No abstract

A full-term female newborn was transferred to our neonatal intensive care unit (NICU) on day two of life for hypotonia. Physical examination was significant for overriding sutures, displaced small anterior fontanelle, axial hypotonia, extremity hypertonia, and slow deep tendon reflexes. She was also noted to have stridor with crying but had unlabored breathing without oxygen requirements and a normal heart examination. A brain magnetic resonance imaging (MRI) showed a large cisterna magna and cerebellar hypoplasia with the majority of the cerebellar vermis present, suggesting a possible Dandy-Walker variant (cerebellar vermis hypoplasia). Head computed tomography showed areas of close approximation of coronal sutures and no synostosis. During the NICU stay, our patient was evaluated by Pediatric Neurology who recommended a chromosomal microarray which returned normal. The patient also had some difficulty feeding initially, but she was able to feed efficiently and gain weight by the time of discharge.After discharge from NICU, her neurological status steadily declined, resulting in poor motor function and poor suck despite regular physical therapy, occupational therapy, and speech therapy. By three months of age, she developed failure to thrive and was admitted to the hospital for evaluation of the cause. Her neurological examination showed worsening of her axial hypotonia with very little movement in the upper extremities and hypertonia in the lower extremities. She had a weak suck with the inability to form a good seal on the nipple. A new heart murmur was noted and an echocardiogram showed a moderate-to-large atrial septal defect. A modified barium swallow study showed severe dysphagia for which she required gastrostomy tube placement for feeding. At follow-up with Neurology, she was noted to have progressive microcephaly, profound hypotonia, areflexia, and nystagmus. A second MRI showed worsening atrophy and increasing ventriculomegaly. By nine months of age, she developed respiratory failure, required a tracheostomy, and remained ventilator-dependent.Genetics was then consulted and recommended a brain malformation genetic panel. The patient was found to be heterozygous for two pathogenic variants in the EXOSC3 gene: c.155delC and D132A, which is consistent with a diagnosis of autosomal recessive pontocerebellar hypoplasia (PCH) type 1B. The mother was found to be a heterozygous carrier of the c.155delC pathogenic variant, while the father was a heterozygous carrier for the D132A variant, which confirms that the two variants are present on opposite alleles.PCH describes a rare group of 11 neurodegenerative disorders that are typically seen prenatally or shortly after birth. PCH1 is characterized as a combination of PCH and spinal muscular atrophy, with patients presenting with muscle weakness and global developmental delay. An increased understanding of PCH1 will lead to better care and counseling for patients and families.