Title: Neonatal Presentation of Congenital Central Hypoventilation
1 2Neonatal Presentation of Congenital Central
Hypoventilation Syndrome
Y. K. Abu-Osba, Miqdad H. Mukahhal Neonatal
Intensive Care Unit Jordan Hospital, Amman,
Jordan
3Presentation outline
- Introduction.
- Definition and diagnosis of CCHS.
- Case presentation.
- Summary.
- Conclusions.
- Recommendations.
4Neonatal Presentation of CCHS Background -1
- The appropriate nomenclature for the disorder
known as Ondine curse is congenital central
hypoventilation syndrome (CCHS). The literary
misnomer "Ondine's curse" has been used in prior
literature. - In the story of Ondine, a German folk epic, the
nymph Ondine falls in love with a mortal. When
the mortal is unfaithful to the nymph, the king
of the nymphs places a curse on the mortal. The
king's curse makes the mortal responsible for
remembering to perform all bodily functions, even
those that occur automatically, such as
breathing. When the mortal falls asleep, he
"forgets" to breathe and dies. - Because Ondine did not actually curse the mortal
(it was her king) and the approximately 300
children worldwide with CCHS do not forget to
breathe, the term Ondine's curse is a misnomer
and should be avoided.
5Neonatal Presentation of CCHS Background -2
-
- Classic congenital central hypoventilation
syndrome (CCHS) is characterized by adequate
ventilation while the affected individual is
awake and by hypoventilation with normal
respiratory rates and shallow breathing during
sleep more severely affected individuals
hypoventilate when both awake and asleep. -
- Children with CCHS often have physiologic and
anatomic manifestations of a generalized
autonomic nervous system dysfunction/dysregulation
(ANSD) a subset have altered development of
neural crest-derived structures (i.e.,
Hirschsprung disease) and tumors of neural crest
origin including neuroblastoma, ganglioneuroma,
and ganglioneuroblastoma. -
6Neonatal Presentation of CCHS Background -3
- Recently, it has been recognized that some
individuals with nocturnal alveolar
hypoventilation, features of ANSD, and a
polyalanine expansion mutation in PHOX2B
characteristic of CCHS do not present until
childhood or adulthood. - Its inherited in an autosomal dominant matter
with 5 of them having an asymptomatic parent who
has somatic mosaicism for a PHOX2B mutation. - Many individuals with CCHS who have been
successfully ventilated are now in their 20s,
suggesting the potential for a normal life span.
7Neonatal Presentation of CCHS Background -4
- CCHS is diagnosed in individuals with the
following - Hypoventilation with absent or negligible
ventilatory sensitivity to hypercarbia and absent
or variable ventilatory sensitivity to hypoxemia - Generally adequate ventilation while awake, but
hypoventilation with normal respiratory rate and
shallow breathing (diminished tidal volume)
during sleep - Hypoventilation both while awake and asleep
- Absent perception of asphyxia (i.e., absent
behavioral awareness of hypercarbia and
hypoxemia) and absent arousal - No evidence of primary neuromuscular, lung, or
cardiac disease or identifiable brain stem lesion
that might account for the constellation of
symptoms
8Neonatal Presentation of CCHS Case report
Initial presentation
- Rania and Abdallah were born by C/S after 36
weeks of pregnancy (IVF-due to paternal history
of Immotile Cilia Syndrome). - Their birth weight was 2.44 kg and 2.41 kg ,
Apgar score was 5/6/7 at 1/5/10 minutes
respectively. - Naloxone was given during resuscitation due to
poor respiratory effort. - They were sent to nursery and observed closely
after starting them on O2 by head box due to poor
respiratory effort. Rest of their physical
examination was normal.
9Neonatal Presentation of CCHS Case report
- ABGs at one hour of age
- Abd PH 7.004 , PaCO2 74.9 mmHg ,PaO2 107
mmHg HCO3 18.4 mmol/l,BE-12.8 . - Ran PH 7.044, PaCO2 69, PaO2 68, HCO3
18,BE -12. - They were admitted to NICU with poor respiratory
effort and hypopnea resulting in cyanosis and CO2
retention . - The patients were started on Nasal CPAP trial,
ABGs after one hour showed - Abd PH 7.00 , PaCO2 106.2 mmHg,PaO2 51.5
mmHg , HCO325.6 mmol/l,BE -8.6.
10Neonatal Presentation of CCHS Case report
- Ran PH 7.08,PaCO2 86,PaO2 87,HCO3
25,BE-5. - The patients were intubated started on
mechanical ventilation (SIPPV), VBGs after one
hour of ventilation - Abd PH 7.24 , PaCO2 36.3mmHg, PaO2
40.5mmHg , HCO3 15.2mmol/l, BE -11. - Ran PH 7.44, PaCO2 20, PaO2 89, HCO3 13,
BE-11. - Several trials of CPAP ventilation failed due to
hypoponea prolonged apnea, blood gases were
done as needed. - Aminophylline intravenously was given at maximum
doses it was stopped when caffeine was given on
the request of the family. - They received Intravenous Antibiotics for 5 days,
which were discontinued after ruling out sepsis.
