Williams syndrome (Williams–Beuren syndrome) is a rare neurodevelopmental disorder characterized by mental retardation, hypercalcemia of infants, heart defects, characteristic facial features ("elfin" facial appearance) and failure to thrive. It is caused by a deletion on chromosome 7.
The clinical features of Williams syndrome are manifold and include the following.
- Distinct “elfin” facial features  comprising of low set nasal bridge, broad nasal tip, broad forehead and broad lips. The mouth may be wide and there may be fullness in the cheeks.
- Dental abnormalities (in particular crooked or missing teeth)
- The birth weight may be low.
- Developmental delay may be observed. The milestones of walking and talking are often late .
- The patient may have soft and loose skin.
- Short stature may be observed.
- Microcephaly is seen in one third of the patients.
- Visual defects may also be present, particularly strabismus, esotropia, nystagmus and abnormal visual processing
- Recurrent middle ear infections in childhood may have occurred
- Sensorineural hearing loss may be present.
- There may be associated connective tissue abnormalities in the digestive and urinary system such as sigmoid and bladder diverticula .
- The IQ level may be low, however this parameter has great variations from patient to patient. Verbal skills of the patient are normal.
- Cardiac abnormalities including the following may be present: Supravalvular aortic stenosis (SVAS) leading to chest pain, dyspnea and ultimately, congestive cardiac failure , pulmonary stenosis, coronary insufficiency and ischemia, ventricular hypertrophy
Other clinical features in these patients include:
- Visual-spatial incoordination (difficulty while drawing or solving puzzles)
- Hypercalcemia (transient)
- Learning difficulties 
- Difficulty in descending the stairs
- Attention deficit disorder (ADD) and autism (in 50% of the patients)
- Undue anxiety
- Phobias (eg. phonophobia)
- Behavioral impacts: Highly sociable, love for arts and music, hyperreactivity to negative social cues, inability to adjust in competitive environments, extremely sensitive, trusting
Entire Body System
- Short Stature
stature, and specific intellectual disabilities (such as visual spatial problems). [ncbi.nlm.nih.gov]
ウィキペディア 分類 病気, developmental defect during embryogenesis 上位クラス chromosomal deletion syndrome, 大動脈弁上狭窄症, syndromic developmental defect of the eye, multiple congenital anomalies/dysmorphic syndrome-intellectual disability, malformation syndrome with short [commons.wikimedia.org]
Affected people may also have increased calcium levels in the blood (hypercalcemia) in infancy, developmental delays, problems with coordination, and short stature. [malacards.org]
- Feeding Difficulties
Williams-Beuren Syndrome (WBS) is a well-described microdeletion syndrome characterized by specific dysmorphic facial features, peripheral pulmonic stenosis, supravalvular aortic stenosis, hypercalcemia, feeding difficulties, gastroesophageal reflux, [ncbi.nlm.nih.gov]
A combination of specific facial characteristics including a stellate pattern in the iris, long philtrum and puffiness around the eyes; cardiovascular disease - especially aortic or pulmonary stenosis; feeding difficulties (in infants) and developmental [web.archive.org]
Feeding difficulties tend to resolve as the children get older. As toddlers, developmental delays are often noticed; major milestones such as walking and talking often occur 1-2 years later than expected. [williamssyndrome.org.au]
Fatigue is difficult to treat. [theconversation.com]
"They get easily fatigued, and we're still trying to understand why. There's also a higher incidence of diabetes and hypothyroidism, as well as cardiovascular disease." And behaviorally? "Friendliness, oh my gosh. Lots, lots of social interest. [theatlantic.com]
She had initial complaints of abdominal swelling, constipation, and fatigue for 4 days. [ijmpo.org]
- Multiple Congenital Anomalies
ウィリアムズ症候群 neurodevelopmental disorder メディアをアップロード ウィキペディア 分類 病気, developmental defect during embryogenesis 上位クラス chromosomal deletion syndrome, 大動脈弁上狭窄症, syndromic developmental defect of the eye, multiple congenital anomalies/dysmorphic syndrome-intellectual [commons.wikimedia.org]
Winter and Michael Baraitser, A catalogue of multiple congenital anomaly syndromes, Multiple Congenital Anomalies, 10.1007/978-1-4899-3109-2_1, (1-672), (1991). Judy Reilly, Edward S. [doi.org]
