“SANDIFER SYNDROME IN A THREE WEEK OLD MALE: A CASE REPORT”

Michelle Gale R. Mejia, M.D., Jean Cathlene D. Banzon, M.D., Tyrone Yap, M.D.

ABSTRACT

Rationale:
Sandifer Syndrome is a rare pathologic form of gastroesophageal reflux disease
with irritability and abnormal neurobehavioral movements such as eye version, torticollis,
extensor spasm and dystonic posture. The occurrence of these symptoms together with
cyanotic paroxysms, is to be discussed in this study.

Objective:
This case report aims to discuss a pathology which had an usual presentation at
a very young age, with less than 10 cases reported in Asia. It will identify and exclude
differentials of the presenting symptoms by system in a multidisciplinary approach.

Methodology:
This is a case report on a 3 week old male, who had multiple episodes of circumoral
cyanosis since 1st week of life, noted after feeding. This was accompanied by bradycardia
and desaturation episodes, upward rolling of eyeballs, stiffening of extremities and
drooling, which would spontaneously resolve.

Results:
Work up was done showing neither evidence of metabolic, cardiovascular or
neurologic pathology causing cyanotic episodes. CBC showed normocytic normochromic
anemia, normal WBC, with thrombocytosis, normal CRP, normal ABG, but with a
confluence in left lower lung probably consolidation vs atelectasis vs aspiration. Hence,
empiric antibiotic therapy was started and completed for 10 days since with negative
blood culture. Newborn screening test and electrolytes were normal. 2d echo showed
congenital heart disease, acyanotic, atrial septal defect, secundum. Cranial ultrasound
and EEG were normal. Barium swallow showed gastroesophageal reflux; thus,
Esomperazole and Domperidone were started. Small frequent and thickening of feeds
also helped lessen the episodes. After 1 month, from 10-15 episodes, it has lessened to
3-5 episodes per day.

Conclusion
This case is an atypical presentation of pediatric GERD presented at a very young
age, with paroxysms of cyanosis, which responded to pharmacological and supportive
therapy. Although the course of the disease may be variable, immediate work up, imaging
and intervention is of outmost importance on the onset of cyanotic attacks.

Keywords: Sandifer Syndrome, Infantile Reflux, Case Report

1
INTRODUCTION

In infants, gastroesophageal reflux (GER) is a benign process, which presents with

brief regurgitation epsiodes post feeding, still with good oral intake, activity in between
and with unremarkable weight loss. This would occur at least once per day in 50% of 0 to
3 month old infants. However, if accompanied by complications such as poor weight gain,
esophagitis and respiratory symptoms, this condition is termed as gastroesophageal
reflux disease (GERD).1

Sandifer Syndrome is a rare pathologic form of gastroesophageal reflux disease.

Irritability and abnormal neurobehavioral movements such as eye version, torticollis,
extensor spasm, dystonic posture, which can also present with cyanotic paroxysms, occur
as seen in this case.2 So far, there have been only less than 10 cases documented in
Asia, wherein other conditions that may present with the aforementioned symptoms were
eliminated per system in a multidisciplinary approach,3 as what was done for our patient.
This syndrome is usually not immediately recognized and delay in the diagnosis occur
due to its atypical presentation.

The purpose of this case report is to discuss a pathology, which occurred at a very
young age and an usual presentation of GERD. It aims to identify and exclude differentials
of presenting the of symptoms by system, and its multidisciplinary approach.

PATIENT INFORMATION

This is a case of a 3-week old male, who was admitted at our institution for the first
time on November 5, 2019, with a chief complaint of circumoral cyanosis.

The patient was born full term to a then 39 year old G6P6 (6006) via normal
spontaneous delivery in a government tertiary hospital, assisted by an obstetrician with a
birth weight of 2.68 kg and unrecalled birth length and apgar score. Mother noted vigorous
cry and good activity upon birth. There were no fetomaternal complications. Routine
newborn care was done, then patient was discharged after 4 hospital days. The patient’s
mother had monthly prenatal checkups since 8 weeks age of gestation. She denies any
infections. His newborn screening, hearing, and critical congenital heart disease
screening tests were normal. He was mixed fed with breastmilk (6-8 times a day; 15-20
minute duration) and milk formula (1:1 dilution), 2 ounces per bottle, and consumed 2-3
bottles per day.

