Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome

Abstract

Latent hypoparathyroidism (LHP), the inability to increase midmolecular parathyroid hormone levels appropriately during a hypocalcemic challenge, was reported previously in an asymptomatic woman with tetralogy of Fallot. This women's fourth child died with DiGeorge anomaly. Seven years later, we restudied the index patient with LHP and evaluated three generations of her family for parathyroid dysfunction, cardiac abnormalities, and del 22(q11). Deletions were found in six relatives, three with conotruncal cardiac defects and three with a structurally normal heart. We found significant transgenerational noncardiac phenotypic variability, including learning difficulties, dysmorphic facial appearance, and psychiatric illness. A spectrum of parathyroid gland dysfunction associated with the del 22(q11) was seen, ranging from hypocalcemic hypoparathyroidism to normocalcemia with abnormally low basal intact parathyroid hormone (iPTH) levels. In addition, LHP found in the index patient 7 years ago had evolved to frank hypocalcemic hypoparathyroidism. In this family, which is the largest family with 22q11 deletions studied to date, parathyroid gland dysfunction evolved over time. We suggest that the calcium parathyroid hormone axis of unrelated patients with del 22(q11) be followed closely for the development of hypocalcemic hypoparathyroidism.

An Adult Case of 22q11.2 Deletion Syndrome Diagnosed in a 36-year-old Woman with Hypocalcemia Caused by Hypoparathyroidism and Hashimoto's Thyroiditis

“…Although it is unclear why symptomatic hypocalcemia appeared in an adult in our case, a spectrum of parathyroid gland dysfunctions have previously been reported to be associated with this syndrome (2,13,14) and may develop gradually with individual differences. Alternatively, a lateonset appearance of symptomatic hypocalcemia can be caused by hypocalcemic stress (15,16).…”

22q11 deletion syndrome: a genetic subtype of schizophrenia

“…Developmental medical history may include neonatal seizures due to hypocalcemia that is secondary to hypoparathyroidism (Cuneo et al 1997), or repeated infections, due to defective cellular immunity. These features, typical of DGS, occur most often in infants and children and are usually transient Lindsay et al 1995b;Ravnan et al 1996).…”

“…First, patients with 22qDS will benefit from a consultation with a medical geneticist. Ongoing monitoring for onset of associated psychiatric illness, hypocalcemia, and hypothyroidism, that may occur in later years, has been recommended (Bassett et al 1998;Cuneo et al 1997). These are treatable conditions and patients would benefit from early diagnosis and treatment that could lead to improved long-term outcomes.…”

Bone density and metabolism in subjects with microdeletion of chromosome 22q11 (del22q11)

“…Hypocalcaemia is a frequent manifestation in subjects with 22q11DS, particularly in patients of neonatal age, although it may also be observed later in life (20). This disorder is present in 49-60% of patients with a confirmed del22q11 (4), and patients with the phenotypic characteristics of the DiGeorge anomaly are more likely to have clinical evidence of hypocalcaemia (70%) than patients with VCFS (13-22%) (21).…”

“…This mild or transient hypocalcaemia may frequently be missed because it is probably asymptomatic, and a systematic screening is required for its detection (20). Commonly, however, with an increase in dietary calcium intake, the remaining parathyroid activity supplies sufficient PTH to meet metabolic demands, even if a recurrence of hypoparathyroidism may be precipitated during the periods of increased metabolic demand (18).…”