Jehee FS, Takamori JT, Medeiros PF, Pordeus AC, Latini FR, Bertola DR, Kim CA, Passos-Bueno MR: Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice [bmcresnotes.biomedcentral.com]
- Dysmorphic Face
It is characterized by dysmorphic face, cardiovascular disease, idiopathic hypercalcemia, mental retardation, and an uneven profile of cognitive-linguistic abilities and deficits. [ncbi.nlm.nih.gov]
The characteristic features of WBS include dysmorphic face, cardiovascular disease (especially aortic stenosis), mental retardation, hypercalcemia, growth deficiency, high sociability, and friendly personality. [ijmpo.org]
Williams-Beuren syndrome (WBS) is a rare genetic disease characterized by a typical dysmorphic faces, congenital heart defects, growth deficiency, teeth and skeletal anomalies, inguinal hernia, infantile hypercalcemia, mental retardation, distinct cognitive [scielo.br]
The typical physical WBS phenotype was observed including a characteristic dysmorphic face (elfin-like face) in all the 9 patients and heart defects in eight out of the nine patients. (see Table 1). [journals.plos.org]
- Failure to Thrive
4 months male child presented with failure to thrive. On general examination child had normal O2 saturation with characteristic elfin facies. [ncbi.nlm.nih.gov]
We present an 11-month-old girl child with complaints of constipation, cough, fever, vomiting and growth retardation. On examination, she had facial dysmorphism, hypertension and murmur. [ncbi.nlm.nih.gov]
Pediatric Gastroenterology - Evaluates and offers suggestions for treatment for problems with slow bowel motility, constipation, or gastroesophageal reflux (GER). Pediatric Orthopaedics - Monitors and treats bone and muscle issues. [urmc.rochester.edu]
Adults: 25% have GERD 50% have constipation Hypercalcemia may recur periodically and can contribute to constipation and vomiting Sigmoid diverticulitis occurs with increased frequency and at younger age ( 5,6 Celiac disease may be more common, as in children [vkc.mc.vanderbilt.edu]
Adults: 25% have GERD 50% have constipation Hypercalcemia may recur periodically and can contribute to constipation and vomiting Sigmoid diverticulitis occurs with increased frequency and at younger age ( 30). [iddtoolkit.vkcsites.org]
[…] to nutritionist/gastroenterologist Constipation Consider polyethylene-glycol-electrolyte solution and a good bowel regimen, encouraging fluids, and high fiber foods Chronic abdominal pain Consider gastroesophageal reflux, hiatal hernia, peptic ulcer [clinicaladvisor.com]
The most common oro-facial findings were detected as high palate (87%), diastema (60%), failure to thrive (60%), feeding difficulties (60%), vomiting (47%), macroglossi (47%), microdontia (40%) and frenulum hyperplasia (40%). [ncbi.nlm.nih.gov]
Symptoms Delayed speech that may later turn into strong speaking ability and strong learning by hearing Developmental delay Easily distracted, attention deficit disorder (ADD) Feeding problems including colic, reflux, and vomiting Inward bend of the small [web.archive.org]
Endocrine abnormalities, which include short stature, hypercalcemia (irritability, vomiting, constipation, muscle cramps), diabetes mellitus, and hypothyroidism. GU/Kidney abnormalities, such as dysfunctional voiding and nephrolithiasis. [pedclerk.bsd.uchicago.edu]
Spotting the signs Everyone with Williams syndrome will be be different, but some of the early signs of Williams syndrome in children can include: low birth weight and slow growth excessive vomiting and difficulty feeding constipation trouble sleeping [mencap.org.uk]
- Abdominal Pain
It is important to take diverticulitis into consideration when examining a patient with Williams syndrome presenting with abdominal pain and consider surgical treatment if necessary. [ncbi.nlm.nih.gov]
Young adults continue to experience abdominal pain. Diabetes is another common complication. Children with this condition usually develop diabetes by age of 13. Hearing loss is also common. These medical problems usually cause a premature death. [mentalhelp.net]
GI (1): Colic, difficulty feeding, and intolerance to food textures are common during infancy; at other ages: chronic constipation, gastroesophageal reflux, diverticular disease, abdominal pain of unknown etiology, rectal prolapse, (rarely) celiac disease [unboundmedicine.com]
Chronic abdominal pain is common in adolescents and adults. [brainfacts.org]
