricles and changes in the white matter. A definitive diagnosis is reached by genetic testing.
Treatment: management of symptoms
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as mental health services, special educators, and sensory-impairment specialists.
Ages 3-5 years. In the United States, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, and/or cognitive delay. The early intervention program typically assists with this transition.
Ages 5-21 years. In the United States, an IEP based on the individual’s level of function should be developed by the local public school district and will dictate specially designed instruction/related services. Discussion about transition plans including financial and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.
Gross motor dysfunction
• Physical therapy is recommended to maximize mobility.
• Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.
Oral-motor dysfunction. Oral-motor dysfunction should be reassessed in regular intervals and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained.
Communication issues. Speech therapy is recommended. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties.
Above leveraged from NORD: https://rarediseases.org/rare-diseases/spastic-paraplegia-50/