Dr. Terencia, Dr. Sajith Kesavan, Dr. C Jayakumar
Dept of Pediatrics
AIMS, KOCHI
Two years old male child presented with temper tantrums, feeling of loneliness, sleep disturbances and nightmares.
Parents had noticed these symptoms after birth of younger sibling and thought to be due to sibling rivalry
Tab Escitalopram started from an our side health care was without any notable benefit . Child started having increased intake of food and weight gain of 7 kg over a period of 1 month.
Parents had also noticed squint in the left eye one month back.
He also started developing palpitation and discomfort during sleep after which he was immediately rushed to local hospital. He had one episode of? seizure at local hospital and was given Fosphenytoin and needed intubation for respiratory failure.
MRI, EEG, Fundus ,CSF study done was Normal. 3rd day of admission in the local hospital, child had desaturation with Asystole – was given CPR and revived. Child was started on IVIG with a Suspicion of Autoimmune encephalitis. Child was incidentally noted to have hypertension (129/76 m hg), was started on Nifedipine. Patient was referred to AIMS for further management.
Birth History : 2nd child of 4th degree consanguinity
Antenatal history : h/o GDM
Natal history: Term, LSCS, Infant of diabetic mother, B.wt – 3.9 kg, CIAB,
Post natal history: uneventful
Developmental history: Age appropriate milestones attained
Immunized upto age
Nil significant family history
On admission, Child was alert and active
Vitals:T-98F, HR-138b/min, RR-28b/min, Spo2-97%RA, BP-112/88mmhg
Anthropometry:
Wt -22.6 kgs (>97th percentile)
Us : 56 Ls : 42 Ratio : 1:3
Ht – 96 cms (50-90th percentile)
BMI- 24 kg/m2 Hc – 49cms
No dysmorphic facies
Systemic Examination :
CVS – S1 S2 +, no murmur
P/a- soft , non tender
CNS – intubated , sedated and paralyzed
RS – NVBS /AEBE
Differential Diagnosis-
1.Congenital central hypoventilation syndrome (CCHS)
2. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysfunction (ROHHAD)
3. Late-onset central hypoventilation syndrome (LO-CHS)
Child was intubated at the time of admission and was sedated and paralyzed . Child was continued on ventilatory support , Initial blood investigation showed normal counts(TC-7.64( K/uL ), N-39%, L—44%, Hb-12.4g/dl, Plt-292- ( K/uL) with elevated inflammatory markers(CRP- 82.07mg/L) . Auto immune encephalitis panel, EEG and CSF study was normal. Child was initially on ventilator. Sedations were gradually tapered, and child was observed when awake. Even while on ventilator, child had episodes of desaturation and bradycardia with apnea. Hence, child was extubated to BIPAP. Transcutaneous oxy-capnomtery monitoring was done, which showed pco2 > 70 and spo2 < 88 while child is asleep on room air and normalised with bipap . Child was gradually weaned to BIPAP only when the child is asleep. Bystanders have been counselled about the need for BIPAP for the child during sleep.
Child was noticed to have BP of 180/100 ( > 99 the centile ) and was started on labetalol infusion and gradually tapered and stopped. Three antihypertensives were added ( alpha blocker , beta blocker and ACE inhibitors ) . TFT done showed hypothyroidism and was started on T. Thyronorm . Prolactin levels were mild elevated and other parameters cortisol and ACTH sent was normal . As BP was high associated with the other symptoms, neural crest tumor was suspected and was evaluated . Metanephrins and Normetanephrins in blood were elevated . Screening USG abdomen was done which showed a hypoechoic lesion ?originating from neural crest cell in aortocaval area. Confirmatory diagnosis was made MRI abdomen and DOTA-PET scan. Pediatric Surgery consultation was sought and Child was taken up for surgery and the soft tissue lesion was completely excised .The sample was sent for HPE and Morphology was suggestive of Ganglioneuroblastoma, intermixed (Schwannian stroma rich).
Medical oncology consultation was sought and was advised to do n-myc gene amplification and to start chemotherapy. After excision of the lesion , child was initially monitored in the PICU and his BP still contunued to be high . Once child was stable was shifted out to ward and still requiring multiple antinhypertensives ( ACE inhibitors , alpha blocker and beta blocker). A multidisciplinary care meet was conducted and the case was extensively discussed and a decision of giving rituximab was made. Rituximab was planned at 750 mg/m2 2 doses 14 days apart . Child already recieved the first dose and is advised to review for the 2nd dose. Pertaining to the symptoms and diagnostic evaluation child was diagnosed with ROHHAD syndrome and was discharged with stable vitals after advising the parents about the necessity of close follow up.
Rapid onset obesity with hypoventilation and hyperphagia ,autonomic dysfunction
ROHHAD(NET) usually presents in early childhood with rapid weight gain (mean 3.1 years), followed hypothalamic dysfunction (4.0 years), autonomic dysregulation (4.9 years), and lastly, central hypoventilation (5.3 years, or about 2 years after the initial rapid-onset obesity). Up to 56 percent can have neural crest tumors, 70 percent of which were diagnosed within two years of initial rapid weight gain.
ROHHAD(NET) syndrome usually presents in early childhood with the following sequence of symptoms
●Rapid and dramatic gain in weight but not height (mean 3.1 years)
●Endocrinologic disorders, including hypothalamic dysfunction (4.0 years), and autonomic dysregulation (4.9 years)
●Lastly, central hypoventilation (5.3 years, or about 2 years after the initial rapid-onset obesity)
The first few years of life may be quite normal. The excessive weight gain is usually the first feature, and is often very rapidand associated with hyperphagia. This is followed a variety of associated abnormalities in the hypothalamic-pituitary function axis including Cushing-like features, growth hormone deficiency, precocious puberty, hyperprolactinemia, central hypothyroidism, and/or hypernatremia with or without arginine vasopressin deficiency. Autonomic dysregulation includes temperature dysregulation, eye abnormalities, intestinal dysmotility, decreased pain sensation, and/or bradycardia.
Affected children may have behavioral issues, which may be severe, developmental delay, and/or seizures (perhaps triggered hypoxemia or electrolyte imbalance). A high mortality rate is reported. Tumors of neural crest origin (ganglioneuromas and ganglioneuroblastomas) are eventually diagnosed in approximately 50 percent of cases, with most (70 percent) diagnosed within two years of initial rapid weight gain. Suggested evaluation for these tumors includes initial computerized tomography (CT) or magnetic resonance imaging (MRI) of the chest and abdomen. If these are negative, annual screening with chest radiography, adrenal ultrasonography, and urine catecholamines has been suggested.
The breathing disorder may include OSA and mechanical effects of obesity. The central hypoventilation may become more apparent after the obstructive component is treated. The central hypoventilation also may increase over time.
Take over message-
As for other disorders of ventilatory control, children with ROHHAD(NET) fail to have symptoms in response to hypoxemia or hypercarbia, which might be induced routine daily activities or acute respiratory illnesses. Therefore, it is important to perform periodic evaluations of their response to a ventilatory challenge (eg, exercise). Some children will require both daytime and nighttime home monitoring. Like patients with CCHS, children with ROHHAD(NET) have a complex, life-threatening disorder that requires multidisciplinary support, evaluation, and monitoring.