Citation: The Journal of Clinical Pharmacology DOI: 10.1002/jcph.1569 Extrapolation of Adult Efficacy to Pediatric Patients With Chemotherapy‐Induced Nausea and Vomiting Authors: Jeremiah D. Momper; M. [journaltocs.ac.uk]
Jaw & Teeth
- Small Teeth
People may also experience dental issues, such as crooked, missing, or small teeth. People with Williams syndrome often have both learning disabilities and cognitive challenges. [beyondceliac.org]
Then the doctor will look for facial features like an upturned nose, wide forehead, and small teeth. An electrocardiogram ( EKG ) or ultrasound can check for heart problems. A bladder and kidney ultrasound can check for urinary tract conditions. [webmd.com]
Dental Children: Missing or small teeth, malocclusion and other dental anomalies are common. [vkc.mc.vanderbilt.edu]
People with Williams syndrome whose NCF1 gene is not deleted have a higher risk of developing hypertension. [web.archive.org]
We report a 38-year-old patient who presented with pulmonary hypertension and right ventricular dysfunction due to pulmonary artery stenoses as a manifestation of Williams syndrome, mimicking chronic thromboembolic pulmonary hypertension. [ncbi.nlm.nih.gov]
- Heart Murmur
We present a case of Williams syndrome that presented to us with heart murmur and cognitive problem. A 5-year-old girl referred to pediatric cardiologist because of heart murmurs. [hindawi.com]
In consultation, facial dysmorphies and heart murmur are detected. There is also low birth weight, failure to thrive, unsuccessful breastfeeding, and gastroesophageal reflux. All these symptoms are strongly suggestive of Williams syndrome. [ncbi.nlm.nih.gov]
During the hospitalization, he presented some facial features such as broad forehead, flat nasal bridge, full cheeks, a wide mouth (Figure 1) and a heart murmur. [ijp.tums.pub]
Dr Riby says there is no pre-natal screening, but often doctors can pick up clues if a young child has heart murmurs, and problems putting on weight. [bbc.com]
- Systolic Murmur
Systolic murmur is similar to valvular aortic stenosis, most prominent at upper right sternal border with radiation into the suprasternal notch and into the neck. [hindawi.com]
In right upper sternal border, a systolic murmur (2-4/6) with radiation to right cervical region was heard. Doppler echocardiography revealed a mild supra valvular aortic stenosis (SVAS), right pulmonary artery stenosis and patent foramen ovale. [ijp.tums.pub]
The murmur associated with it is systolic murmur and is similar in character to valvular aortic stenosis murmur but commonly present at 1st Intercostal space (ICS) on the right. [en.wikipedia.org]
On cardiovascular examination, a moderate systolic murmur ( /4 ) could be heard on the infraclavicular region, bilaterally, and on the left sternal margin irradiating to the dorsum. [scielo.br]
- Joint Limitation
The older children developed progressive joint limitation and hypertonia. Adult patients were handicapped by their developmental disabilities. Hypertension, and gastrointestinal and genitourinary problems occurred frequently. [ncbi.nlm.nih.gov]
Joint limitation or laxity and soft lax skin. Intellectual disability: Most patients have intellectual disability ranging from mild to severe. Some individuals have normal intelligence. [patient.info]
If results of previous evaluations are negative, repeated cardiology evaluation (for arterial stenoses, hypertension) should be performed at puberty Ophthalmologic evaluation for strabismus and hyperopia Orthopedic problems (eg, joint limitation, kyphosis [pediatrics.aappublications.org]
Because of the high prevalence of esotropia in patients with Williams syndrome (72%) compared to the general population (0.1%), we postulate a genetic link between Williams syndrome and the hereditary form of infantile esotropia. [ncbi.nlm.nih.gov]
Therapeutic Aspects Esotropia and amblyopia are treated as appropriate with surgery and patching. Figure 1. [aao.org]
Visual defects may also be present, particularly strabismus, esotropia, nystagmus and abnormal visual processing Recurrent middle ear infections in childhood may have occurred Sensorineural hearing loss may be present. [symptoma.com]
- Periorbital Fullness
Patients may have a broad forehead, bitemporal narrowness, periorbital fullness, stellate/lacy iris pattern, short nose with bulbous nasal tip, wide mouth, full lips and mild micrognathia. [aappublications.org]
