Clinical signs of Alström Syndrome

The first sign usually noticed in affected children is an involuntary rapid movement of the eye (nystagmus) and light sensitivity which begins in infancy and eventually leads to a degeneration of the retina, the thin, light sensitive lining at the back of the eye (retinopathy) and blindness.

Congestive heart failure resulting from dilated cardiomyopathy (dysfunctioning of the heart muscle) is often seen, either in early infancy or adolescence.

As infants and toddlers, children are generally overweight. Hearing impairment usually begins before the children are 10 years old. Later, in young adulthood, children become insulin resistant, develop high levels of insulin in the blood, and eventually type 2 diabetes mellitus.

Other findings observed in some Alström Syndrome patients include a darkening of areas of the skin, called acanthosis nigricans, scoliosis or curvature of the spine, short stature, an under active thyroid gland, pulmonary problems, and elevation of enzymes in the liver. Kidney or liver failure can occur in the second to fourth decade of life.

Considerable variability exists in the expression of the clinical signs of Alström Syndrome, even among siblings. Not all people who have Alström Syndrome will experience all of these features.

The following manifestations are observed in most Alström Syndrome cases:

• nystagmus and photodysphoria in early infancy
• progressive pigmentary retinopathy (cone-rod dystrophy) leading to blindness
• childhood obesity, often moderating to high-normal weight in adulthood
• mild to moderate bilateral sensorineural hearing loss
• congestive heart failure secondary to dilated cardiomyopathy in infancy or early adulthood
• normal extremities / absence of polydactyly or syndactyly
• hyperinsulinemia / insulin resistance
• non-insulin dependent diabetes mellitus (Type 2 diabetes or NIDDM) developing in early adulthood
• progressive chronic nephropathy that presents as tubular dysfunction
• normal intelligence with some reports of delayed early developmental milestones

Manifestations present in some but not all cases include:

• hypothyroidism  
• elevation of hepatic enzymes
• steatosis
• splenomegaly  
• portal hypertension  
• hepatic dysfunction
• alopecia
• low levels of growth hormone
• short stature
• advanced bone age 
• scoliosis and/or kyphosis
• developmental delay 
• hypertension
• hirsutism
• hyperlipidemia
• hypertriglyceridemia
• atherosclerotic disease
• muscle dystonia
• acanthosis nigricans
• hyperuricemia
• male hypogenitalism
• irregular menses   
• hyperostosis frontalis interna
• diabetes insipidus
• frequent urinary tract infections
• gastrointestinal reflux
• asthma or respiratory problems
• hypersecretory lungs 
• COPD