Human Disease Model Report: neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter

General Information

Name

neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter

FlyBase ID

FBhh0001654

Disease Ontology Term

neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter

Parent Disease

OMIM

NEURODEVELOPMENTAL DISORDER WITH SPASTICITY, THIN CORPUS CALLOSUM, AND DECREASED BRAIN WHITE MATTER; NEDSCW

Overview

This report describes neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter. The human gene implicated is RPS6KC1, which encodes ribosomal protein S6 kinase C1. There is one moderate-scoring fly ortholog, Dmel\Rps6kc1, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human gene RPS6KC1 has not been introduced into flies.

Ubiquitous RNAi knockdown of Dmel\Rps6kc1 results in a reduction of neuronal density, and a decrease in the number and size of active zones at the larval neuromuscular junction, in impaired locomotor function and climbing ability, and in decreased lifespan. Affected flies also exhibit a decrease in Dmel\mTor expression levels.

[updated Aug. 2026 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter

OMIM report

[NEURODEVELOPMENTAL DISORDER WITH SPASTICITY, THIN CORPUS CALLOSUM, AND DECREASED BRAIN WHITE MATTER; NEDSCW](https://omim.org/entry/621460)

Human gene(s) implicated

[RIBOSOMAL PROTEIN S6 KINASE C1; RPS6KC1](https://omim.org/entry/617517)

Symptoms and phenotype

Neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter (NEDSCW) is an autosomal recessive disorder characterized by mild to moderate global developmental delay with mildly to moderately impaired intellectual development and progressive spasticity of the lower limbs with hyperreflexia. Brain imaging shows thin corpus callosum and reduced white matter volume. Additional more variable features may include dysmorphic facies, seizures, behavioral abnormalities, and scoliosis (Planas-Serra et al., 2025).pubmed:41130203). [from MIM:621460; 2026.08.13]

(OMIM, 2013-)

Genetics

Neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter (NEDSCW) is caused by homozygous or compound heterozygous mutations in the RPS6KC1 gene on chromosome 1q32. [from MIM:621460; 2026.08.13]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

RPS6KC1 is a sphingosine kinase-1 (SPHK1)-binding protein implicated in sphingosine-1-phosphate (SPP)-mediated signaling (Hayashi et al., 2002, pubmed:12077123). [from MIM:617517; 2026.08.13]

(OMIM, 2013-)

External links