Neurologic Complications of Down Syndrome
Neurologic Complications of Down Syndrome
Down syndrome (DS) is the most common genetically inherited disorder in the general population, with a prevalence of 1 in 700 live births. Children with DS are at risk for a variety of medical complications that may affect the cardiovascular, endocrine, auditory, musculoskeletal, and neurologic systems. Here I focus on the neurologic issues that may arise while providing medical care to children with DS. The complications are considered in the chronological order in which they tend to appear.
1. Hypotonia. Newborns with DS may exhibit marked hypotonia that usually improves during childhood. The low tone causes ligamentous laxity and delays the acquisition of motor milestones, which, nonetheless, follow the same developmental trajectory seen in a normal child, albeit at a slower pace.1 Gait abnormalities are common in children with DS even when they are older; prominent are longer stance time and decreased hip movements. The anatomical basis for the low tone is believed to be the result of microscopic changes in the development of the cerebellum.2
2. Epilepsy occurs in 1% to 13% of children with DS and often demonstrates a bimodal distribution with peaks in infancy and in adulthood after the age of 30 years.3 Infantile spasms. As the name implies, infantile spasms (IS) usually become evident before the first year of life. IS is identified by brief clusters of seizures characterized by rapid head jerks with flexion of the arms (“flexor spasms”). When they first emerge, the spasms can be mistaken for a startle response, gastroesophageal reflux, or hiccups. The most effective treatment options are adrenocorticotropin hormone (ACTH) in the injectable form on a daily basis for 6 to 8 weeks or oral vigabatrin (SabrilR) for approximately 2 to 4 years. The most common adverse effects of ACTH are predisposition to infection, hypertension, gastritis, and irritability. Vigabatrin has been associated with moderate loss of vision in 16% of cases and with profound loss of vision, which unfortunately tends to be irreversible, in 3% of cases.4 Regular assessment by a pediatric ophthalmologist is essential for children treated with this agent. Most children with DS and concomitant IS respond well to treatment compared with those who have IS associated with other etiologies.
Other seizure types. Epilepsy in young adulthood is often of the myoclonic or generalized tonic clonic type.5
3. Impaired intellectual development is universal in DS, although it can vary in degree. Linguistic abilities tend to be affected disproportionately to overall cognitive abilities.6 The characteristic neuropathology of Alzheimer disease is usually evident by age 40 years in patients with DS. Clinically, however, not all individuals will exhibit the hallmark features of the disease. Anticholinergic agents such as donepezil may have positive effects on the memory challenges these patients face.7
4. Psychiatric problems. Current prevalence estimates of neurobehavioral and psychiatric comorbidity in children with DS range from 18% to 38%.8 Included in this category are depression, ADHD, oppositional behavior, impulsive tendencies, and disruptive behaviors. The incidence of autism spectrum disorders (ASD) in patients with DS has been reported to be 18%—several times higher than that found in the general population.9 Parents are usually cautious about initiating psychotropic medications and prefer to hold them as a last resort after behavioral interventions have failed. Early recognition and medical treatment of emotional and mood disorders, however, may be beneficial for the well-being of both child and family. Stimulants and atomoxetine are helpful for hyperactivity. Atypical neuroleptics for ASDs, selective serotonin reuptake inhibitors for depression, and benzodiazepines for agitation and anxiety are useful options.
5. Cervical cord compression. Toddlers and school-aged children with DS should be screened for atlantoaxial subluxation using lateral radiographs of the neck in flexion and extension. Approximately 10% to 20% of children have atlantoaxial subluxation, while 3% display cervical myelopathy.10 The average age of onset of myelopathy is 10.5 years. Surgical stabilization is required to avoid quadriplegia if instability is noted and there are signs of spinal cord compression. Examination findings that might lead to suspicion for myelopathy are brisk deep tendon reflexes in the extremities, upgoing plantar responses, and new-onset bladder/bowel disturbances.
6. Cardiac defects predispose children with DS to stroke. Atrioventricular septal defects are the most common (seen in 50% of individuals) and cerebral vasculopathy is also common. A classic complication that leads to stroke in children with DS is moyamoya syndrome. Moyamoya syndrome is a cerebrovascular disorder characterized by progressive non-inflammatory, non-atherosclerotic occlusion of bilateral intracranial arteries with compensatory formation of fragile arterial collateral vessels (Figure) that maintain cerebral circulation. The most common presenting feature is ischemic stroke, which usually occurs between the ages of 5 and 7 years.11 Stroke can be precipitated by crying, coughing, or straining. Surgical measures offer the best outcome for children with recurrent strokes secondary to underlying moyamoya vasculopathy.
7. Visual and hearing impairment. Vision impairment may manifest as strabismus, cataracts, or glaucoma. Hearing loss may be the result of recurrent otitis media in the younger age-group. All patients with DS must have regular screening for hearing and vision.
The American Academy of Pediatrics’ guidelines for the care of children with DS offer a valuable clinical resource to guide screening and selection of appropriate intervention.12
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12. Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics. 2011;128:393-406.