Since birth, the patient had good suck and activity but was noted to have
occasional episodes of circumoral cyanosis lasting for 1 minute occurring after feeding
and while asleep for approximately 3-5 episodes per day which would spontaneously
resolve. There were no other associated symptoms such as upward rolling of eyeballs,
stiffening of extremities, vomiting, fever, cough, or difficulty of breathing. No medications
were given. No consult was done.

2
 Two days prior to admission, patient had non-productive cough, noted post-feeding
with associated circumoral cyanosis as previously described with no other symptoms.
Still, no consult was done and no medications were given.

One day prior to admission, there were still persistent episodes of circumoral
cyanosis, accompanied by non-productive cough, now with associated stiffening of upper
and lower extremities which spontaneously resolved after 1 minute. There was no upward
rolling of eyeballs, and no other associated symptoms such as vomiting, difficulty of
breathing, and arching of the back. The patient was brought to a local health clinic. He
was discharged stable with an undisclosed diagnosis, with no medications, and was
advised to monitor for recurrence.

Two hours prior to consult, there was recurrence of the circumoral cyanosis post-
feeding associated with drooling and stiffening of extremities for 1 minute followed by a
period of unresponsiveness despite stimulation for an unrecalled length of time. The
patient was brought to another institution and was initially given oxygen supplementation.
Upon palpation of the abdomen, the patient had an episode of vomiting of milk which was
non-bilious, non-projectile, approximately 60 ml in amount. He subsequently regained
consciousness thereafter. CBCP was done which showed normal results. During the
consult, there was no recurrence of symptoms, with noted good suck and activity. The
patient was advised admission for further observation and workup, however, was
transferred to our institution due to parent’s preference.

The review of systems showed no decrease in activity, no weight loss, no

tachypnea, no difficulty of breathing. Past medical history was unremarkable. His
immunizations were complete for age. He has a family history of febrile seizure on the
paternal side, but with no family histories of heart and lung diseases. Environmental
history revealed 2 sick siblings with symptoms of cough and colds. He was noted to be
developmentally at par.

CLINICAL FINDINGS

On physical examination, the patient was active with stable vital signs. His
anthropometrics were normal for age. He had no pallor and had good skin turgor. He has
sunken open anterior and posterior fontanels. His eyes, ears nose, throat, and neck
examination were normal. Cardiovascular examination showed regular rhythm, and no
murmurs. Respiratory examination showed no adventitious breath sounds. Abdominal
examination showed soft non distended abdomen with normoactive bowel sounds.
Genitalia, anorectal, musculoskeletal examination were unremarkable. For the neurologic
exam, patient was easily arousable, with flat fontanelles, good tone and spontaneous
movements, no facial asymmetry, with no motor deficits, with intact primitive reflexes and
with no pathologic reflexes.

