Dr Laura Johnston, Dr Claire Alcorn, Dr Danielle Leemon, Dr Shilpa Shah 

On a particularly busy evening shift, Laura a paediatric ST3 doctor was asked to review a newborn baby boy called Will.

Will was born to a 26 year old first time mum with no past medical problems, at 37 weeks, after labour was induced due to small size and static growth. No abnormalities had been seen on antenatal scans. The delivery was uneventful and APGAR scores were 9 at 1 and 5 minutes. 

The baby boy plotted on the 0.4th-2nd centile for weight, length and head circumference. He had some unusual facial features and a loud heart murmur. 

The FY2 doctor shadowing Laura asked her,

What could be the cause of these findings? Do they count as a ‘birth defect’ and are they genetic? 

An abnormality which is present at birth is termed a ‘birth defect’ – but some birth defects may not become obvious until some time later. Around 3% of newborn babies will have a birth defect. 

They can be classified as 

  • Malformation: a structural defect that results in abnormal formation of a tissue or organ (e.g. polydactyly, extra fingers or toes) 
  • Dysplasia: abnormal organisation of cells into tissues at organ level – e.g. spina bifida, where there is incomplete closure of the membranes around the spinal cord
  • Deformation: where the shape or structure of an organ or body part has been altered later in development (e.g. Potter syndrome secondary to oligohydramnios)
  • Disruption: the breakdown of a normally formed structure. 

Birth defects can be genetic, developmental, environmental or epigenetic.

  • Genetic – an abnormality in the total number of chromosomes (for example Trisomy 21) insertion or deletion of genetic material, (e.g. DiGeorge syndrome – 22q11 deletion) or a single gene condition (such as Cystic Fibrosis where two copies of the recessive CTFR gene are expressed).
  • Developmental – a problem with how a body part or body system works or functions. Genetics are normal, but depending on the defect there could be reduced function. Examples include isolated cleft lip, heart defect, and spina bifida.
  • Environmental – something about the environment the baby has developed in has affected their development. Things like drinking alcohol or taking drugs in pregnancy, smoking, or having an underlying medical condition like diabetes can all affect foetal development. 
  • Epigenetic – These are changes in gene expression that are not caused by changes in the DNA sequence. Examples are prenatal and early postnatal environmental influences on adult health and behaviour. 

Laura saw the following facial features- broad forehead, an unusual ‘star like’ pattern in the irises, epicanthic folds, a long philtrum and a small lower jaw

stellate (star like) iris pattern

On cardiovascular assessment his vitals (including blood pressure and pre and post ductal saturations) were normal. He had a loud  systolic murmur in the aortic area. 

She made a mental note of the constellation of findings and wondered about Williams Syndrome. Her colleague taking over the shift was Danielle, an ST8 doctor. Together they explained what would happen next to Will’s parents. 

Why did they consider Williams Syndrome in this case? What comes next? 

Williams Syndrome is caused by a microdeletion of 7q11.23, which includes the elastin gene. It is inherited in an autosomal dominant manner, but the majority of cases are new mutations.

Williams Syndrome on Twitter: "… "

In old textbooks you might see the facial features of people with Williams syndrome described as ‘elfin’ but comparing our patients’ appearances to mythical woodland beings is not something we should ever do! It is better to describe the features as they appear: a wide mouth, with a pronounced bottom lip; an upturned nose with flattened bridge; slightly high, rounded cheeks; irregular and/or widely-spaced teeth; starburst eyes; and a squint. 

Children with Williams syndrome are often short in stature. Cardiovascular abnormalities are common – the usual ones being supravalvular aortic stenosis and branch/peripheral pulmonary stenosis.  

Hypercalcaemia, hypothyroidism, type II diabetes and early puberty are also associated with Williams Syndrome. People with William’s Syndrome tend to have particular personality traits like being very talkative and uninhibited, and are often excessively friendly towards adults. They can have attention deficit disorders and mild to moderate learning difficulties.

A diagnosis of Williams syndrome was confirmed on genetic testing and a supra aortic valvular stenosis was diagnosed by cardiologists. Other tests included a normal electrolyte and bone profile.

Will was followed up by general and community paediatrics, cardiology, dietetics and parents were referred to genetics for counselling. For a year or so, things seemed to be going well with only some minor developmental delay noted. 


One evening (at the age of 13 months) Will presented to the emergency department with irritability and constipation. Claire, an ST6 doctor assessed that he appeared dehydrated. She ran a set of bloods and found his calcium level was 3.15 mmol/L and urea was slightly high. 

Why does Will have hypercalcaemia? How is it managed? 

Hypercalcemia has been reported in up to 43% of individuals with Williams syndrome. It tends to affect them particularly as young infants, and again in adolescence/adulthood. Symptoms include irritability, dehydration and reduced oral intake (but it can also be asymptomatic, and picked up by testing urine calcium). 

It’s important to remember that nephrocalcinosis is a common complication, so do a renal ultrasound and keep an eye on renal function blood tests when you are treating a Williams syndrome patient with hypercalcaemia!

Get the dieticians and endocrinologists involved  – reduced calcium intake is recommended but given the risk of decreased bone density in later life, restricting calcium and vitamin D below the recommended daily intake levels should be avoided for those with a normal calcium level. 

Most people with Williams syndrome can maintain normal calcium and vitamin D levels through a healthy diet. Children and adults with overly restrictive diets should be under the care of a dietician.

Will was treated with hyper hydration therapy and diuretics, but the hypercalcaemia didn’t correct. Other tests including vitamin D and parathormone levels were normal. He was started on a low calcium diet under dietetic input. 

Despite this the calcium level remained high, so the endocrinology team got involved. Will was given Pamidronate therapy and responded well to this. Over the following year, the dietician helped to introduce more calcium into Will’s diet, and his calcium was monitored regularly. 

What follow up should there be?  

You may find this American academy of Pediatrics publication useful. Children with Williams Syndrome can have complex needs and they are all different so a team approach is best! Any or all of the following might be needed – developmental team, geneticist, dietician, dentist, ENT, orthopaedics, cardiology, neurology, endocrinology, nephrology…

Here is a summary: 

Specific area of surveillance At diagnosis 0-12 months1-5 years6-12 years13-18 yearsAdult
Plot growth (weight, height, head circumference)  on specific Williams syndrome growth chart YesYes Each visit Each visit Each visit 
Blood pressureYesYesEach visit Each visitEach visitEach visit 
Spinal problems: Screen for kyphosis, scoliosis, lordosisYesYearlyYearlyYearlyYearlyYearly
Check for inguinal herniaYesEach visitYearlyYearly YearlyYearly
Eye test Yes YearlyYearlyYearlyYearlyYearly (Also cataract) 
Hearing testYesYearlyYearlyYearlyYearly Yearly
Dental check upYes6 monthly6 monthly4 monthly 4 monthly 
Paediatric cardiologyYesEvery 3 monthsYearly2 yearly2 yearly2 yearly
Blood test – Serum calcium Yes4 monthly4-6 monthly till 2 years2 yearly2 yearly2 yearly 
Renal ultrasound with DopplerYesEvery 10 yearsEvery 10 yearsEvery 10 years 
Blood test – Thyroid functionYesYesYearly till age 3 years2 yearly2 yearly2 yearly 
Fasting blood sugar (then Glucose tolerance test if abnormal) YearlyYearly 

Authors: Dr Laura Johnston Paediatric ST3, Dr Claire Alcorn Paediatric ST6, Dr Danielle Leemon Paediatric ST8, Dr Shilpa Shah Paediatric Consultant. Craigavon Hospital, Northern Ireland 

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