Marinesco-Sjögren Syndrome: A Case Report

A 4.5-year-old girl––first child, born full-term to second-degree consanguineous parents, presented with difficulty walking independently. 

Developmental delays were first noticed at six months (inability to hold neck) and by 3.5 years. She had an unsteady, wide-based gait with frequent falls. There were no seizures or hearing issues.

Neurodevelopment: Her development quotient (DQ) was 61%, with significant delays in gross motor (22%) and fine motor (27%) skills. While her language, social, and adaptive skills were normal.

On examination, the child was severely underweight, stunted, and microcephalic. She had bilateral pseudophakia, generalized hypotonia, and proximal muscle weakness. Cerebellar ataxia, scanning speech, pass pointing, and dysdiadochokinesia were present. She did not have tremors.

Differential Diagnosis: Intellectual disability, hypotonia, ataxia, and bilateral cataracts suggested possible diagnoses, including MSS syndrome, congenital cataracts, facial dysmorphism, neuropathy (CCFDN), Infantile-Onset Spinocerebellar Ataxia (IOSCA), muscular dystrophy, Lowe syndrome, or mitochondrial disorders.

Laboratory tests were normal for calcium, magnesium, creatinine phosphokinase, ammonia, thyroid, and parathyroid hormone. Electromyogram and nerve conduction studies were unremarkable. Brain MRI showed diffuse cerebral atrophy, severe vermis hypoplasia, and a prominent fourth ventricle.

Whole exome sequencing (WES) identified a homozygous frameshift c.302_303del (p.Glu101GlyfsTer6) variant at exon 4 in theSIL1 gene, confirming Marinesco-Sjögren syndrome (MSS).

The child was managed with a multidisciplinary approach, focusing on rehabilitative physiotherapy. 

MSS is a rare genetic disorder with infantile onset and significant phenotypic variability. Developmental delay, mental retardation, ataxia, and cataracts should raise suspicion of MSS. The MRI of these patients may show abnormalities like a small cerebellar vermis and pituitary gland. Mutations in the SIL1 gene – on chromosome 5, are detected in 50-60% of patients. Cataract – a defining hallmark, is present in 96% of patients and typically develops around 3.2 years. Other ocular findings––strabismus and nystagmus––are found in 50% of the patients. Clinical diagnosis remains challenging since the condition is detected shortly after birth and much before the ocular symptoms are evident. Treatment emphasizes rehabilitation and genetic counseling, as no cure exists. A detailed exploration of hormonal parameters is necessary to understand the pathophysiological landscape comprehensively.

Source: Malik N, Arif M, Bhatnagar S. Indian pediatrics.:S097475591600667.