Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases. Homozygous p.G31A/EXOSC3 mutation was identified in 14 Roma patients, representing three fourths of all our SMN1-negative Roma SMA cases. The phenotype of the p.G31A/EXOSC3 homozygotes was compared to the clinical presentation of all reported to date genetically verified PCH1 cases. Signs of antenatal onset of disease present at birth were common in all PCH1 sub-types except in the homozygous p.D132A/EXOSC3 patients. The PCH1sub-types with early death (between ages 1 day and 17 months), seen in patients with p.G31A/EXOSC3 or SLC25A46 mutations have a SMA type 1-like clinical presentation but with global developmental delay, visual and hearing impairment, with or without microcephaly, nystagmus and optic atrophy. Mutations with milder presentation (homozygous p.D132A/EXOSC3 or VRK1) may display additionally signs of upper motor neuron impairment, dystonia or ataxia and die at age between 5 and 18 years. Other EXOSC3 mutations and EXOSC8 cases are intermediate - SMA type 1-like presentation, spasticity (mostly in EXOSC8) and death between 3 months and 5 years. There is no correlation between neurological onset and duration of life. We add marble-like skin and congenital laryngeal stridor as features of PCH1. We show that imaging signs of cerebellar and pontine hypoplasia may be missing early in infancy. EMG signs of anterior horn neuronopathy may be missing in PCH1 patients with SLC25A46 mutations. Thus, there is considerable phenotypic variability in PCH1, with some cases being more SMA-like, than PCH-like. Detailed clinical evaluation and ethnicity background may guide genetic testing and subsequent genetic counseling.

Gastroesophageal reflux in children with cystic fibrosis.

The aim of the study is to reveal the frequency of gastroesophageal reflux /GER/ in children with cystic fibrosis /CF/ and the possibilities of GER's management. Twelve children with CF were monitored for GER by 24-hour pH monitoring of the distal part of the oesophagus, according to the instructions of ESPGAN with Digitrapper MK III, at the time of clinical remission of pulmonary involvement. All patients with diagnosed GER were treated with 10 mg. Cisapride an hour after dinner. GER was proven in 7 children older than 6 years, only while asleep and with no correlation with the time of inhalations. Treatment for GER was safe and effective.

Peptic esophageal stricture in children.

INTRODUCTION: Peptic esophageal stricture as a complication of gastroesophageal reflux disease (GERD) occurs in 5% of the affected children. MATERIAL AND METHODS: Case histories of 6 children treated successfully in the Department of Pediatrics and Clinic of Pediatric Surgery were studied. The diagnosis in each case was based on clinical symptoms (vomiting leading to hypothrophy, hematemesis, and anemia), and esophagoscopy, esophageal pH-metry (according to ESPGAN recommendations), and contrast X-ray examination. After evaluation medical treatment was applied in 3 and bougienage with a hard bougie in 6 patients. Because of failure of this treatment Nissen fundoplication and postoperative bougienage were performed in all patients. RESULTS: In all surgically treated patients complete recovery without postoperative complications was achieved. DISCUSSION: The authors give interpretation of the pathogenesis and outline the primary symptoms of the disease. Terms of performance and reliability of the instrumental methods of diagnosing are discussed. The experience in treatment of peptic esophageal stricture in children is presented. CONCLUSIONS: Medical treatment combined with bougienage yields poor results in peptic esophageal stricture and Nissen fundoplication appears to be the treatment of choice.