CHARGE syndrome or Hall-Hittner syndrome is a pleiotropic disorder, in which the name is derived from the abbreviation epitomizing its six clinical criteria: ocular coloboma, cardiac defects, choanal atresia, growth or developmental retardation, genital hypoplasia, and ear anomalies or deafness. Wolff-Parkinson-White syndrome is the most frequent pattern of ventricular pre-excitation. Patent ductus arteriosus is one of the most frequent congenital heart diseases due to failure of closure of the ductus arteriosus within 72 hours of birth. CHARGE syndrome, Wolff-Parkinson-White syndrome, and patent ductus arteriosus are so difficult to be present in a single entity.

1. CHARGE syndrome hallmarked with Wolff-Parkinson-
White syndrome and patent ductus arteriosus; 20 years post-
repairing; an extreme combination
(A case report)
Dr. Yasser Mohammed Hassanain Elsayed
Clinical Research and Clinical Trials Summit (CRCT-2021)
December 27-28, 2021
Singapore

2. CHARGE syndrome hallmarked with Wolff-
Parkinson-White syndrome and patent ductus
arteriosus; 20 years post-repairing; an extreme
combination
(A case report)
Dr. Yasser Mohammed Hassanain Elsayed
Researcher and author
Critical Care Medicine
Egyptian Ministry of Health (MOH)
MB Bch, PGDip Cardiology (Middlesex University, RILA)

3. My greetings

4. Learning objectives
• The starting point
• The abstract
• Vocabulary or keys for the current case report
• Discovery history
• Identification of keys of the case
• Case presentation
• Treatment
• Discussion
• Conclusion and Recommendations

5. The starting point
(Introduction)

6. .The researcher will be lucky if the case report will be
including multiple signs, phenomena, and syndromes.
. Relatives of the patient may help the researcher, indirectly
by providing very old strong data files; such as ECG tracing
for more than 20 years ago.
. The physician should be a strong observer of the new
clinical findings.

7. Abstract

8. Rationale: CHARGE syndrome or Hall-Hittner syndrome is a pleiotropic disorder, in which the name is derived from the
abbreviation epitomizing its six clinical criteria: ocular coloboma, cardiac defects, choanal atresia, growth or
developmental retardation, genital hypoplasia, and ear anomalies or deafness. Wolff-Parkinson-White syndrome is the
most frequent pattern of ventricular pre-excitation. Patent ductus arteriosus is one of the most frequent congenital heart
diseases due to failure of closure of the ductus arteriosus within 72 hours of birth. CHARGE syndrome, Wolff-Parkinson-
White syndrome, and patent ductus arteriosus are so difficult to be present in a single entity.
Patient concerns: A young female girl patient presented to the physician outpatient clinic with acute confusion status
with a past repaired patent ductus arteriosus.
Diagnosis: CHARGE syndrome hallmarked with Wolff-Parkinson-White syndrome and patent ductus arteriosus; 20 years
post-repairing.
Interventions: Plain chest x-ray, electrocardiography, oxygenation, and echocardiography.
Outcomes: A dramatic clinical improvement post-oxygenation had happened.
Lessons: CHARGE syndrome with Wolff-Parkinson-White syndrome and repaired patent ductus arteriosus is an
extreme combination. The existence of infantile electrocardiographic Tee-Pee sign of hypocalcemia and adult low ionized
calcium with CHARGE syndrome is highly suggestive of associated DiGeorge phenotype syndrome. An absence of
tachycardia post- repairing of patent ductus arteriosus from 11 mo until the 20th-year-old is a good prognostic sign. The
presence of an infantile T-wave alternance will strengthen both the risk of serious arrhythmia and the efficacy of patent
ductus arteriosus repairing.

