Marinesco-Sjogren syndrome (MSS) is an autosomal recessive disorder which has been characterized primarily through congenital cataracts, cerebellar ataxia, progressive muscle weakness due to myopathy, and delayed psychomotor development. Other characteristics of MSS involve short stature, hypergonadotrophic hypogonadism, and skeletal deformities due to muscle weakness.
MSS has been allocated to chromosome 5q31 and mutations have been found in SIL1, which is a gene that encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation, and a C-terminal ER retention signal. This protein consists of 461 amino acids and weighs up to 52085 Da, it is necessary for protein translocation and folding in the ER and it functions as a nucleotide exchange factor for the ER luminal chaperone HSPA5.
Karim et al. (2006) studied four affected members of two separate sibships in a consanguineous Egyptian family with Marinesco-Sjogren syndrome. A remarkable feature in this family was the lack of cerebellar ataxia in a 25-year-old male and 19-year-old female who were sibs of the mother of 7- and 9-year-old females with full expression of Marinesco-Sjogren syndrome. The older patients had delayed physical and mental development, mental retardation, progressive muscle weakness, hypotonia of legs, and cataract. The male showed hypogonadism.
Farah et al. (1997) found two brothers affected with Marinesco-Sjogren syndrome (MSS) in a consanguineous Bedouin family. The two brothers were in their twenties and had abnormally short lateral 3 metatarsals, a characteristic that was absent in other healthy family members. They also demonstrated features of hypergonadotropic hypogonadism.
Anazi et al. (2016) studied the feasibility of adopting genomic tools as a first-tier test in the diagnosis of Intellectual Disability (ID). The authors recruited 337 ID affected patients based on IQ scores, delayed speech acquisition and other cognitive developmental delays. They were subjected to molecular karyotyping, exome sequencing and a multi-gene panel comprised of genes associated with neuro-genetic diseases. Genomic tools were found to have a higher diagnostic yield than standard clinical evaluations (58% vs 16%). The tests helped uncover a homozygous mutation (c.1030-9G>A) in the SIL1 gene of one patient, suggesting a diagnosis of Marinesco–Sjogren syndrome. However, it was noted that the patient’s MRI exhibited features typical of Joubert syndrome.
Nair et al. (2016) described a 12-year-old Emirati male, from a consanguineous family, presenting with developmental and speech delay, ataxia and bilateral cataracts. The patient also suffered from intention tremor, dysmetria, dysdiadochokinesia, pectus carinatum, mild kyphosis, bilateral clinodactyly of the fifth fingers and flat feet. His cataracts had been surgically corrected and he had undergone an orchidopexy for an undescended left testis. Brain imaging studies revealed cerebellar atrophy with a dilated fourth ventricle. Subtle facial dysmorphia included bushy eyebrows and a flat mid face with a high arched palate. Based on a tentative diagnosis of MSS, the patient’s SIL1 gene was analyzed thus uncovering a homozygous c.-197_90delinsCTGTACTTTCTCAGTTCACT mutation. Both parents were found to be heterozygous for the indel mutation. Further, the variant was not found in the ExAC browser or the GALAXCTM Allele Frequency Database.
To contribute with your findings to the content of this record, please fill the CTGA Database Information Submission Form and email it, along with supportive documents, to firstname.lastname@example.org.