Autism-World

Infancy. The infant with WS is often born post-term, and is small for the family background. Feeding difficulties leading to failure to thrive are common, including gastro-esophageal (G-E) reflux, disordered suck and swallow, textural aversion, and vomiting. Prolonged colic (>4 months) may be related to G-E reflux, chronic constipation, and/or idiopathic hypercalcemia, which occurs in 15% of individuals with WS. Other medical problems that often occur in the first year include strabismus, chronic otitis media, rectal prolapse, inguinal hernia, and cardiovascular disease [Morris et al 1988]. Infants with WS are hypotonic and typically have hyperextensible joints, resulting in delayed attainment of motor milestones. Walking usually occurs by 24 months. Speech is also delayed, but later becomes a relative strength. Fine motor difficulties are present at all ages.

Cognitive abilities. Mental retardation, usually mild, occurs in 75% of individuals with WS. The cognitive profile is distinctive, consisting of strengths in verbal short-term memory and language, but extreme weakness in visuospatial constructive cognition. As a result, children with WS usually score higher on verbal subtests than on tests measuring visuospatial construction [Greer et al 1997 , Mervis et al 1998].

Academically, individuals with WS perform relatively well in reading, and adults may read at the high school level, though the range of achievement is wide. Reading skills correlate with cognitive ability rather than language-related skills [Levy et al 2003]. Difficulty with writing, drawing, and mathematics is significant; however, many adults with WS are able to perform simple addition.

Adaptive behavior is commensurate with IQ in children [Mervis et al 2001], but adaptive behavior is less than expected for IQ in adults [Davies et al 1997], adversely affecting the ability of adults with WS to function independently.

Unique personality. The characteristic personality profile of WS includes overfriendliness, excessive empathy, attention problems, and anxiety [Einfeld et al 2001 , Cassidy & Morris 2002 , Doyle et al 2004]. Other common behavior problems include sensory defensiveness, perseveration, unusual or restricted interests, sleep difficulties, and specific phobias (80%) [Dykens 2003 , Laws & Bishop 2004]. Compared to other children with disabilities, children with WS rate high on measures of the following: empathy, gregariousness, people-orientation, tenseness, sensitivity, and “visibility” (easily noticed) [Klein-Tasmin & Mervis 2003]. Anxiety is common in adults with WS (80%).

Cardiovascular disease. Elastin arteriopathy is present in about 75% of affected individuals and may affect any artery. Males are more likely to have severe cardiovascular disease than females [Sadler et al 2001].

Peripheral pulmonic stenosis (PPS) is common in infancy but usually improves over time.

The most common arteriopathy is supravalvular aortic stenosis (SVAS), which may worsen over time. The greatest morbidity results from this aortic narrowing, which can be either a discrete hourglass stenosis or diffuse aortic hypoplasia. If untreated, the resultant increase in arterial resistance leads to elevated left heart pressure, cardiac hypertrophy, and cardiac failure.

Individuals with combined SVAS and PPS (biventricular outflow tract obstruction) may develop biventricular hypertrophy and hypertension, increasing the risk for myocardial ischemia, dysrhythmias, and sudden death [Lacro & Smoot 2006]. Coronary artery stenosis has been implicated in some cases of sudden death in WS [Bird et al 1996]. The incidence of sudden death in one WS cohort of 293 was 1/1000 patient years, which is 25 to 100 times higher than the age matched population [Wessel et al 2004].

Hypertension is common in adolescents and adults [Broder et al 1999 , Giordano et al 2001 , Eronen et al 2002], and may be secondary to renal artery stenosis in some cases [Deal et al 1992].

Mitral valve prolapse and aortic insufficiency have been reported in adults [Morris et al 1990 , Kececioglu et al 1993].

Stenosis of the mesenteric arteries may contribute to abdominal pain.

Neurovascular abnormalities are rarely reported but may result in stroke [Ardinger et al 1994 , Soper et al 1995 , Cherniske et al 2004].

Eye, ear, nose, and throat. Hyperopia is found in 50% of individuals with WS and strabismus in 50% [Kapp et al 1995]. Cataracts have been reported in adults [Cherniske et al 2004].