3
TIMELINE
Date Relevant Past Medical History and Interventions
The patient was born full term to a then 39 year old G6P6 (6006) via normal
spontaneous delivery in a government tertiary hospital, assisted by an obstetrician with
Oct 14, 2019 a birth weight of 2.68 kg and unrecalled birth length and apgar score. Mother noted
vigorous cry and good activity upon birth. His newborn screening, hearing, and critical
congenital heart disease screening tests were normal.
Oct 14, 2019 The patient had good suck and activity but was noted to have occasional episodes of
to circumoral cyanosis lasting for 1 minute occurring after feeding and while asleep for
Nov 2, 2019 approximately 3-5 episodes per day which would spontaneously resolve.
Nov 3, 2019 The patient had non-productive cough, noted post-feeding with associated circumoral
cyanosis.
There were still persistent episodes of circumoral cyanosis, accompanied by non-
productive cough, now with associated stiffening of upper and lower extremities which
Nov 4, 2019 spontaneously resolved after 1 minute. The patient was brought to a local health clinic.
He was discharged stable with an undisclosed diagnosis, with no medications, and
was advised to monitor for recurrence.
Two hours prior to consult, there was recurrence of the circumoral cyanosis post-
feeding associated with drooling and stiffening of extremities for 1 minute followed by
a period of unresponsiveness despite stimulation for an unrecalled length of time. The
Nov 5, 2019, patient was brought to another institution and was initially given oxygen
PM supplementation. Upon palpation of the abdomen, the patient had an episode of
vomiting of milk which was non-bilious, non-projectile, approximately 60 ml in amount.
He subsequently regained consciousness thereafter. CBCP was done which showed
normal results. During the consult, there was no recurrence of symptoms, with noted
good suck and activity. The patient was advised admission for further observation and
workup, however, was transferred to our institution due to parent’s preference.
The patient was brought to the emergency room and had a recurrence of circumoral
cyanosis with associated head and neck extension, arching of the back, stiffening of
extremities, drooling, bradycardia at 50 bpm, and desaturation of 89% at room air.
Nov 5, 2019, Cardiopulmonary resuscitation was done. Bag-mask-valve ventilation and chest
PM compressions were performed for 2 minutes. Heart rate increased to 100 bpm
thereafter and the patient was then noted to have good cry and activity with resolution
of the cyanosis. Blood pressure was 70/50mmHg, and his respiratory rate was 45cpm.
CBG was noted to be normal at 115 mg/dl. IV bolus of PNSS at 10 cc/kg was given.
The patient was put on NPO, hooked to oxygen at 2 lpm via nasal cannula, started on
IV hydration, and put on seizure precaution.
Dates Summaries from Initial and Diagnostic Testing Interventions
Follow-up visits
Patient was admitted and CBCP: normocytic, Patient was hydrated,
managed by service of normochromic anemia, and started on
Neonatalogy. Impression was normal WBC, segmenter Ampicillin (200
Clinical sepsis to consider predominance, mg/kg.day) and
gastroesophageal reflux, rule thrombocytosis Gentamicin
Nov 5, 2019 out seizure disorder. CRP: normal (4mg/kg/day).
Blood CS: negative Orogastric tube was
st
1 hospital ABG: normal inserted and feeding
day Electrolytes: normal initiated at only 5mL
Cranial ultrasound: every 3 hours.
normal
Chest x-ray: confluence
in the left lower lung
probably consolidation vs
atelectasis vs aspiration

4
 The patient had 12 to 15 Barium swallow Patient was started on
episodes of circumoral test/Esophagogram: Esomeprazole (0.8
cyanosis per day which lasted Gastroesophageal reflux mg/kg/day) once a day
for 30 seconds associated by unitl the thoracic inlet and Domperidone
stiffening of extremities, (0.25mg/kg/dose)
arching of the back, drooling, every 8 hours.
Nov 6-7, bradycardia of 60 bpm, and
2019 desaturation of 60% at room
nd rd air which occurred post-
2 -3
feeding, which resolved
hospital day
spontaneously. Assessment at
this time was still clinical
sepsis, to consider
gastroesophageal reflux
disease, to rule out
tracheoesophageal fistula.

Due to persistence of cyanotic 2D Echocardiogram No medications were

episodes, the patient was with Color Doppler: given. Plan is to repeat
Nov 8, 2019 referred to cardiology service Congenital Heart 2D echocardiogram
to rule out cyanotic congenital Disease, Acyanotic, Atrial with doppler at 6
th
4 hospital heart disease. Septal Defect, months of age.
day Secundum, Left
Pulmonary Artery
Stenosis, Mild, Mild
Tricuspid Regurgitation

The patient had decreased Blood CS: negative for 7 Plan wass to complete
episodes of circumoral days Ampicillin and
cyanosis to 8 times lasting for Repeat Chest X-ray: Gentamicin for 10
30-45 seconds with significant clearing of the days. Esomeprazole
associated arching of the confluent opacities in the was increased to 1.5
Nov 11, 2019 back, stiffening of extremities, left lower lung, as well as mg/kg/day.
bradycardia lowest at 70 bpm the patchy haziness in Non-pharmacologic
th
7 hospital and desaturation lowest of the right lower lung, with measures were done
day 70% post feeding. mild prominence of the such as thickening of
interstitial markings feeds with rice cereals
The patient was referred to bilaterally which may and placing the patient
gastroenterology service due represent airway on prone position at a
to persistence of circumoral inflammation or infection. 45-degree angle for 30
cyanosis despite 3 days of minutes post-feed.
esomeprazole and
domperidone.
He had 10 more episodes of Sleep and awake EEG: No new intervention
circumoral cyanosis lasting for normal
30-45 seconds still with
associated bradycardia lowest
Nov 12, 2019 at 70 bpm and desaturation
lowest of 60% post feeding.
th
8 hospital Since there was persistence
day of the cyanotic episodes
despite 5 days of
esomeprazole and
domperidone, the patient was
referred to Neurology service.

