Delayed diagnosis of 22q11 deletion syndrome due to late onset hypocalcemia in a 11-year-old girl with imperforated anus

Abstract

Neonatal hypocalcemia and congenital heart defects has been known as the first clinical manifestation of the chromosome 22q11.2 deletion syndrome (22q11DS). However, because of its wide clinical spectrum, diagnosis of 22q11DS can be delayed in children without classic symptoms. We report the case of a girl with the history of imperforate anus but without neonatal hypocalcemia or major cardiac anomaly, who was diagnosed for 22q11DS at the age of 11 after the onset of overt hypocalcemia. She was born uneventfully from phenotypically normal Korean parents. Imperforate anus and partial cleft palate were found at birth, which were surgically repaired thereafter. There was no history of neonatal hypocalcemia, and karyotyping by GTG banding was normal. At the age of 11, hypocalcemia (serum calcium, 5.0 mg/dL) and decreased parathyroid hormone level (10.8 pg/mL) was noted when she visited our Emergency Department for fever and vomiting. The 22q11DS was suspected because of her mild mental retardation and velopharyngeal insufficiency, and a microdeletion on chromosome 22q11.2 was confirmed by fluorescence in situ hybridization. The 22q11DS should be considered in the differential diagnosis of hypocalcemia at any age because of its wide clinical spectrum.

Genetic Screening in a Large Chinese Cohort of Childhood Onset Hypoparathyroidism by Next-Generation Sequencing Combined with TBX1-MLPA

“…They were all eventually diagnosed by TBX1 ‐MLPA screening, suggesting the necessity of TBX1 screening in pediatric HP patients. Previous studies also demonstrated that infants without evident facial abnormalities and intellectual problems may be undiagnosed . Not all, but only six of nine patients with an AIRE mutation were found to have classical features of APS1, such as Addison's disease, chronic candidiasis, chronic diarrhoea, and enamel hypoplasia.…”

“…Previous studies also demonstrated that infants without evident facial abnormalities and intellectual problems may be undiagnosed. (20)(21)(22) Not all, but only six of nine patients with an AIRE mutation were found to have classical features of APS1, such as Addison's disease, chronic candidiasis, chronic diarrhoea, and enamel hypoplasia. In another three patients with HP as the main presentation, no other phenotypes related to APS1 were found until their last visit.…”

“…(7,33,34) However, due to a lack of awareness of physicians and varied or untypical presentations of the disorder, patients with DGS without typical clinical features may be undiagnosed or misdiagnosed. (20)(21)(22) This suggests that DGS should always be screened for in childhood onset patients not only with clinically suspected DGS, but also with so-called "isolated HP." According to our results and previous reports, gene defects in DGS1 are mainly entire gene deletions in chromosome 22, and the TBX1 gene plays a major role.…”

Chromosome 22q11.21 and 11p15.4 microdeletions confirmed by high‐throughput sequencing analysis in one patient with asymmetric cry syndrome: Case report and review of the literature

“…In our case, serum calcium level was normal (2.3 mmol/L, reference rage, 2.1‐2.7 mmol/L), and no hypocalcemic symptoms of seizures, tremors, or tetany were observed on admission, which ruled out the possibility of hypocalcemia due to hypoparathyroidism. Although hypocalcemia may not be present during the neonatal period, 8 studies have shown that it can occur at any time during childhood, 4,9 adolescence, 10 and even in adulthood 11,12 . This is likely due to the recurrence of hypoparathyroidism precipitated by increased metabolic demand and acute illness during pregnancy, surgery, infection, or any physiologic stress conditions.…”

Late diagnosed DiGeorge syndrome in a 44-year-old female: a rare cause for recurrent syncopes in adulthood—a case report

“…In one study where 70/228 patients were late-diagnosed, the most common first presentation in hospital was hypocalcaemic seizure. 4 Evaluation of survival probability in 309 adults with DiGeorge syndrome demonstrated that severe congenital heart disease (CHD) was a significant predictor for mortality (survival probability to age 45 years was 72% in those with CHD vs. 95% in those who had no major CHD; P < 0.0001). 5 The cardiovascular system is involved in 82% of patients with DiGeorge sydnrome, 6 with symptomatic heart failure in 75%.…”