Intellectual disability (ID) is a neurodevelopmental disorder resulting in reduced intelligent function, impaired learning ability and poor social interactions. ID is a complex disorder and in many cases have an underlying genetic cause. ID is further classified into syndromic and non-syndromic ID based on the clinical presentation in the patient. Patients with genetic mutation in the LINS1 gene belong to non-syndromic ID, where ID is the sole clinical feature and there are no comorbidities.
Generally, patients with LINS1 mutations have a normal development until 2-3 years of age. Thereafter, there is a gradual deterioration of psychomotor development. The other commonly observed features include facial dysmorphism, dystonic gait, autistic features, behavioral issues and hyperactivity. Features like flat nasal bridge, upturned nose, large ears, and long slender fingers are observed in some patients.
ID has a prevalence of ~1% in the general population worldwide. It is estimated to affect a higher proportion of males, children/adolescents and people from low-middle income countries. Autosomal recessive form of ID is frequent in some parts of the world including India where consanguineous marriages are common.
More than 40 candidate genes have been identified to be associated with non-syndromic autosomal recessive ID. LINS1 gene is one such candidate gene, which was first identified in the year 2011 by Najmabadi et al. in 4 siblings with ID, born to a consanguineous couple. Till date, 16 patients have been reported with a pathogenic disease causing variant in the LINS1 gene.
The mode of inheritance is autosomal recessive. Thus, parents of an affected child are presumed to be heterozygous (carrier) for the variant in the LINS1 gene. Hence, molecular testing is recommended in the parents to confirm the heterozygous status. If parental carrier status is confirmed, each sib of the affected child has a 25% chance of being affected, 50% chance of being an asymptomatic heterozygote/carrier and 25% chance of inheriting neither of the pathogenic variants.
Heterozygotes or carriers are asymptomatic and do not develop any clinical manifestations of the disease.
LINS1