Author: Adam Md Kamal
Editor: Dr. Suneet Sood
Narrators: Adam Md Kamal
Picture this: it’s a busy morning in the emergency department, as usual. You, a junior houseman, have just finished following your senior doctors for rounds. Just as you’re about to rest, your supervising medical officer approaches, looking visibly flustered. Dr. Lee is usually very friendly to you, but today he looks like he’s in a rush. “He must be very busy”, you think to yourself. Just as you try to smile to Dr. Lee, with a serious expression, he tells you “Hey, I have an urgent case that I need to attend to now. Like right now. There’s a child over there, just admitted, the mother looks distressed. Talk to them, get a history. OK?”
“Sure, doctor. Will do”, you reply. Not that you had a choice.
So you go to the mother and child and begin talking to the mother, who introduces herself as Maryam. You begin discussing about her 7-month old son, Ali.
“See Ali here, he’s always sick” she says, “always coughing, he keeps getting sick”. “How sick?” you ask. “It’s always like a flu-kind of thing; sneezing and coughing but not vomiting or pooping problems. He has 3 older siblings, and I know, I just know, that Ali seems to be a lot weaker than them.” “Hmm…that sounds distressing. So you think he falls sick easily, at least, compared to his siblings?” you ask. “Yes I’m sure of it” she replies. Now your past medical knowledge starts conjuring ideas in your mind. “Maybe some sort of immunosuppressed state? Perhaps leukocytopenia?” you think to yourself “Perhaps, pancytopenia?” You continue asking Maryam “what other problems do you feel Ali is experiencing?”
She continues, “Yes, today, I noticed he’s very stiff, like he is all tense up for some reason. I noticed this when I was trying to breastfeed him. The worst part is, I noticed he wasn’t suckling, like he’s too tense to suckle. THAT’s what worried me the most. That’s when I brought him here, to the hospital”.
Now, the history seems clearer: Frequent infections, poor feeding and some sort of generalized spasm. When you approached the mother and child, all your attention was towards the mother, but now you direct it towards the child. You take a good look at baby Ali and notice several key features. First: the hands appear to be in a sort of shape. You’ve seen this before from your previous rotations. Then you remember it, yes, it’s called a carpopedal spasm (3), but you forgot what this indicates. And you also notice that Ali is generally tensed up, just as Maryam described. But in addition to these, you notice several other more striking features: Ali’s face appears dysmorphic, but it doesn’t quite look like Down’s syndrome facies (4). Yet, his head appears long, his jaw appears small and teeth are also unusually small (5). Most noticeably, he has a cleft palate (5). You ask Maryam and she confirms that indeed, he’s had a cleft palate since birth.
You proceed to conduct a thorough physical examination and find peripheral cyanosis (5) and URTI symptoms of sneezing in addition to the previous abnormal facies and cleft palate. Other systems are unremarkable. So you stand there pondering as Maryam nurses Ali, pondering for a diagnosis. Sounds a lot like a chromosomal abnormality like Down syndrome (4), but something doesn’t add up: the spasms. They are not very typical of Down Syndrome children. Then, you take peak at Ali’s lab results.
After a good look at those results, you summarize the findings to yourself. Blood results shows low white cell count, but other blood cell counts are normal. Leukocytopenia, which you anticipated earlier based on the frequent infections (5). But surprisingly amongst the normal results, you notice one striking result, low serum calcium. You now suspect the hypocalcemia to be the cause of Ali’s spasms. To confirm your suspicions, you tap on the posterior end of Ali’s mandible. Sure enough, a positive Chvostek’s sign indicating hypocalcemia (3). At this point you notice Ali has been stabilized adequately by the staff, the nurses don’t seemed concerned with him and attend to other patients. “At least he’s stable”, you think.
Going back to the results, you summarize your findings as concisely as possible: hypocalcemia, leukocytopenia, cleft palate, abnormal facies. You think about this for a very long time. The longer you think, the more you find yourself giving up on reaching a diagnosis. Frustration sets in.
Just when you were about to capitulate and all hope seems lost, here comes Dr. Lee again. This time he looks a lot happier & a lot like his usual self. With a large grin on his face, he asks you, “So, how’s things? Diagnosis?”. You relay all your findings from history to investigations to Dr. Lee who listens intently. Then, he scratches his chin, pauses and casually says, “DiGeorge Syndrome”.
“DiGeorge syndrome? What’s that?” you ask. ”Well, see here its quite simple actually, if you remember your embryology. You do remember your embryology, don’t you?” he asks cynically. You remain silent and smile.
So, he goes on. “Anyway, just recall that there are pharyngeal pouches which develop into other structures around the neck (6). Specifically, let’s talk about the pharyngeal pouches 3 & 4. These will eventually lead to the formation of the thymus, parathyroid gland, and part of the palate and heart by conotruncal development which separates the pulmonary artery from the aorta (6). So in DiGeorge syndrome, there’s a chromosomal defect in the location 22q11 (5), which carries genes for the development of the pharyngeal pouches 3 & 4 (7). Therefore, the results are as you expect: aplasia of the thymus leads to leukocytopenia, defective parathyroid gland leads to hypocalcemia, defective conotruncal development leads to congenital heart disease, (a lot of types but we aren’t sure which one yet in Ali’s case) and of course the cleft palate (7). Common sense isn’t it?”.
Listening to Dr. Lee’s explanation, you say, “Wow, that was a really good explanation Doctor. So basically, all the symptoms, hypocalcemia, leukocytopenia, cyanosis and cleft palate all relate to the defective embryological development of pharyngeal pouches 3 & 4? (5)(7)” you ask. “Yes, that is exactly right. In case you want to remember this disease well you can remember the mnemonic CATCH-22:
C for Cardiac abnormalities
A for Abnormal facies
T for Thymic aplasia
C for Cleft palate
H for Hypocalcemia
& 22 for chromosome 22q11 defect.
Memorize this mnemonic and you’ll be alright in case you see another DiGeorge syndrome patient.” Dr. Lee says.
You stand there, trying to digest everything Dr. Lee said for a moment. He interrupts the silence, “Anyway, that’s enough lecturing for one day, I’m not paid for it anyway J ……help me prop up the child one moment, I want to examine the child.” You oblige, continuing your work despite the fatigue and information overload.
- UCSD’s Practical Guide to Clinical Medicine [Internet]. [cited 2020 Jan 30]. Available from: https://meded.ucsd.edu/clinicalmed/ros.htm
- Phillips KA, Ospina NS. Physicians Interrupting Patients. JAMA. 2017 Jul 4;318(1):93–4.
- Hypocalcemia Clinical Presentation: History, Physical Examination [Internet]. [cited 2020 Jan 30]. Available from: https://emedicine.medscape.com/article/241893-clinical
- Down Syndrome: Practice Essentials, Background, Pathophysiology [Internet]. [cited 2020 Jan 30]. Available from: https://emedicine.medscape.com/article/943216-overview
- DiGeorge Syndrome: Practice Essentials, Background, Pathophysiology. 2019 Nov 12 [cited 2020 Jan 30]; Available from: https://emedicine.medscape.com/article/886526-overview
- Duke Embryology – Craniofacial Development [Internet]. [cited 2020 Jan 30]. Available from: https://web.duke.edu/anatomy/embryology/craniofacial/craniofacial.html
- DiGeorge Syndrome: Practice Essentials, Background, Pathophysiology. 2019 Nov 12 [cited 2020 Jan 30]; Available from: https://emedicine.medscape.com/article/886526-overview#a3