5
 The patient’s cyanotic
episodes have decreased to
5-8 per day, with occasional
bradycardia and desaturation.
Hence, he was cleared for
Nov 16, 2019 discharge on all services.
Final diagnosis is
th
12 hospital Gastroesophageal reflux
day disease (Sandifer syndrome);
Neontal Pneumonia Atrial
septal defect secundum, mild
acyanotic left pulmonary
stenosis, mild tricuspid
regurgitation.
One week after discharge, the Esomeprazole was
patient followed up at the continued for 2 more
Nov 23, 2019 OPD, noted that cyanotic weeks.
episodes have decreased to 3
Follow up episodes per day. He is
tolerating breastfeeding.
Four months after discharge,
he had no recurrence of the
cyanotic episodes. He is
March 2020 feeding well, consuming 3-4
bottles per day, 3oz per bottle
Follow up and breastfeeding as tolerated
with occasional coughing and
minimal regurgitation of milk
post-feeding. He is also noted
to be developmentally at par.

6
DIAGNOSTICS ASSESSMENT

A. Laboratory tests

Table 1. Complete Blood Count

1st Hospital Day
Hemoglobin (g/dL) 9.1 (L)
Hematocrit (%) 27 (L)
RBC (10^9/L) 2.9
MCV (fL) 91
MCH (pg) 31
RDW (mL) 0.146
WBC (10^9/L) 8.39
Segmenters 49 9 (H)
Lymphocytes 36 (L)
Monocytes 12
Eosinophils 2
Basophils 1
Platelet (10^12/L) 439 (H)

Table 2. Blood Chemistry

1st Hospital Day
Capillary Blood Glucose (mg/dL) 115
C-Reactive protein <6
Sodium (mmol/L) 136
Potassium (mmol/L) 4.60
Ionized Calcium (mmol/L) 1.24
Chloride (mmol/L) 105

Table 3. Arterial Blood Gas

1st Hospital Day

pH 7.463
pCO2 25.7
pO2 176
HCO3 20.7
ABE -4.4
Table 4. Microbiology

Blood culture and No growth after 7 days of

sensitivity incubation

7
B. Chest X-ray

(A) (B)

Figure 1. (A) Confluence is seen in the left lower lung. Mild patchy haziness is seen in
the right lower lung. No pleural effusion or adenopathy. Heart is not enlarged.
Hemidiaphragms and bony thorax are intact. Note of an enteric tube with its tip in the area
of the stomach. Impression: consider consolidation, atelectasis, or aspiration (B) Follow-
up study since november 5, 2019 shows significant clearing of the confluent opacities in
the left lower lung, as well the patchy haziness in the right lower lung. Findings may relate
to regression of the consolidation, atelectasis, or aspiration. There is mild prominence of
the interstitial markings bilaterally, which may represent airway inflammation or infection,
Heart is not enlarged. The rest of the study remains unchanged.

8
C. Barium swallow test

Figure 2. Esophagogram Mucosal pattern is normal with no area of irregularity No

narrowing or dilatation. Peristalsis is within normal limits. No intrinsic abnormality is seen
in the esophagus. No tracheoesophageal fistula was demonstrated. Reflux of contrast is
noted up to the level of thoracic inlet. No aspiration observed during the examination.
Impression: Gastroesophageal reflux

D. Two dimensional echocardiography with Doppler study

Abdominal and atrial situs solitus; atrioventricular and ventriculoarterial concordannce;

atrial septal defect, secundum, measuring 0.3 to 0.4 cm with minimal left to right shunting,
intact interventricular septum, no chamber enlargement, normal atrioventricular and
semilunar valves, no outflow tract obstruction; left poulmonary atrial stenosis with peak
gradient of 18 mmHg, good left ventricular systolic and diastolic functions (EF of 71%),;
mild tricuspid regurgitation; TR Jet 16.5 mmHg; left-sided aortic arch; all pulmonary veins
drain to left atrium; no patent ductus arteriosus/coarctaion/pericardia
leffusion/vegetation/thrombus; moderately elevated pulmonary artry pressure estimated
at 54 mmHg based on pulmonary acceleration time of 90 msec. Assessment: Congenital
Heart Disease, Acyanotic, Atrial Septal Defect, Secundum, Left Pulmonary Artery
Stenosis, Mild, Mild Tricuspid Regurgitation.

