SCIENTIFIC
Cardio-Facio-Cutaneous Syndrome with an Unusual Presentation of Respiratory Failure Requiring Tracheostomy and Long-term Ventilation
AUTHORS : Joseph A . McGuire 1
Saif Al-Qatarneh , MD 2
1
Department of Anesthesiology , West Virginia University School of Medicine
2
Division of Pulmonology , Department of Pediatrics , West Virginia University School of Medicine
ABSTRACT
Cardio-facio-cutaneous ( CFC ) syndrome is a phenotypically diverse disorder that is caused by mutations in the RAS / MEK / ERK signaling pathway , sharing many clinical similarities with Noonan and Costello syndromes . Classic findings of CFC include congenital cardiac anomalies , dysmorphic facial features , dermatological manifestations , and other multisystemic abnormalities . Laryngomalacia , generalized muscle weakness , and hypotonia have been reported phenotypical variants of the disorder . We describe a case of a male newborn with a genetic diagnosis of CFC syndrome who presented with respiratory failure requiring tracheostomy placement and chronic ventilation .
CASE PRESENTATION
A one-month-old boy presented to the emergency department ( ED ) due to respiratory distress and failure to thrive . His past medical history was significant for a prenatal ultrasound that demonstrated nuchal translucency and polyhydramnios . The baby was born via spontaneous vaginal delivery at 35 weeks and 6 days gestation . He had notable respiratory distress shortly after birth , warranting the initiation of continuous positive airway pressure in the neonatal intensive care unit ( NICU ). His physical examination findings upon birth included dysmorphic facial features of low-set ears , recessed chin , short broad nose , wide-spaced eyes , and hypotonia . Throughout the NICU stay , his respiratory status slowly improved . However , a nasogastric ( NG ) tube placement was performed because of difficulty tolerating feeds and failure to thrive . A transthoracic echocardiography showed mild pulmonary valve stenosis , and mild right ventricular hypertrophy . A genetic workup yielded a pathogenic BRAF heterozygous variant on Exon 11 ( c . 1403T > C ), consistent with the diagnosis of cardiofaciocutaneous ( CFC ) syndrome .
On day 24 of life , the patient was discharged from the NICU with 0.5 liters of supplemental oxygen via nasal canula . Shortly after discharge , he had an increased work of breathing and inspiratory stridor that progressed significantly over time and required an ED visit . At presentation , the patient was noted to have severe distress . His respiratory rate was 90 reathes per minute , heart rate was 167 beats per minute , and his blood pressure was 104 / 58 mmHg , with an oxygen saturation of 95 %. Physical examination revealed tachypnea , subcostal retractions , abdominal breathing , and loud stridor with gasping . His skin was dry and scaly with hyperkeratosis . The patient was transferred to a pediatric intensive care unit ( PICU ) and was started on non-invasive ventilation .
An airway evaluation through a bronchoscopy showed an omega-shaped larynx , short aryepiglottic folds , and severe arytenoid cartilage collapse that indicated laryngomalacia and led us to perform a supraglottoplasty . Due to the failure to extubate over multiple attempts , a follow-up airway revision with a bronchoscopy revealed unresolved severe laryngomalacia . Therefore , a tracheostomy was performed . During the post-operative PICU course , the patient continued to have respiratory distress with shallow breathing and an increased respiratory rate . His arterial carbon dioxide levels were elevated ( 55-62 mmHg ), despite continuous pressure ventilation and oxygen flow supplementation . A bi-level ventilation resulted in an improved respiratory status and normalization of the oxyhemoglobin saturation and arterial carbon dioxide levels . Throughout the rest of the hospital course , the patient ’ s vitals remained stable , and with a proper nutritional regimen through a gastric tube feeding , he demonstrated adequate weight gain .
DISCUSSION
CFC syndrome is a rare multi-organ autosomal dominant disorder belonging to a group of syndromes known as the RA- Sopathies , which also includes Noonan syndrome and Costello syndrome . 1 The three disorders are clinically related developmental disorders that have been recently linked to mutations in the RAS / MEK / ERK signaling pathway . 2
The phenotypic variance of CFC syndrome varies widely and is thought to be correlated with specific genotypes . 1 There are a multitude of other symptoms that may accompany the disease . 3 , 4 As the name implies , the syndrome is mainly characterized by congenital cardiac anomalies , dysmorphic facial features , and dermatological manifestations such as dry skin , keratosis pilaris , eczema , and dystrophic nails . 5 Studies have reported lymphatic disorders , 6 neurologic disorders , gastrointestinal dysfunctions , 7 and other manifestations aside from the classic presenting symptoms of CFC syndrome .
Laryngotracheal abnormalities such as laryngomalacia and laryngeal clefts are also seen in CFC ; however , it has been rarely described in young infants who have required tracheostomy because of marked laryngomalacia after failed supraglottoplasty . 8 Global hypotonia is evident upon clinical examination — especially in the newborn period — and is manifested by delayed motor skills , muscle weakness , and decreased muscle bulk . 9 To note ,
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