The patient showed many of the features such as elfin face, mild mental retardation, swollen eyelids, high palate, epicanthal folds, periorbital fullness, full lower lips, and small mandible. She was also talkative, social, and friendly. [ijmpo.org]
Distinctive facies: Broad forehead, bitemporal narrowing, periorbital fullness. Stellate iris pattern, strabismus. Short nose with broad nasal tip. Long philtrum, wide mouth with thick vermilion of upper and lower lips. [patient.info]
The facial features are distinctive and remain visible into old age, with periorbital fullness, a bulbous nasal tip, a long philtrum, a wide mouth with an everted lower lip, full cheeks, and widely spaced teeth. [ajog.org]
- Friendly Personality
Alexandra is diagnosed with Williams syndrome, a condition known to cause a friendly personality. She has an unconditional love for people, but it is not always returned. [youtube.com]
This is especially important because people with Williams syndrome have a sometimes overly friendly personality and can also have impulse control problems, including sexual impulse control, which may increase their chances of being taken advantage or [thinkgenetic.com]
Beuren presented a similar syndrome with the additional features of peripheral pulmonary stenosis (PPS), dental anomalies and friendly personality. [ijp.tums.pub]
The characteristic features of WBS include dysmorphic face, cardiovascular disease (especially aortic stenosis), mental retardation, hypercalcemia, growth deficiency, high sociability, and friendly personality. [ijmpo.org]
Mental retardation (MR) and the friendly personality occurred in 95% of all patients, ie, in all patients with genomic deletions and in 2 of the 3 patients without deletions. [scielo.br]
Face, Head & Neck
- Thick Lips
The patient had symmetric pulses, a peculiar facies, excessive periorbital subcutaneous cellular tissue, hypertelorism, saddle nose, thick lips, and wide and half-open mouth with separated teeth (fig. 1). [scielo.br]
Such characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). [rarediseases.org]
The typical facial dysmorphisms found in WBS are as follows: high forehead, medial broadening of the eyebrows, periorbital fullness, depressed nasal bridge, malar hypoplasia, thick lips, and long nasolabial philtrum [1, 2, 5]. [hindawi.com]
The clinical genetic examination showed typical WBS facial dysmorphism for all the 9 patients (hypertelorism, short nose with anteverted nostrils, thick lips with everted lower lip, and sagging cheeks) and a cardiac murmur for eight out of the nine patients [journals.plos.org]
Irritability (colic during infancy): Many infants with Williams syndrome have an extended period of colic or irritability. This typically lasts from 4 to 10 months of age, then resolves. It is sometimes attributed to hypercalcemia. [web.archive.org]
Initial pediatric signs are developmental delay and nocturnal irritability. In consultation, facial dysmorphies and heart murmur are detected. [ncbi.nlm.nih.gov]
Eye drops with preservatives may further irritate your eyes. Add more Omega 3s to your diet. Omega 3s, commonly found in fish, can help increase tear and oil production in your eyes. Blink more frequently. [wilsoneyecare.com]
Irritability (colic during infancy) Many infants with Williams syndrome have an extended period of colic or irritability. This typically lasts from 4 to 10 months of age, then resolves. [williams-syndrome.org]
Diagnosis of Williams syndrome is made on the basis of the following :
- Physical and behavioral symptoms
- Physical examination consisting of: Blood pressure, ocular tests, hearing tests, testing for hypotonia in infants
- Bone age assessment
- Glucose tolerance tests
- Cardiovascular tests to check for abnormalities: Electrocardiography (ECG), echocardiography
- Blood tests with particular focus on: Plasma creatine phosphokinase (CPK) levels, serum calcium levels, serum blood urea nitrogen (BUN)
- Thyroid function tests
- Micro-array analysis
- Gene karyotyping
- Targeted mutation analysis
- Polymerase chain reaction (PCR)
- Heterozygosity testing
- Fluorescent in situ hybridization (FISH) test for detection of gene deletion
- Prenatal screening consisting of: Alpha fetoprotein levels (AFP), increased fetal nuchal translucency
Being a genetic defect, Williams syndrome does not have a cure. Symptomatic treatment is, however, possible. Cardiac, visual, gastrointestinal and urinary system and orthopedic abnormalities should be thoroughly assessed and treated accordingly.