E. Cranial ultrasound

Ventricles are normal in size; no hemorrhage, hydrocephalus, or midline shift. No focal

asymmetry or cystic changes seen in the parenchyma; echogenicity is within normal
limits. No abnormal collection in the extra-axial spaces. Unremarkable midline sutures.
Unremarkable posterior fossa. Superior sagittal sinus is patent. Impression: Examination
is within normal limits

9
F. Sleep and awake EEG

The background activity while awake consists of a mixed medium voltage predominantly
theta rhythym of 5-7 Hz with occasional alpha waves of 8-9 Hz bilaterally symmetric,
There are occasional 3-4 Hz activity admixed with the background. Numerous movement
related artifacts are seen especially during the awake state. Midway through the study,
the pateint becomes drowsy and progresses into sleep. Photic stimulation did not elicit
an occipital driving response. No epileptiform discharges were seen. Impression: This is
a normal EEG for age predominantly in both awake and sleep states.

THERAPEUTIC INTERVENTION

Patient was hydrated and orogastric tube to initiate feeding at only 5mL every 3
hours initially. Pharmacological management included administration of Ampicillin (200
mg/kg/day) every 8 hours and Gentamicin (4mg/kg/day) once a day. He was also started
on Esomeprazole (0.8 mg/kg/day) once a day and Domperidone (0.25mg/kg/dose) every
8 hours. Due to persistence of cyanotic episodes and incomplete clearing of hazy
opacities and new interstitial markings associated with infection on x-ray, Ampicillin and
Gentamicin were completed for 10 days. Also, esomeprazole was increased to 1.5
mg/kg/day due to persistence of cyanotic episodes. Non-pharmacologic measures were
done such as thickening of feeds with rice cereals and placing the patient on prone
position at a 45-degree angle for 30 minutes post-feed. Surgical management was not
considered for this patient, since there was gradual resolution of symptoms with
pharmacological and non-pharmacological therapy

FOLLOW UP AND OUTCOME

One week after discharge, the patient followed up at the OPD, noted that cyanotic
episodes have decreased to 3 episodes per day. He was tolerating breastfeeding.
Esomeprazole was continued for 2 more weeks and was followed up via phone consult
due to missed consult at OPD.

Four months after discharge, he had no recurrence of the cyanotic episodes. He

was feeding well, consuming 3-4 bottles per day, 3oz per bottle and breastfeeding as
tolerated with occasional coughing and minimal regurgitation of milk post-feeding. Also
noted with weight gain, no recurrence of previous symptoms and developmentally at par.
No laboratory tests and imaging studies were needed at this point and patient was
monitored clinically, and advised parents that with age and growth of anatomical
structures, his condition will completely resolve.

10
DISCUSSION

Gastroesophageal reflux is the most common esophageal disorder of children in

most age groups.4 It is a physiologic process that may be present among healthy infants,
which will not cause life threatening complications. In particular, infantile reflux may
manifest in the first few months of life, peaks at 4 months, decreasing by 6 to 7 months
and spontaneously resolves by 24 months. However, a problem arises when red flags to
this condition are present.5 In this case, the age of presentation, neurologic-like symptoms
and cyanosis were alarming.

In a neonate presenting with cyanosis, it must first be identified as either peripheral

or central cyanosis. Peripheral cyanosis or acrocyanosis refers to an increase in tissue
oxygen utilization in the capillary bed or hypoxemia, which manifests as violaceous
extremities. However, this is without hypoxia or with normal systemic arterial oxygen
saturation.6 On the other hand, central cyanosis is associated with a low arterial partial
pressure of oxygen and low hemoglobin oxygen saturation This involves the skin, mucous
membranes, lips, tongue, and nail beds. 7 Our patient presented with circumoral cyanosis
accompanied by desaturation. Hence, this was classified as central in cause. Central
cyanosis was differentiated in terms of etiology to reach a diagnosis. This may be
classified as either respiratory, infectious, metabolic, neurologic, cardiac, and
gastrointestinal causes.