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12Neonatal Presentation of CCHS Case report
- Investigations
- Chest X ray No signs of RDS, normal lung fields.
- Cranial ultrasonography normal. No evidence of
ICH. - Abdominal Ultrasound normal.
- Echocardiogram normal cardiac structure,
dextroposition of the heart with normal axis , no
evidence of pulmonary hypertension. - Blood and urine cultures negative.
- CBC normal for age.
- Kidney Function Test normal
- Serum immunoglobulin levels normal for age.
-
13Neonatal Presentation of CCHS Case report
- Metabolic Screen urine serum Amino acids
unremarkable. - Serum ammonia lactate normal levels
- Carnitin blood level was low, Subsequent levels
were normal. - Brain CT scan revealed assymetry in the lateral
ventricles in the girl only which was interpreted
by neurosurgeons as normal variation. -
14Neonatal Presentation of CCHS Case report
- Presentation and clinical course is not
consistent with surfactant deficiency, pneumonia,
sepsis, metabolic disorder, ICH, or PPHN, which
had been ruled out by laboratory, and
radiological investigation and clinical course. - Our differential diagnosis was either CCHS or a
new presentation for Primary Immotile cilia
syndrome / dyskinesia. -
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17Neonatal Presentation of CCHS Hospital Course
- During their stay in NICU,the twin were started
on N/G feeding and increased gradually which was
tolerated without any problems. - Cardiology evaluation normal echocardiography
and normal 24 hr holter monitoring without any
arrythmias. - Neurology evaluation no clinical neurological
abnormalities detected.
18Neonatal Presentation of CCHS Hospital Course
- Ophthalmology consultation bilateral retinal
examination showed immature retina Zone II III
with no retinal pigmentation. No ROP. Follow up
exams were normal. - Infectious dis. consultant was following them
during their hospitalization with routine
cultures and appropriate antibiotics when
indicated. - Consultations with centers abroad( England and
USA) for definite diagnosis.
19Neonatal Presentation of CCHS Hospital Course
- Recurrent trials of VERY slow weaning from
mechanical ventilation failed with acidosis and
hypercarbia. - Recurrent reintubation became difficult and done
by expert anesthetists with time. - Muscle biopsies were taken from both babies at
the age of 3 months and blood samples from
parents were all sent to Rush University and
Medical Center . Results confirmed the diagnosis
of CCHS in the twin ( Positive for PHOX2B
gene-20/27). - The father had a CCHS polyalanine repeat
expansion mutation(20/27) suggesting somatic
mosaicism without clinical symptoms. - By that time the family started to accept the
idea of tracheostomy and home ventilators for the
twin.
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23Neonatal Presentation of CCHS Hospital Course
- Treatment Modalities
- Tracheostomy.
- Gastrostomy.
- Home ventilation.
- Diaphragmatic pacing.
24Neonatal Presentation of CCHS Hospital Course
- At the age of 4 months, tracheostomy was done
for them by pediatric surgeon. Postoperatively
tracheostomy tubes were out and they
were reintubated again. During this attack,
Abdullah suffered from asphyxia that lead to
recurrent seizures and eventually declared brain
dead by flat EEG record and abscent brainstem
reflexes. - Abdullah died on 30/7/2007 at the age of five
months. - Rania was put on mechanical ventilator by ETT
and did well afterwards. - Rania was transferred to another hospital for
long term management. Currently shes 9 months
old on tracheostomy tube and mechanical
ventilator and feeding by gastrostomy.
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26Neonatal Presentation of CCHS Summary
- To our knowledge we report for the first time the
clinical presentation of a dizygotic twin with
PHOX2B Positive CCHS. Symptoms were severe since
birth and persisted during awakeness and sleep
and didnt improve with age. - They didnt have any manifestation of ANSD.
- The father had the gene which is known to be
autosomal dominant without any clinical
manifestations apart from his disease( PCDS). -
27Neonatal Presentation of CCHS Conclusions
- CCHS is underestimated to be affecting only 300
children in the world. - High index of suspicion is the most important
factor to give these babies the best survival
with less morbidity. - Early diagnosis minimize health care cost and
exposure to asphyxia. - Mortality is mainly due to acute or chronic
asphyxia and their sequale ( neurological and
pulmonary).
28Neonatal Presentation of CCHS Recommendations
- Establishing referral centers for long term
followup for such patients is important. - Prenatal diagnosis is possible if mutation is
identified. - Increase awareness of CCHS since rarity of the
disease makes it difficult for practitionors to
see cases and diagnose them easily. - Collaboration with the Arab pediatricians to
increase awareness to rare diseases through
U.A.P.
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