9. Vocabulary or keys for the current case
report

10. .CHARGE syndrome
. Wolff-Parkinson-White syndrome
. Patent ductus arteriosus
. DiGeorge phenotype syndrome
. Tee-Pee sign

11. Discovery history

12. .CHARGE syndrome
.First described in 1979; Pagon et al.(1981)
. Genetic Dx; in 2004; Vissers et al.
. Wolff-Parkinson-White syndrome
.1930; Louis Wolff (American cardiologist), John Parkinson (English cardiologist), and Paul Dudley White (American
cardiologist)
. Patent ductus arteriosus
. 1550; by Servetus and Colombo
. DiGeorge syndrome
.1968; by American physician Angelo DiGeorge
. Tee-Pee sign
. 2009 by Amer M Johri (Clinician scientist)

13. Identification of keys of the case

14. 1. CHARGE syndrome
• CHARGE syndrome (formerly known as CHARGE association) is a rare syndromecaused by a genetic
disorder.
• About two-thirds of cases are due to a CHD7 mutation.
• CHARGE syndrome occurs only in 0.1–1.2 per 10,000 live births.
• As of 2009, it was the leading cause of congenital deaf-blindness in the US.
• CHARGE syndrome is a Mnemonic for:
 C – Coloboma of the eye, central nervous system anomalies
 H – Heart defects
 A – Atresia of the choanae
 R – Retardation of growth and/or development
 G – Genital and/or urinary defects (hypogonadism, undescended testicles, besides hypospadias)
 E – Ear anomalies and/or deafness and abnormally bowl-shaped and concave ears, known as "lop ears".

15. 2. Patent ductus arteriosus
• Patent ductus arteriosus (PDA) is a medical condition in which the ductus arteriosus fails to close after birth.
• Associations and risk factors; Preterm birth, Congenital rubella syndrome, Down syndrome, Loeys–Dietz
syndrome, Wiedemann–Steiner syndrome, CHARGE syndrome, and Fetal Alcohol Spectrum Disorder.
• Common symptoms and signs; dyspnea, tachycardia, continuous "machine-like" (rolling-thunder" or "to-and-
fro") murmur, cardiomegaly, left subclavicular thrill, bounding pulse, widened pulse pressure, increased cardiac
output, increased systolic pressure, differential cyanosis, and poor growth.
• Symptomatic PDA can be treated with both surgical and non-surgical methods. Neonates without adverse
symptoms may simply be monitored as outpatients. Surgically, the DA may be closed by ligation
• Echocardiography and associated Doppler studies are the primary methods of detecting PDA.
• Prostaglandin inhibitors; NSAIDs such as indomethacin or ibuprofen have been used to initiate PDA closure.
• Alprostadil, a PGE-1 analog, can be used to keep a PDA open until the primary defect is corrected surgically.

16. 3. Wolff–Parkinson–White syndrome
(WPWS)
• Wolff-Parkinson-White (WPW) syndrome is a congenital cardiac preexcitation syndrome
that arises from abnormal cardiac electrical conduction through an accessory pathway.
• It can result in symptomatic and life-threatening arrhythmias
• The hallmark electrocardiographic (ECG) finding of WPW pattern or preexcitation
consists of a short PR interval (<120 ms), prolonged QRS complex (>120 ms), and a QRS
morphology consisting of a slurred delta wave.
• Asymptomatic patients with WPW patterns do not require any immediate treatment.
• EP study is reasonable, and ablation is reasonable for accessory pathways found to be either
at high risk or in patients with high-risk occupations.

17. 4. DiGeorge syndrome
(22q11.2 deletion syndrome)
• DiGeorge Syndrome (DGS) is a primary immunodeficiency, often but not always,
characterized by cellular (T-cell) deficiency, characteristic facies, congenital heart
disease, and hypocalcemia.
• Approximately 90% of patients with DGS have a small deletion in chromosome number 22
at position 22q11.2.
• Patients with DGS may have any or all of the following: unusual facial appearance,
heart defects, thymus gland abnormalities, hypoparathyroidism, hypocalcemia, and
developmental abnormalities including cleft palate, poor function of the palate, delayed
acquisition of speech, and difficulty in feeding and swallowing.