Respiratory diseases causing cyanosis in neonates include congenital defects,

airway obstruction, and primary pulmonary disease.7 Congenital defects present with
cyanosis, desaturation with signs respiratory distress such as tachypnea, retractions,
wheezing, and unequal breath sounds that are prominent at birth,7 but was not seen in
our patient. Airway obstruction present with a history of purulent nasal discharge or nasal
obstruction, enlarged tongue, unequal breath sounds and stridor.7 However, these
findings were not present in our patient. On the other hand, primary pulmonary diseases
is the most common cause of neonatal cyanosis. Specifically, pneumonia is an acute
inflammatory response to the alveoli causing ventilation-perfusion mismatch leading to
cyanosis.7 In this case, with a history of cough and colds, also similar symptoms with
siblings, and chest x-ray finding of a confluence in the left lower lung probably
consolidation vs atelectasis vs aspiration, Neonatal pneumonia was considered.

Infectious causes such as clinical sepsis is the second most common cause of
neonatal cyanosis. It causes increased oxygen utilization, which results in cyanosis.7
Non-specific symptoms of sepsis include temperature instability, lethargy, tachypnea,
hypoxia, tachycardia/bradycardia, poor perfusion manifesting as cyanosis, and
hypotension.8 Since the patient presented with cyanosis, bradycardia, and hypoxia, also
with exposure to cough and colds, septic workup was done. Results showed normocytic,
normochromic anemia, normal WBC and thrombocytosis on CBCP, as well as
consolidation in left lower lung on chest xray. Hence, empiric antibiotic therapy namely
Ampicillin and Gentamycin, were started and completed for 10 days since with negative
blood culture.

11
 Despite starting the antibiotics cyanotic episodes persisted, hence other etiologies
of cyanosis were examined. One of which are the metabolic abnormalities that could
present with cyanosis including drug withdrawal and inborn errors of metabolism. These
occur with hypoglycemia, electrolyte imbalance and metabolic acidosis. Hypotonia,
lethargy, and seizures may also be present.9 Our patient had normal newborn screening
test, capillary blood glucose, electrolytes, arterial blood gas and was not hypotonic or
lethargic. Metabolic cause for cyanosis was ruled out, however the seizure-like
manifestation warranted further investigation.

Neurologic dysfunctions, such as hypoxic ischemic encephalopathy, intracranial

hemorrhage, or seizure disorder may cause hypoventilation and apnea resulting in
hypoxemia and cyanosis. 10 Epileptic neonatal seizures are focal and present with
repetitive rhythmic contractions of specific muscle groups which is focal clonic or
sustained asymmetrical posturing of the trunk or the single limbs which is focal tonic.
There may be changes in vital signs such as oxygen desaturation and tachycardia.11 Our
patient presented with posturing of the trunk and desaturation but with bradycardia
instead of tachycardia. Cranial ultrasound as well as sleep and awake encephalography
showed normal results. Hence, neurologic cause of cyanosis were least likely considered.

A cardiac pathology that may cause cyanosis was important to be assessed due
to an increased risk of mortality if the condition is not detected. Congenital heart diseases
that present in the first weeks of life are ductal-dependent cardiac lesions. This include
tricuspid atresia, tetralogy of fallot, transposition of the great arteries, truncus arteriosus,
and total anomalous pulmonary venous return.12Our patient did not present with a single
S2 or any murmur. Chest x-ray showed a cardiothoracic ratio is 0.5, which was normal.
2D echocardiogram revealed mild pulmonary stenosis, tricuspid regurgitation and atrial
septal defect, secundum. These pathologies were all acyanotic in nature, hence did not
explain the patient’s condition.

Gastrointestinal causes of cyanosis include tracheoesophageal fistula and

gastroesophageal reflux. Tracheoesophageal fistula, particularly the H-type, present with
coughing, choking since birth, and cyanosis associated with feeding as the milk is
aspirated through the fistula.13 However this was least likely for our patient. On the other
hand, gastroesophageal reflux cause cyanosis due to the laryngeal chemoreflex.
Receptors in the interarytenoid space mediate aspiration preventive reflex responses
such as swallowing, cessation of breathing, airway constriction or closure, and coughing.
14
This hyperactive laryngeal chemoreflex cause episodic apnea leading to desaturation,
cyanosis, and bradycardia, which were all manifested by the patient. Barium swallow
study revealed reflux of contrast up to the level of thoracic inlet, which confirmed the
diagnosis of gastroesophageal reflux disease.

