Prader-Willi Syndrome (PWS) is a multisystemic disorder characterized by dysmorphic facies, hypotonia, developmental delay, cognitive impairment, hypogonadism, and obesity. It is caused by the absence of expression of paternally derived genes on chromosome 15. Here, we report the diagnostic journey of a case with severe neonatal hypotonia. A neonatal patient was referred for the prediagnosis of spinal muscular atrophy (SMA). During the SMA Multiplex Ligation-dependent Probe Amplification (MLPA) analysis, a diminished signal of a reference probe on the 15q11.2 was revealed. Later, it was confirmed that she had a deletion confined to 15q11.2-q13.1, with a methylation pattern compatible with PWS. Since hypotonia might be the only finding in newborns with PWS, this case was presented to emphasize the importance of a comprehensive approach to such patients.

Objectives: This study aimed to detect the presence of mutations in the spastin (SPG4) and paraplegin (SPG7) genes in patients with primary progressive multiple sclerosis (PPMS) to determine the role of hereditary spastic paraplegia (HSP) genes on the susceptibility to PPMS, clinical course, and severity and to reveal its potential role on motor pathways leading to spastic paraparesis clinic. Patients and methods: The descriptive study was conducted with 25 patients with PPMS. The patients were divided into two groups: those presenting with (n=16; 8 males, 8 females; mean age: 47.2±8.4 years; range, 32 to 58 years) and without (n=9; 5 males, 4 females; mean age: 42.8±5.8 years; range, 34 to 49 years) spastic paraparesis. The SPG4 and SPG7 genes from the purified DNAs, which were isolated from blood samples, were sequenced to include all exons and introns. The variations detected as a result of the analysis were evaluated in terms of the suitability of the reading parameters. The frequency of variants in populations and the number of homozygous variants in individuals were analyzed with the gnomAD (Genome Aggregation Database). Of the detected variants, only pathogenic and possibly pathogenic variants that could be clinically associated were reported. Results: In the genotyping of the two groups with PPMS, both with and without spastic paraparesis, no pathogenic or probable pathogenic variant was observed in terms of SPG4 and SPG7 genes. Conclusion: We found no evidence that the SPG4 and SPG7 genes were involved in the pathogenesis, clinical course, and severity of PPMS. However, the question of what kind of effects these genes have on susceptibility to multiple sclerosis and the course remains unclear.

X Chromosome Pericentric Inversion: Report of a Case with 46,X,inv(X)(p11.2q26) and a Mini-Review of the Literature - Gazi Medical Journal