18. 5. Tee-Pee Sign
• Tee-Pee sign is an ECG sign that is seen in hypocalcemia with the shape of the QRS-
complexes resembling the traditional shape of native American Indians dwelling (Figure-
1).
• The combination of prolongation of both the ST-segment and descending limb of the T-
wave resulted in pseudo-prolongation of the QT interval (Figure-1).
Figure-1 shows the traditional shape of native American Indians dwelling.

19. Case presentation

20. 1. Complaint and History
• A 20-year-old single, student, young, Egyptian female patient presented to the
POC with acute confusion state
• Her mother gave a history of PDA since 3 mo after developing ARDS , severe
PHT, and repaired on 11 mo.
• The patient had a simultaneous history of tachycardia (of VR; 160 bpm) with
WPW syndrome only before repairing PDA.
• With increasing age, the mother had started to notice the difficulty of learning,
intellectual defects, blurred vision, diminished hearing, intermittent mucus nasal
discharge, intermittent nasal obstruction, growth retardation, amenorrhea, and
hypogonadism.
• Otherwise tachycardia, the mother frequently had consulted the specialists for the
above complaints.

21. 2. Physical examination
• Generally; the patient seemed mentally retarded, infantile facies, small eyes, deaf, glassy blurred vision with iris
defects.
• Vital signs; Pulse rate was regular at VR; 68 bpm, blood pressure (BP) of 110/70 mmHg, respiratory rate of 16 bpm,
the temperature of 36.8 °C, and pulse oximeter of oxygen (O2) saturation of 98%.
• No more relevant clinical data were noted during the clinical examination.
Figure 2-Patient face showing coloboma (lime arrows) microphthalmia (purple arrows) and bilateral choanal atresia (light blue
arrows).

22. 3. Workup
A. Plain CX-Rays
Figure 3: A-Plain Chest X-Ray film was taken on the 5th mo. of life showing enlargement of RV (lime arrows) and RA
(golden arrows). B-Plain Chest X-Ray was taken after 20 years after PDA closure showing no abnormalities.

23. B. ECG
Figure 4; A-ECG tracing was taken on the 3rd mo. of life showing WPW syndrome with delta waves (red arrows), wide QRS (purple rectangle), and short P-R
interval (green rectangle). There is a T-wave alternance in V2,4,5, and V6 (lime and golden arrows). There is also a Tee-Pee sign of hypocalcemia (green arrows). P-
and delta waves are inverted in V1 ((blue arrows). B-ECG tracing was taken after 20 years after PDA closure showing WPW syndrome with delta waves (red
arrows), wide QRS (purple rectangle), and short P-R interval (green rectangle). There is no T-wave alternance (lime arrows). P and delta waves are upright in V1 (blue
arrows).

24. C. Echocardiography
Figure 5; A- Echo Doppler image was taken on the 3rd mo of life showing diastolic turbulence. B - Echo
Doppler image was taken after 20 years after PDA closure showing no abnormality.

25. D. Other workup
• The current complete blood count (CBC); Hb was 11.9 g/dl, RBCs; 5.15*103/mm3, WBCs;
9.7*103/mm3 (Neutrophils; 63.3 %, Lymphocytes: 28.4%, Monocytes; 7.6%, Eosinophils; 0.5%
and Basophils 0.2%), MCV was low (77.3 fl), MCH was low (23.1 pg), MCHC was low (29.9
g/dl), Platelets; 406*103/mm3.
• D-dimer was normal (100 ng/ml).
• CRP was normal (less than 1 g/dl).
• S. Ferritin was low (8.13 ng/ml).
• SGPT was normal; 18 U/L, SGOT was normal; 33 U/L.
• Both Serum creatinine showed ( 0.7 mg/dl) and blood urea (25 mg/dl) was normal.
• RBS was normal (84 mg/dl).
• Ionized calcium was mildly low; 0.83 mmol/L.
• The troponin test had become negative.

26. The most probable diagnosis
• CHARGE syndrome hallmarked with Wolff-
Parkinson-White syndromes and patent ductus
arteriosus; 20 years post-repairing

27. Treatment
• The patient was only treated with O2 inhalation by O2
cylinder (100%, by nasal cannula, 5L/min). A dramatic
clinical improvement post-oxygenation had happened.
• Oral calcium, vitamin-D preparation, and iron
supplements for 30 days were prescribed with further
recommended cardiac and endocrinologist follow-up.

