Intellectual Developmental Disorder, Autosomal Recessive 70

A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-70 (MRT70) is caused by homozygous mutation in the RSRC1 gene (613352) on chromosome 3q25.

Description

MRT70 is characterized primarily by impaired intellectual development. Mild facial dysmorphism, febrile seizures, and behavioral abnormalities have been reported in some patients (Maddirevula et al., 2018; Perez et al., 2018).

Clinical Features

Maddirevula et al. (2018) described 3 affected children from a consanguineous Malaysian family with cognitive impairment, no dysmorphic features, and normal brain MRIs. One sib was reported to have had febrile seizures.

Perez et al. (2018) described a consanguineous Bedouin kindred with 5 children who presented with apparently autosomal recessive severe global developmental delay with no regression, impaired intellectual development with speech delay, aberrant behavior, and mild generalized hypotonia. All patients had mild to moderate intellectual disability with walking at age 3 to 4 years and verbal expression of only a few single words even in adolescence. These patients had mild facial dysmorphisms described as a broad nasal bridge, slight hypertelorism, and retrognathia with an open mouth and drooling. All children had febrile seizures during childhood, and one developed focal seizures with impaired awareness that occasionally progressed to bilateral tonic-clonic seizures that were effectively treated with valproic acid. While all affected individuals had deficits in fine motor skills and incontinence, none had abnormalities in coordination. Behavioral abnormalities included temper tantrums, self-harm infliction, and attention deficit hyperactivity disorder (ADHD). One of the 5 sibs had autistic features. The remainder of physical and neurologic exams, ophthalmologic and hearing tests, and brain MRIs were normal.

Inheritance

The transmission pattern of MRT70 in the families reported by Maddirevula et al. (2018) and Perez et al. (2018) was consistent with autosomal recessive inheritance.

Molecular Genetics

Maddirevula et al. (2018) reported 3 sibs with MRT70 with a homozygous nonsense mutation in the RSRC1 gene (R90X; 613352.0001). Perez et al. (2018) reported 5 sibs with MRT70 with a homozygous nonsense mutation in the RSRC1 gene (R69X; 613352.0002).