Chronic otitis media is seen in 50% of affected individuals. Increased sensitivity to sound is common (90%) and individuals with WS report discomfort at 20 decibels (db) lower than controls [Gothelf et al 2006]. Many report specific phobias for certain sounds [Levitin et al 2005].

Progressive sensorineural hearing loss has been demonstrated [Marler et al 2005 , Gothelf et al 2006]. Mild to moderate high-frequency sensorineural hearing loss is common in adults, as is excessive build-up of ear wax [Cherniske et al 2004].

Most individuals have a hoarse or low-pitched voice; vocal cord abnormalities secondary to elastin deficiency are likely causative [Vaux et al 2003].

Dental problems include microdontia, enamel hypoplasia, and malocclusion [Hertzberg et al 1994]. One or more permanent teeth are missing in 40% of individuals with WS [Axelsson et al 2003].

Gastrointestinal difficulties. Individuals with WS have sensory defensiveness, both auditory [Van Borsel et al 1997] and tactile. The difficulty with food textures leads to problems in transitioning from breast milk or formula to solid foods in infancy.

Chronic abdominal pain is a common complaint of children and adults with WS; possible causes include G-E reflux, hiatal hernia, peptic ulcer disease, cholelithiasis, diverticulitis, ischemic bowel disease, chronic constipation, and somatization of anxiety. The prevalence of diverticulitis is increased in adults with WS [Partsch et al 2005].

Hypercalcemia may contribute to irritability, vomiting, constipation, and muscle cramps; it is more common in infancy but may recur in adults [Morris et al 1990 , Pober et al 1993].

In one study, the incidence of celiac disease was increased in children with WS (9.6% vs 0.5% in the general population) [Giannotti et al 2001].

Urinary tract abnormalities. Urinary frequency and enuresis (50%) are common in children with WS. Structural abnormalities of the urinary tract are found in 35-50%, renal artery stenosis in 50%, bladder diverticulae in 40%, chronic urinary tract infections in 30% of adults, and nephrocalcinosis in fewer than 5% [Pober et al 1993 , Pankau et al 1996 , Sforzini et al 2002 , Sammour et al 2006]. Bladder capacity is reduced and detrusor overactivity is observed in 60% [Sammour et al 2006].

Musculoskeletal/neurologic problems. The hypotonia and lax joints of the young child lead to abnormal compensatory postures to achieve stability. Older children and adults with WS typically have hypertonia and hyperactive deep-tendon reflexes. Gradual tightening of the heel cords and hamstrings occurs, resulting in a stiff and awkward gait, kyphosis, and lordosis by adolescence [Morris et al 1988 , Kaplan et al 1989]. Fine motor function is impaired, leading to difficulty with tool use and handwriting at all ages.

Cerebellar signs in adults include ataxia and tremor [Pober & Szekely 1999].

Growth. Individuals with WS are short for their family background. Specific growth curves for WS are available [Morris et al 1988 , Saul et al 1988]. Failure to thrive is observed in 70% of infants. The growth pattern is characterized by prenatal growth deficiency, poor weight gain and poor linear growth in the first four years, a rate of linear growth that is 75% of normal in childhood, and a brief pubertal growth spurt. The mean adult height is below the third centile.

Puberty usually occurs early [Partsch et al 2002], but true precocious puberty is rare.

Endocrine problems. Endocrine abnormalities include idiopathic hypercalcemia (15%), hypercalciuria (30%), hypothyroidism (10%), and early (though not precocious) puberty (50%). An increased frequency of subclinical hypothyroidism, abnormal oral glucose tolerance tests, and diabetes mellitus is observed in adults with WS [Cherniske et al 2004].

Other. The hair grays prematurely [Morris et al 1988], but there is not yet sufficient evidence to suggest that WS is a premature aging syndrome [Pober 2006].

Neuroimaging. Functional MRI studies demonstrate isolated hypoactivation in the parietal portion of the dorsal stream in the visual processing pathway. Structural MRI shows gray matter volume reduction in the adjacent parietooccipital/intraparietal sulcus, demonstrating the neural basis of the visual processing dysfunction in WS [Meyer-Lindenberg et al 2004 , Eckert et al 2005 , Kippenhan et al 2005].

This entry was posted on Thursday, August 16th, 2007 at 9:50 pm and is filed under Williams Syndrome.