DiGeorge syndrome

A 10-day-old boy is brought to the emergency department for evaluation of generalized tonic-clonic seizures. The parents note recurrent upper and lower extremity muscle spasms. He has had no fever, cough, or runny nose. The patient was born full term via an uncomplicated pregnancy and normal vaginal delivery. Family history is unremarkable. Physical examination demonstrates a neonate with rhythmic jerking movements of the upper and lower of extremities bilaterally. The anterior fontanelle is open, pupils are reactive to light, and fundi are normal. Facial examination reveals a small lower jaw, low set ears, and a submucosal cleft palate. Lungs are clear to auscultation bilaterally. Cardiac auscultation reveals a harsh holosystolic murmur at the left lower sternal border. Chest x-ray demonstrates decreased soft tissue attenuation in the right anterior mediastinum. Which of the following immunologic derrangements is most likely to be observed in this patient?

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2024

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2021

DiGeorge syndrome p. 96, 638

Hypocalcemia p. 335, 609

DiGeorge syndrome p. 638

Velocardiofacial syndrome p. 63

The name DiGeorge syndrome isn’t the most descriptive name, which is why it’s often also referred to as 22q11.2 deletion syndrome, which is actually pretty descriptive, and describes a condition in which a small portion of chromosome 22 is deleted, which causes a bunch of developmental abnormalities and complications.

Alright so our chromosomes are composed of genes, right?

Which are essentially instructions for everything from development to day-to-day survival, and these genes are spread out across 23 pairs of chromosomes.

22q11.2 is like an address, so 22 stands for chromosome 22, with q designating the long arm of the chromosome, then it’s on region 1, band 1, and sub-band 2.

This portion of dna, 22q11.2, spans about 30 genes and 1.5 to 3 million base pairs, which classifies it as a microdeletion since it’s less than 5 million base pairs.

Even though this region is relatively small, it encodes for some really important genes, one of which is the TBX1 gene, which is thought to play a big role in the disease.

The TBX1 gene is involved in normal development of the pharyngeal pouches, specifically pouch 3 and 4, which are fetal structures that develop into parts of the head and neck.

The third pharyngeal pouch goes on to develop into the thymus and the inferior parathyroid gland, the fourth pouch goes on to develop into the superior parathyroid gland.

So with a 22q11.2 deletion and therefore no TBX1 gene, the thymus and parathyroid gland both end up underdeveloped, called hypoplasia.

T lymphocytes or T cells are immune cells that’re super important for the adaptive immune response, and are produced in the bone marrow but mature in the thymus.

If someone has thymic hypoplasia and thymic dysfunction, the T cells don’t mature, and so these people often have a deficiency in mature T cells.

It turns out, though, that most people with DiGeorge syndrome have mild to moderate thymic dysfunction, called partial DiGeorge syndrome, which means that the immunodeficiency isn’t life-threatening.

DiGeorge syndrome

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