Clinical Manifestations and Genetic Insights Into Congenital Myasthenic Syndrome-22 in Pediatric Patients.

BACKGROUND

The study aimed to identify the manifestation of isolated Prolyl endopeptidase-like (PREPL) deficiency in children to aid in diagnosis and early intervention.

METHODS

We performed a retrospective cohort study, including five children genetically confirmed with PREPL gene mutations. Clinical features, genotypes, and treatment responses were analyzed.

RESULTS

The study involved four girls and one boy. The major neuromuscular features were hypotonia and feeding difficulties in the neonatal period. They all had global muscle weakness. Different from typical symptoms of CMS, only one patient had transient unilateral mild ptosis with no obvious fluctuating nature. Minor facial dysmorphism, growth retardation (especially underweight), and significantly delayed motor development were frequently observed. One patient also showed language and cognitive development delay. In addition, two cases had a predominant decrease in insulin-like growth factor 1 at 2.3 and 1.6 years, respectively. The median age at diagnosis was 5 (1-12) months. Eight previously nondescribed mutations were detected among the five patients, in four children with compound heterozygous mutations and one child with homozygous mutations (maternal uniparental disomy). The frameshift mutation site (p. F428fs∗18) was found in two unrelated patients. All patients have received pyridostigmine treatment at median age of 6 (3-14) months. Four cases exhibited significant improvements in motor development.

CONCLUSIONS

Isolated PREPL deficiency is a multisystem disease more than just myasthenia. Early referral to diagnosis is crucial to enable timely initiation of treatment. Pyridostigmine is an effective treatment to improve motor development in most children. Monitoring hormone levels, including insulin-like growth factor 1, can assist in early intervention.