Presentation in adulthood is rare, but should be considered when dealing with cases of hypoparathyroid hypocalcemia.
Introduction:
DiGeorge Syndrome has an estimated prevalence of 1 in 4,000-6,000 live births, making it one of the most common genetic disorders \cite{Devriendt1998}.
The syndrome is due to a microdeletion of chromosome 22q11.2, and less commonly 10p13. Deletion can be inherited but more typically occurs as a de novo event. If a parent has a deletion, risk to each child is 50%. However, 22q11.2 deletions have been found in only 28% of parents of the affected people \cite{Ryan1997}. The syndrome is associated with failure of development of the third and fourth branchial pouches \cite{Robinson1975}. It's been suggested that there is a failure of or aberrant migration of the neural crest during the fourth week of embryogenesis \cite{Mølsted2010}.
The syndrome can be classified as partial or complete. Complete DGS describes patients with DGS who are athymic or have no circulating T cells (less than 1% of all DGS cases). Those with partial DGS have thymic hypoplasia, evidenced by presence of circulating T cells \cite{Müller1989}.
Case Report:
Patient is a 30-year-old female presented to the hospital with worsening fatigue, malaise, facial/perioral/tongue numbness, and a tingling sensation all over her body. The patient said she's been experiencing the weakness and numbness, on and off, for the past several years. Minor cramps of the hands and legs are also associated with the numbness.
Past medical history included congenital heart disease (coarctation of aorta, VSD), vitiligo, neuropathic pain, bipolar disorder, anxiety, and learning disabilities. Patient has been vitamin D deficient since 2017. She had a prescription for ergocalciferol (vitamin D2) 50,000 units, but has been out of her vitamins for two months. This was her first hospitalization related to fatigue and numbness.
On physical exam, there was mild facial dysmorphism including a long face and bulbous nose. She displayed a positive Chovstek's and Trousseau's sign.
Laboratory values revealed a serum calcium level of 6.3 mg/dL, ionized calcium of 3.4 mg/dL, phosphorus 3.4 mg/dL, vitamin D of 28.9 ng/mL, and PTH of 44.2 pg/mL. The expected rise in PTH due to vitamin D deficiency was not present, suggesting a possible diagnosis of hypoparathyroidism. The hemoglobin was 10.4, white blood cell count 2.98, and platelets 120,000. A chronic pancytopenia of at least 4 years was noted per chart review. Negative ANA, HIV, Hepatitis panel, EBV. Zinc and copper levels were within normal limits. Liver enzymes were slightly elevated with an AST of 53 and ALT of 112. An abdominal ultrasound revealed hepatic steatosis. FISH analysis detected a deletion of TBX1 (22q11.21), supporting a diagnosis of velocardiofacial syndrome (VCFS).
Literature Review
- Microdeletion of 22q11.2 has been found in 90% of people with the full DGS phenotype, in 70% of people with VCFS features, and in 15% of people with isolated conotruncal cardiac defects. \cite{Driscoll1993}
- Clinically significant immunological problems are very uncommon. Nine percent of patients had cleft palate and 32% had velopharyngeal insufficiency, 60% of patients were hypocalcaemic, 75% of patients had cardiac problems, and 36% of patients who had abdominal ultrasound had a renal abnormality. Sixty-two percent of surviving patients were developmentally normal or had only mild learning problems. The majority of patients were constitutionally small, with 36% of patients below the 3rd centile for either height or weight parameters. \cite{Ryan1997}
- Characteristic facial findings include hypertelorism, micrognathia, a short philtrum with a fish-mouthed appearance, small hooded eyes, antimongoloid slant, telecanthus with short palpebral fissures, low-set ears often with defective pinnae, and submucous cleft palate \cite{Butts2009}.
- Psychopathology is common in 22q11DS, with an
Other Documented Case Studies:
- 25 year old female presented with auditory hallucinations with a PMH VSD, cleft palate, intellectual disability found to have deletion of 22q11.2 \cite{Tamune2017}.
- Two patients found with partial Digeorge syndrome present with attention disorder and learning difficulties \cite{Hacıhamdioğlu2011},
- A 34-year old male presented with hypocalcemia-induced seizures found to have a deletion f 22q11.2 \cite{Zammit2013}.
- A 39 year-old woman was diagnosed with DiGeorge's syndrome based on newly diagnosed hypocalcaemia, appearance and history \cite{Hoffmann2000}.
- 21-year-old African American woman who presented with psychotic features and the incidental finding of basal ganglia calcifications on computed tomography (CT) scan of the head found to have DiGeorge's syndrome \cite{Rizvi2018}.
- \cite{van2009}