Williams and DiGeorge Syndromes
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Direct answer
Williams syndrome and DiGeorge syndrome are microdeletion syndromes, caused by deletion of 7q11.23 and 22q11.2 respectively. Williams syndrome is classically linked with supravalvular aortic stenosis, elfin facies and a sociable personality, whereas DiGeorge syndrome is linked with conotruncal heart defects, T-cell immunodeficiency and hypocalcaemia from parathyroid hypoplasia. Fluorescence in situ hybridisation or chromosomal microarray confirms the deletion in both conditions.
What you must remember
- Williams deletion: 7q11.23, which includes the elastin gene ELN, the cause of supravalvular aortic stenosis.
- Williams features: elfin facies, a friendly and sociable personality, hyperacusis, mild to moderate intellectual disability and infantile hypercalcaemia.
- DiGeorge deletion: 22q11.2, which also causes velocardiofacial syndrome and CATCH-22 features.
- CATCH-22 mnemonic: cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcaemia on a 22q11 deletion.
- Cardiac defects: conotruncal lesions such as tetralogy of Fallot, truncus arteriosus and interrupted aortic arch type B in DiGeorge syndrome.
- Immunity and calcium: thymic hypoplasia causes T-cell deficiency, and parathyroid hypoplasia causes hypocalcaemia with neonatal tetany.
- Psychiatric risk: people with the 22q11 deletion have a higher risk of psychiatric illness, including schizophrenia-spectrum disorders.
A stepwise approach to a neonate with a heart defect and abnormal calcium
A neonate with a conotruncal defect and a seizure from low calcium needs an early, structured workup. The steps below separate the two syndromes within the first days of life.
- Check the calcium first. Neonatal hypocalcaemia with tetany points to DiGeorge syndrome, whereas infantile hypercalcaemia suggests Williams syndrome.
- Examine the heart and face. A conotruncal defect with dysmorphic features favours the 22q11 deletion, while supravalvular aortic stenosis with an elfin face and stellate iris pattern favours Williams syndrome.
- Assess immunity. A low T-cell count with a small thymic shadow suggests thymic hypoplasia, and this affects the choice of vaccines.
- Confirm the deletion. Fluorescence in situ hybridisation tests for the 22q11.2 and 7q11.23 deletions, and microarray detects other copy-number changes.
- Treat the complications. Give calcium and vitamin D for hypocalcaemia, manage the cardiac lesion, and defer live vaccines until immune status is known.
- Plan long-term follow-up. Review learning, speech and renal function, and in DiGeorge syndrome also watch for endocrine and psychiatric problems through adolescence.
Where the exam tries to catch you
Three errors recur on this topic.
- Trap: expecting hypocalcaemia in Williams syndrome Correct: Williams syndrome causes infantile hypercalcaemia, whereas DiGeorge syndrome causes hypocalcaemia from parathyroid hypoplasia.
- Trap: linking immune deficiency with Williams syndrome Correct: T-cell immunodeficiency belongs to DiGeorge syndrome, because thymic hypoplasia is part of the 22q11 phenotype.
- Trap: attributing supravalvular aortic stenosis to DiGeorge syndrome Correct: supravalvular aortic stenosis points to Williams syndrome, while DiGeorge syndrome causes conotruncal lesions such as tetralogy of Fallot and truncus arteriosus.
Frequently asked questions
Which cardiac defects are typical of DiGeorge syndrome?
Conotruncal defects are typical of DiGeorge syndrome, and the commonest are tetralogy of Fallot, truncus arteriosus and interrupted aortic arch type B. These lesions, together with dysmorphic facies, are important clues on examination and echocardiography. Cardiac anomalies therefore prompt testing for the 22q11.2 deletion.
Why does infantile hypercalcaemia occur in Williams syndrome?
Infantile hypercalcaemia in Williams syndrome is attributed to increased sensitivity to vitamin D, which raises intestinal calcium absorption. It often presents in the first year with poor feeding and irritability. Affected infants are managed by restricting calcium and vitamin D intake, under specialist supervision.
Why are live vaccines withheld in suspected DiGeorge syndrome?
Live vaccines are withheld in suspected DiGeorge syndrome because thymic hypoplasia can cause severe T-cell deficiency, and a live attenuated vaccine may then cause disseminated infection. Immune status, usually assessed with T-cell counts and immunoglobulin levels, is checked first. Inactivated vaccines are generally considered safer, and the decision is made with a specialist.
Which test confirms Williams or DiGeorge syndrome?
Fluorescence in situ hybridisation confirms the deletion in Williams syndrome at 7q11.23 and in DiGeorge syndrome at 22q11.2. Chromosomal microarray detects these microdeletions along with other copy-number changes in a single test. Standard karyotype may miss such small deletions, so a targeted test is needed.