Abstract:Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive, multiorgan disorder with cardinal features of cerebellar ataxia, congenital or early childhood cataracts, psychomotor retardation, and myopathy. Additional features include hypergonadotropic hypogonadism, various skeletal abnormalities and deformities due to muscle weakness, short stature, and strabismus. The neuroradiologic hallmarks are hypoplasia of both the vermis and cerebellar hemispheres. The histopathologic findings include severe cerebellar atrophy and loss of Purkinje and granule cells. The common pathologic findings in muscle biopsy are variation in muscle fiber size, atrophic fibers, fatty replacement, and rimmed vacuole formation. The presence of marked cerebellar atrophy with myopathy distinguishes MSS from another rare syndrome, the congenital cataracts, facial dysmorphism, and neuropathy syndrome (CCFDN). Mutations in the SIL1 gene on chromosome 5q31 were demonstrated to cause MSS, which is caused by homozygous or compound heterozygous. MSS is genetically distinct from congenital cataracts, facial dysmorphism, and neuropathy, which is caused by mutation in the CTDP1 gene on chromosome 18q23; MSS can share some overlapping features with other sundromes, including congenital cataracts, delayed psychomotor development, and ataxia. The major distinguishing clinical features of MSS are the presence of peripheral neuropathy, facial dysmorphism, and microcornea (Lagier-Tourenne et al., 2003). Patients with a subtype of MSS with myoglobinuria and neuropathy have been linked to chromosome 18q23r, and recently a locus for classical MSS has been localized on chromosome 5q31. The importance of myopathy has been determined in this disorder apart from the CNS based disability. Pattern of muscle involvement and degree of its severity have been established. Muscle computed tomography (CT) investigations were carried out in many MSS patients homozygous for markers around the MSS locus on chromosome 5q31. Patients with severe clinical disability showed severe and generalized muscle degeneration. Muscle CT findings in patients with relatively severe clinical picture were characterized by severe involvement of the posterior thoracic and pelvic muscles, and almost all thigh muscles. In the legs, the peronei and posterior compartment muscles were severely degenerated. The group of patients with moderate severity of disease showed the same pattern of involved muscle, albeit with lower degree of muscle degeneration. Patients with MSS linked to chromosome 5q31 have a severe progressive myopathy, the extent of which may remain largely unrecognized because of the CNS involvement. In this case study, two female siblings were reported with typical symptoms of MSS; but however without any cognitive or intellectual deficits and with stable and normal mental development. A review of the literature was performed for understanding of the history and assessment of the disease and possible management and treatment. MSS is genetically heterogeneous, and mutations of SIL1 are often not evident. Consequently, new genes for MSS await discovery and they hold the promise of furthering the mechanistic understanding of the condition, enabling clinically meaningful genetic classification schemes to be designed.
Keywords:Marinesco–Sjoegren syndrome (MSS); SIL1 gene; Bradykinetic movement disorder; Motor neuronopathy; Multisystem disorders; Autophagy; Ataxia; clinical scale; DNA repair; ion channel dysfunction; mitochondrial dysfunction; polyglutamine disorders.
MARINESCO-SJOEGREN SYNDROME: A RETROSPECTIVE EVALUATION OF A RARE ENTITY OF TWO FEMALE SIBLINGS WITH WELL-PRESERVED COGNITIVE MILESTONES AND INTELLECTUAL ABILITIES. REVIEW OF THE LIETRATURE WITH MAIN FOCUS ON MOLECULAR BIOLOGY AND GENETICS
Munthir Al-Zabin, Herbert Wachtermann
International Journal of Novel Research in Life Sciences