A Case of Neonate With Silent Expression

A 2.09 kg male infant is born to a primigravida with monochorionic monoamniotic twin gestation at 34 weeks through emergency lower segment cesarean delivery in view of presumed fetal compromise. It was a spontaneous conception from a nonconsanguineous marriage. The birthing parent received folic acid supplementation in the first trimester, and twin reversed arterial perfusion sequence was the antenatal diagnosis with evidence of acardiac amorphous second twin. Subsequent antenatal scans revealed findings of a muscular ventricular septal defect with no signs of hydrops or effusions in the pump twin with normal antenatal doppler. Antenatal steroids were completed prior to delivery.The infant receives routine care at birth and is admitted to the neonatal intensive care unit for low birth weight and prematurity. The infant has transitional respiratory distress, requiring continuous positive airway pressure (CPAP) for 24 hours. Physical examination is significant for a flat forehead with overriding of the parietal and temporal bones over the frontal bone, antimongoloid slant of the eyes, flat philtrum, thin lips, high-arched palate, and a dysmorphic, apathetic facial expression. Limb-length discrepancy is also noted with left developmental dysplasia of the hip and congenital talipes equinovarus of the left foot.On day 2 of life, the infant has 3 episodes of focal seizures. The evaluation for sepsis as well as metabolic profile results, including serum electrolytes, calcium, magnesium levels, ammonia, lactate, and blood gas, are normal. The findings of the fundus examination are normal. The electroencephalogram results are significant for epileptogenic focus in the right frontal lobe. Seizures are controlled with phenobarbital.A repeat sepsis evaluation on the next day is performed, including a lumbar puncture, the results of which are normal, ruling out the possibility of meningitis. Considering the early clinical presentation and negative sepsis markers, encephalitis is not considered, and antivirals are not started.Neonatal strokeCerebral malformationsIntracranial hemorrhageInfectionsA brain magnetic resonance imaging (MRI) scan is initially done on day 3 of life, and the results show no significant abnormality. The infant continues to have decreased activity for 2 days prior to demonstrating clinical improvement. Persistent pooling of secretions, lack of facial expression, absence of nasolabial folds, and decreased horizontal eye movements along with incomplete closure of eyes and absent conjunctival and corneal reflex are noted. In the initial period, the infant was on breathing support (CPAP) and clinical signs were not observed before the episodes of seizures. However, these signs become more evident after the seizure episodes.In view of suspected cranial nerve involvement (fifth, sixth, and seventh nerves) the brain MRI scan (constructive interference in steady state [CISS] sequence) is repeated, which reveals incomplete segmentation of tectal plate and nonvisualized facial colliculi with bilateral absence of abducens and facial nerves and the normally visualized course of other cranial nerves (Figure 1). The MRI findings are suggestive of Moebius syndrome (MBS). The pediatric neurology service is consulted and recommends supportive management. The infant is started on lubricant eye drops to prevent exposure to keratitis. Oro motor stimulation and facial massage are initiated. Phenobarbitone is stopped after 5 days because there are no further seizure episodes. Developmentally supportive care with early intervention measures is advised. The infant is initially started on tube feeding and gradually shifts to spoon and breastfeeding by the day 10 of life. The baby regains birth weight on day 12 of life and is discharged from the hospital on day 14 of life. At the subsequent follow-up visit, the baby is thriving well, but the infant continues to demonstrate the features of sixth and seventh cranial nerve involvement. The infant is periodically followed up as per the unit policy.MBS is a cranial dysinnervation disorder that primarily affects the sixth and seventh cranial nerves. Infants with this condition typically experience difficulties with feeding and vision. Additionally, many patients exhibit involvement of other cranial nerves. While commonly associated anomalies may include orofacial and limb anomalies,1,2 the classic manifestations are ocular and facial palsy. The first case of MBS was described by Von Graefe in 1988. While the inheritance pattern of MBS is predominantly sporadic, some cases are reported to be autosomal dominant, recessive, or X-linked as well.3 This syndrome is more frequently observed in fetuses that are conceived through reproductive technique rather than natural fertilization.4MBS results from a complex interplay of factors including genetic, developmental, and potentially environmental, leading to the dysfunction of cranial nerves. Several theories are postulated including vascular insults during early fetal life that affect cranial nerve development due to disruption of main subclavian artery’s vascular supply. Other theories involve the absence or underdevelopment of the cranial nerve nuclei and genetic mutation that affects the development of the brainstem and cranial nerves. Additionally, maternal use of drugs like cocaine or misoprostol can lead to fetal thrombosis, hemorrhage, or vascular events that contribute to the development of MBS.5,6MBS is a clinical diagnosis with key features such as unilateral or bilateral facial paralysis, feeding difficulties, and atypical eye movements.7 Additional musculoskeletal abnormalities often observed include hand and foot deformities like syndactyly, brachydactyly, as well as pectoralis muscle agenesis. Other clinical signs include a lack of facial expression, drooping of the eyelids, and developmental delays. MBS has also been associated with several other syndromes including Poland syndrome, Pierre Robin sequence, Carey-Fineman-Ziter syndrome, and Klippel-Feil anomaly.Abramson et al7 studied 28 patients with MBS and subdivided the syndrome into 5 anatomic components. They formed the acronym CLUFT (C = cranial nerve, L = lower limb, U = upper limb, F = facial structure, and t = thorax). The CLUFT grading system helps us to evaluate the degree of facial and oral muscle impairment. Each component is graded individually based on clinical features and functionality on a scale from 0 to 3. The scores for each component are summed up to provide a total CLUFT score, which indicates the overall severity of cranial nerve and facial dysfunction in the patient.7The MRI scan is the gold standard for visualizing the brainstem and cranial nerve nuclei to confirm an MBS diagnosis. The most common findings are absent or hypoplastic facial nerve nuclei, brainstem abnormalities, and other cranial nerve nuclei abnormalities. Magnetic resonance angiography is used to rule out vascular abnormalities and malformations. A computed tomography (CT) scan can show calcification in the brainstem and around cranial nerve nuclei. Other findings that are reported on the CT scan are cerebral hypoplasia and fourth ventricle abnormalities.8Management of MBS should have both components of a holistic and individualized approach, including medical management, surgical correction, and educational and psychosocial support. Medical management includes regular neurodevelopmental as well as pediatric neurologic follow-up. Surgical interventions that facilitate rehabilitation can correct or improve orofacial and limb deformities and ophthalmic problems. Important aspects of supportive care include speech therapy, occupational therapy, physical therapy, and psychological support. A multidisciplinary approach is important for awareness and family education to ensure proper follow-up and treatment.A high level of suspicion is necessary to consider a diagnosis of MBS in a newborn exhibiting signs of cranial nerve involvement.Cranial nerve examination is important in cases of neonatal encephalopathy and neonatal seizures.MRI scan with the CISS sequence is important for the diagnosis of MBS with cranial nerve nuclei involvement.The prognosis of MBS can vary depending on the severity of the condition and the associated symptoms.American Board of Pediatrics Neonatal-Perinatal Content SpecificationUnderstand disorders of migration of the central nervous systemKnow the physiology of the nervous system