Our patient presented at a very young age with circumoral cyanosis post feeding,
bradycardia and desaturation, which are red flags of gastroesophageal reflux.
Accompanying signs such as head and neck extension, arching of the back, and stiffening
of extremities only mimic seizures, and are actually defense mechanisms of the disease.
All these combined are manifestations of a condition called Sandifer syndrome

12
 Sandifer syndrome is an uncommon condition characterized by periodic head
movements with neck extension and rotation of the head to one side. This usually occurs
shortly after feeding.15 Its true pathophysiologic mechanism remains unclear. However,
the posturing was attributed to an anatomic defense mechanism against repetitive acid
reflux. Tilting of the head to the side has been suggested to be an unconscious effort to
reduce gastric contractions and to provide relief from abdominal discomfort.15 In fact,
Puntis and his colleagues did an esophageal manometric study, which showed that the
head tilting and dystonic posturing produced an increase in the velocity and amplitude of
the peristaltic waves in the esophagus. This promoted the clearance of acid from the
lower esophagus and thereby relieve the symptoms.16

This syndrome is often overlooked may be due to its atypical presentation, which
could be mistaken for diseases of other organ systems. Hence, it is very important to rule
out life threating conditions that may compromise the patient as what was done in this
case. To further confirm gastroesophageal reflux, diagnostics such as esophageal 24 hr
pH monitoring, manometry, and endoscopy with biopsy can be done, but was not
performed in our patient.17 Once confirmed, both non pharmacological and
pharmacological therapy must be initiated to avoid complications such as aspiration
pneumonia and malnutrition.

CONCLUSION

This case is an atypical presentation of pediatric GERD. It presented at a very

young age, with paroxysms of cyanosis and seizure-like symptoms, which is referred to
as Sandifer syndrome. Although the course of the disease may be variable, immediate
work up, imaging and intervention is of outmost importance on the onset of cyanotic
attacks.

REFERENCES:
1. Campanozzi A, Boccia G, Pensabene L, Panetta F, Marseglia A, Strisciuglio P,
et al. Prevalence and natural history of gastroesophageal reflux: pediatric
prospective survey. Pediatrics. 2009;123(3):779

2. Kabakus ̧N, Kurt A. Sandifer Syndrome: A continuing problem of misdiagnosis.

Pediatrics International. 2006; 48, 622–625

3. Nalbantoglu B, Metin DM, Nalbantoglu A. Sandifer’s Syndrome: a Misdiagnosed

and Mysterious Disorder. Iran J Pediatr. 2013; 23(6): 715-716

4. Khan S, Orenstein SR. Gastroesophageal Reflux Disease. Nelson Textbook of

Pediatrics. 20th ed. Philadelphia: Elsevier, Inc; 2016: 1787-1791

13
5. Rosen R, Vandenplas Y, Singendonk M, Cabana M, Di Lorenzo C, Gottrand F, et
al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint
Recommendations of NASPGHAN and ESPGHAN. J Pediatr Gastroenterol Nutr.
2018;

6. Jyotsna, M et al. Cyanosis-Part 1. Indian Journal of Cardiovascular Diseases

2016;(1):1-5

7. Gomella, T. Neonatology. 7th ed. USA: McGrawHill; 2013: 361-368

8. Nizet V, Klein JO. Bacterial sepsis and meningitis. In: Infectious diseases of the
Fetus and Newborn Infant. 8th ed. Elsevier Saunders:Philadelphia; 2016: 217

9. Shakya, A. Inborn errors of metabolism. Advances in Biochemistry & Applications

in Medicine. 1st ed. India; 2017: 1-29

10. Sasidharan P. An approach to diagnosis and management of cyanosis and

tachypnea in term infants.Pediatr Clin North Am. 2004;51(4):999

11. Elia M, Engel J Jr, Guerrini R, Mizrahi EM, MoshéSL, Plouin P. Proposal of an
algorithm for diagnosis and treatment of neonatal seizures in developing countries.
Epilepsia. 2007;48(6):1158

12. Scholz, T, Reinking B. Congenital heart disease. Avery’s Diseases of the newborn.
10th ed. Saunders Elsevier Inc: Philidelphia; 2012: 762-805

