Hypoparathyroidism and 22q11 deletion syndrome

The 22q11 syndrome has a minimum prevalence of 13 per 100 000 live births, making it the most frequent contiguous gene deletion syndrome in humans and second only to trisomy 21 as a chromosomal cause of significant congenital heart disease. ¹ Transient neonatal hypocalcaemia is a well recognised feature of individuals with 22q11 deletion syndrome. This syndrome includes DiGeorge syndrome, ² velocardiofacial syndrome, ³ and conotruncal anomaly face syndrome. ⁴

Hypoparathyroidism is classically a transient feature in the neonatal period and more a characteristic of the DiGeorge syndrome subgroup of 22q11 deletion syndrome. Ryan and colleagues ⁵ reported hypocalcaemia in 60% of subjects with 22q11 deletion syndrome, mostly in the neonatal period, but some in childhood; one patient was diagnosed aged 18 years. The natural history of hypocalcaemia remains poorly understood or defined. It has been shown to be both latent ⁶ and overt ⁷ in children and adolescents with 22q11 deletion syndrome. Adachi and colleagues, ⁸ in reviewing their population of patients with hypoparathyroidism, found 10 of 14 children to have 22q11 microdeletion with an age of diagnosis of hypoparathyroidism between 9 days and 13 years.

The population of individuals with 22q11 deletion syndrome are cared for by many different specialists because of their variable phenotype. We hypothesised that in a population of patients in South Wales with known 22q11 deletion syndrome, it was probable that some may have undiagnosed hypoparathyroidism. The complications of chronic hypocalcaemia due to hypoparathyroidism may include lethargy, irritability, emotional lability, convulsions, cataracts, dental abnormalities, and calcification of basal ganglia and subcutaneous tissues. The treatment of hypoparathyroidism is relatively simple and can bring about profound clinical improvement. ⁹ The aim of our study, therefore, was to investigate for hypoparathyroidism in a population of individuals outside the neonatal period known to have 22q11 deletion syndrome.

SUBJECTS AND METHODS

Patients known to have the 22q11 microdeletion from FISH (fluorescent in situ hybridisation) studies were eligible for recruitment into the study. Patients with the 22q11 microdeletion were identified from registers held by the Institute of Medical Genetics, and the Paediatric Cardiology and Endocrine Services.

Investigation consisted of a detailed clinical history enquiring into symptoms of hypocalcaemia, blood sampling for measurements of serum concentrations of calcium (normal range for children...