Spinal Muscular Atrophy and Communicating Hydrocephalus: A Novel or a Well-Established Rare Association?

Spinal muscular atrophy (SMA) is a genetic progressive neuromuscular disease characterized by loss of motor neurons, which is linked to mutation of the survival motor neuron-1 gene. Saudi Arabia has a higher than the worldwide prevalence of the disease, estimated to be 4.42/100,000 cases. Association of spinal muscular atrophy with tetraventricular hydrocephalus secondary to Blake's pouch cyst have rarely been reported. Herein, we report a rare case of genetically confirmed type I spinal muscular atrophy accompanied by communicating hydrocephalus with atypical Blake's pouch cyst. Further studies are needed to confirm the exact genetic correlation.

Neuronal ceroid lipofuscinoses type 8: Expanding genotype/phenotype diversity-first report from Saudi Arabia.

Neuronal ceroid lipofuscinoses (NCLs) are the most common group of neurodegenerative diseases that presents in childhood and are characterized by seizures and progressive neurological deterioration, which results in dementia, ataxia, visual failure, and various forms of abnormal movement. The most common form of neuronal ceroid lipofuscinoses is late infantile (LI-NCL), in association with the genes CLN2, CLN5, CLN6, and CLN8. We report the cases of neuronal ceroid lipofuscinoses type 8 in 3 patients from 2 unrelated families, which was confirmed by molecular testing in 2 of them. Multiple spontaneous abortions, early death, and early onset of motor disability were observed in our cases, reflecting a possible association of NCL 8 with other unrecognized neurodegenerative diseases. Our results expand the genotypic/phenotypic background of variant late Infantile-NCL in Arabic ethnicity.

Neurological expression of an inherited translocation of chromosomal 1 and 7.

An unbalanced translocation of chromosome 1 and 7 (t[1;7]) associated with neurological phenotype and brain malformation has rarely been reported. This clinical report describes 3 siblings with brain malformations and a 13.5 Mb duplication of 1q42.3q44, and a 7.6 Mb duplication of 7q36.1q36.3 detected by array comparative genomic hybridization. This unbalanced t(1;7) was found to be inherited from a balanced translocation from the mother. All the patients presented with hypotonia, microcephaly, developmental delay, seizures, abnormal corpus callosum and abnormal cerebellum.

Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures.

Dominant gain-of-function mutations of the KCNMA1 gene, encoding the pore-forming subunit of the large conductance voltage- and Ca2+-activated K+ channel, have been described in a few patients with the syndrome of epilepsy, paroxysmal dyskinesias and developmental delay. In this report, we describe the loss-of-function phenotype of this newly described disease gene. In two siblings from a consanguineous family with epilepsy, developmental delay and severe cerebellar atrophy, combined exome/autozygome analysis identified a homozygous frameshift duplication in KCNMA1 (c.2026dupT; p. (Tyr676 Leufs*7)) in both children. Our report defines a novel autosomal recessive KCNMA1-related epileptic phenotype that encompasses cerebellar atrophy without paroxysmal dyskinesia, and highlights the sensitivity of the developing brain to both increased and decreased activity of the KCNMA1-encoded channels.