28. Discussion
• Overview: A young female girl patient presented to POC with acute confusion status with a past repaired PDA.
• The objective primary for my case study was the presence of CHARGE syndrome with ECG WPWS and
repaired PDA.
• The secondary objective for my case study was the question of; How did you manage the case?
• The presence of coloboma (microphthalmia with blurred vision), heart defects (PDA), atresia of the choanae
(intermittent nasal obstruction and mucus nasal discharge), retardation (of growth, intellectual, and learning),
genital defects (hypogonadism, amenorrhea), and ear anomalies (diminished hearing) support diagnosis.
• The presence of infantile ECG T-wave alternance maybe reflect the efficacy of PDA repairing.
• The existence of infantile ECG Tee-Pee sign of hypocalcemia and adult low ionized calcium in charge is an
interesting
• Suspected iron deficiency anemia may interpret the acute confusion status which was dramatically responded to
O2 inhalation.
• The only limitations of the current study were the unavailability of genetic counseling and diagnostic test.

29. Acknowledgment
•I wish to thank Ahmed Alghobary, B.sc. for his
technical support.

30. Conclusion and Recommendations
• CHARGE syndrome with Wolff-Parkinson-White syndrome and repaired patent
ductus arteriosus is an extreme combination.
• The existence of infantile ECG Tee-Pee sign of hypocalcemia and adult low
ionized calcium with CHARGE syndrome is highly suggestive of associated
DiGeorge phenotype syndrome.
• An absence of tachycardia post- repairing of PDA from 11 mo until the 20th-year-
old is a good prognostic sign.
• The presence of an infantile T-wave alternance will strengthen both the risk of
serious arrhythmia and the efficacy of the repairing of patent ductus arteriosus.

31. References
1. Pagon RA, Graham JM, Zonana J, Yong SL . Coloboma, congenital heart disease, and choanal atresia with multiple
anomalies: CHARGE association. J. Pediatr. 1981;99 (2): 223–7. DOI:10.1016/S0022-3476(81)80454-4. PMID 6166737.
2. The 2008 National Child Count of Children and Youth who are Deaf-Blind. The National Consortium on Deaf-Blindness.
2009. p. 30. Archived from the original on 2012-03-15.
3. Medline Plus. Patent ductus arteriosus Update. Date: December 21, 2009.
4. Zahaka, KG and Patel, CR. Congenital defects. Fanaroff, AA and Martin, RJ (eds.). Neonatal-perinatal medicine: Diseases of
the fetus and infant. 7th ed. 2002:1120–1139. St. Louis: Mosby.
5. Mosalli R, Alfaleh K, Paes B. Role of prophylactic surgical ligation of patent ductus arteriosus in extremely low birth weight
infants: Systematic review and implications for clinical practice. Ann Pediatr Cardiol. July 2009;2 (2): 120–6. DOI:10.4103/0974-
2069.58313. PMC 2922659. PMID 20808624.
6. Chhabra L, Goyal A, Benham MD. Wolff Parkinson White Syndrome. [Updated 2021 Aug 11]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554437/
7. Johri AM, Baranchuk A, Simpson CS, Abdollah H, Redfearn DP. ECG manifestations of multiple electrolyte imbalance:
peaked T wave to P wave ("tee-pee sign"). Annals of Noninvasive Electrocardiology 2009 Apr;14(2):211-214. DOI:
10.1111/j.1542-474x.2009.00283.x. PMID: 19419407; PMCID: PMC6932546.
8. Elsayed YMH. Charge Syndrome Hallmarked with Wolff-Parkinson-White Syndrome and Patent Ductus Arteriosus; 20 Years
Post-Repairing; An Extreme Combination. International Journal of Healthcare and Medical Sciences. 2021;7(3):26-30. DOI:
https://doi.org/10.32861/ijhms.73.26.30.

32. Thank you