13. Song C, Upperman JS, Niklas V. Surgical abnormalities of the gastrointestinal

tract. Avery’s Diseases of the newborn. 10th ed. Saunders Elsevier Inc:
Philidelphia; 2012: 979-984

14. Thach, B. Reflux associated Apnea in Infants: Evidence for a laryngeal

chemoreflex. The American Journal of Medicine. 1997;3(5): 120-124

15. Lehwald, et al. Sandifer Syndrome-A Multidisciplinary Diagnostic and Therapeutic

Challenge. Eur J Pediatric Surg 2007; 17: 203-206

16. Puntis JW et al.. Effect of dystonic movements on esophageal peristalsis in

Sandifer’s syndrome. Arch Dis Child 1989; 64: 1311-1313

17. Narchi H. A rare under-recognized cause of Pseudo-seizures. International

Pediatrics 2004; 19: 39-41

14
INFORMED CONSENT

Date: ________________
Kung kanino ito maari patungkol:

Kami po ay si Michelle Gale Rocafort Mejia at Jean Cathlene D. Banzon, mga residente na
espesiyalista para sa mga bata, sa Cardinal Santos Medical Center. Nais ko po kayong hingian ng
pahintulot upang maibahagi ang nagging kondisyon ng inyong anak, sa isang report na pinamagatang
“SANDIFER SYNDROME IN A THREE WEEK OLD MALE: A CASE REPORT”.

Ang pag-aaral na ito ay para sa mga doktor upang mabigay gabay ang pangangailangan sa
paganalysa, paggamot at pagaaral ng mga kagayang kaso sa isang neonate na nangingitim pagkatapos
kumain at may mga simtomas na parang seizure.

Kapag pahintulot ay ipinagkaloob, ibabahagi ang mga pangyayari, mga pagsusuri at paggamot na
ginawa sa inyong anak na nagging pasyente sa aming ospital. Maaari niyong ihinto ang partisipasyon ng
bata sa pagsusuring ito kahit anumang oras nang walang multa. Ang tagapanaliksik ay maaring magtanggal
sa kalahok sa pagsusuri kung inaakala niyang makabubuti ito sa kanya. Ang doktor ng pananaliksik na ito
ay walang kaugnayan sa mga kompanya ng gamot na maaaring magbenepisyo sa pagsusuring ito at wala
rin anumang uri ng kabayaran silang matatanggap. Gayundin, walang anumang uri ng kabayaran na
matatanggap ang mga sasali sa pagsusuring ito.

Kung mayroon mga katanungan ukol sa pag-aaral na ito, maari niyong tanungin ng personal ang
tagapanaliksik na nagsasagawa ng pagsusuri na si Dr. Michelle Gale R. Mejia o maari siyang tawagan sa
telepono bilang 7270001 loc 3116 mula 8:00am hanggang 4:00pm.

BATID NA PAHINTULOT

Nabasa ko ang impormasyon na inilahad at detalyadong ipinaliwanag ni Dr. Michelle Gale R. Mejia at
naunawaan ko lahat na maaaring mangyari sa kabuuan ng pananaliksik na ito. Nagtanong ako tungkol sa
mga prosesong gagawin at natugunan ang aking mga katanungan. Napaunawa sa akin na ang paglahok
ay boluntaryo at maaari kong bawiin ang aking pahintulot anumang oras sa anumang dahilan at ang
pagbawi sa aking pahintulot ay walang multa at hindi hahantong sa hindi matuwid na pagtrato sa akin o sa
bata.

Ako ay sumasang ayon na ilahok ang bata sa pagsusuring ito at pumapayag na maisakatuparan ang
anumang nakasaad sa papel na ito. Pagkatapos ko ito lagdaan, ako ay tatanggap ng kopya nito.

___________________________________ __________________ ____________

Pangalan at Lagda ng Nagbibigay Pahintulot Relasyon sa bata Petsa

_________________________________________________________________________
Address at Contact number ng nagbigay ng pahintulot

____________________________ ___________________________
Pangalan at Lagda ng Testigo Pangalan at Lagda ng Nananaliksik

Disclaimer: This was sent electronically and parents of the patient agreed with was stated above.
Unfortunately, printing of the document was not possible, hence permission was granted via verbal and
electronic (text) means.

15
16