The patients should be treated on the basis of their particular tendency for music to placate them and relieve the anxiety and phobias. Surgical interventions for cardiovascular or ocular complications might be required   . Genetic counseling of parents should be done.
Mortality rate due to Williams syndrome is high due to cardiovascular complications. However, most of the patients lead healthy life and live to an old age.
Deletion of a cascade (approximately more than 25) of genes from the long arm of chromosome 7 (q11.23) resulting in gene haplodeficiency is the underlying etiology of Williams syndrome. The gene defect is usually acquired, occurring in the eggs or sperms during their formation. The genes most commonly deleted are:
The incidence of the disease is approximately 1 in 7,500 to 20,000 live births. Most of the cases of the disease are sporadic. The incidence of the disease is equal among the males and females. Symptoms of the disease vary among different races. Chinese populations are more prone to cardiovascular complications whereas Greek populations have low incidence of cardiovascular system abnormalities.
The gene deletions include the deletion of ELN gene that encodes for the protein elastin which is a part of many of the connective tissues including the arterial walls. Loss of elastin results in connective tissue abnormalities in many of the body viscera predominantly in the heart. Pulmonary and aortic valvular stenoses are common manifestations. The loss of elastin manifests in the integumentary system as fullness of the cheeks. Vocal cords are also affected causing hoarseness of voice. Diverticuli are common, especially in the bladder.
Loss of GTF2I, GTF2IRD1 and LIMK1 genes result in visual as well as spatial defects. Deletion of CLIP2 gene results in behavioral changes associated with the disease (eg. irritability) as well as cognitive defects. The deletion or overexpression of NCF1 gene has been linked to the risk of hypertension in people with Williams syndrome. Recent studies have implicated familial inversion polymorphism in the region of chromosome 7 as an underlying cause of Williams syndrome.
Prenatal screening for gene abnormalities is helpful in genetic and anticipatory counseling of the parents and in the management of this condition. Lifelong monitoring of the patients with Williams syndrome should be ensured.
Williams syndrome, also known as Beuren syndrome or Elfin Facies syndrome is a rare disorder that arises due to gene defect. The distinctive features of the disease include characteristic facial features and congenital cardiovascular problems .
Individuals with Williams syndrome are quite sociable and have a cheery demeanor but are unable to form lasting relationships as they are unable to understand the subtleties involved in social interactions. Development delay and cognitive defects are also common in these patients.
Williams syndrome is a gene defect that gives rise to a particular set of symptoms in the patients. The individuals have characteristic facial features including low set nose and wide tip of nose, wide mouth and a broad forehead. The patients have low intelligence levels but have particular fondness for music. Developmental milestones are achieved quite late. Difficulty in coordinated movements like drawing is also faced. Hearing and visual defects are also common. Heart problems are widely observed in these patients.
No cure is available for this disease. The patients can be monitored for heart defects. Such individuals mostly lead a long healthy life but heart abnormalities may become the cause of death.
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