In other species: sheep

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 257320 (trait) , 600514 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0009760: Norman-Roberts syndrome

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2023

Cross-species summary: Renamed from 'Lissencephaly and cerebellar hypoplasia' to 'Lissencephaly and cerebellar hypoplasia, RELN-related' [22/09/2023]

Species-specific name: Cerebellar hypoplasia

Species-specific description: References to other forms of lissencephaly were previously listed here but have been moved to OMIA:002771-9615 : Lissencephaly, generic in Canis lupus familiaris [22/09/2023]

Molecular basis: Littlejohn et al. (2023) "describe a genetic investigation of cerebellar hypoplasia in White Swiss Shepherd dogs, where two affected puppies were identified from a litter with a recent common ancestor on both sides of their pedigree. Whole genome sequencing was conducted for 10 dogs in this family ... [and identified] a frameshift-deletion of the Reelin (RELN) gene (p.Val947*)."

Clinical features: Littlejohn et al. (2023): Two affected White Swiss Shepherd "puppies were born clinically normal ... . Both [cerebellar hypoplasia] CH-affected puppies failed to gain weight and developed progressive ataxia from around 2 weeks of age. The puppies had difficulty standing, could not walk in a straight line, had a good suckle reflex but had difficulty latching on to the teat. The puppies had no spontaneous or positional nystagmus, had a normal pupillary light reflex, lacked a menace reflex (normal for age) and segmental spinal reflexes were intact. ... the puppies were euthanised at 4 weeks of age ... ."

Pathology: Littlejohn et al. (2023): "Autopsy [of two affected White Swiss Shepherd puppies] revealed anatomical abnormalities in the brains of both affected puppies, with both animals showing severe CH with lissencephaly ... and moderate internal hydrocephalus with distended lateral and fourth ventricles. ... In both puppies the cerebellum lacked cerebellar folia. ... Microscopically, the normal layered structure ... of the cerebellum was disorganised ... and the molecular and granular layers were thin, with the granular layer of irregular thickness ... and often forming islands of cells ... . Purkinje cells were scattered throughout all layers ... . Vascular structures were prominent. The cerebrum lacked sulci and gyri (agyria) and the white matter was thinned. The cerebral cortex was disorganised with increased thickness of the cortical laminae and neuronal cell bodies that were not vertically aligned."

Breed: White Swiss Shepherd Dog (Dog) (VBO_0201423).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: