Motor Development Disability in Children Linked To Loss of Gene Function

Motor Development Disability in Children Linked To Loss of Gene Function

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Highlights:
  • A research team from Cincinnati Children's Hospital Medical Center and City University of New York School of Medicine identified a probable cause of motor development disability
  • The loss of function of 2 genes were found to affect the Bax/Bak signaling pathway
  • This results in the motor development disability among children, even though their intellectual ability might be average or above average
Motor development disabilities can affect the quality of life of a patient and a study conducted by a research team from City University of New York School of Medicine and Cincinnati Children's Hospital Medical Center, has found a probable cause. The loss of function of two genes was found to prevent the development of motor skills. This study will help in early identification of the risk for motor development disabilities.
Motor Development Disability in Children Linked To Loss of Gene Function

The neural circuits in the motor cortex region of the brain and the spinal cord were not re-organized well during maturation when there is a loss of function of the genes.

Newly Identified Genetic Pathway for Motor Development Disabilities

As a part of the study, the research team bred mice that lacked the molecular signaling of the Bax/Bak pathway. The study findings showed that
  • The Bax/Bak pathway's downstream molecular targets were essential for the development of sophisticated connections that existed between the spinal circuits and motor cortex.
  • Mutations identified in the Bax/Bak pathways can be used as markers of developmental motor disabilities in humans.
Further studies are required to determine if
  • These disruptions in the Bax/Bak pathways are present among people with skilled motor disabilities.
  • The Bax/Bak pathway is involved in the regulation of re-organization of other aspects of the central nervous system of mammals.

Development of Motor Skills

Previous studies have found that only basic unskilled motor tasks may be carried out by young postnatal mammals, which includes human babies. This is because infantile neural circuitry is activated antagonistically, with muscles opposed to each other being activated at the same time.
  • The neural circuits between the spinal cord and the brain, re-organize as mammals and humans begin to grow above infancy
  • The neural connections begin to get more sophisticated
  • Antagonistic pairs of muscles are activated reciprocally

Developmental Motor Disabilities

Children who suffer from developmental motor disabilities have limited skilled motor abilities. A large proportion of these people have an immature method of co-activating muscle pairs into adulthood. This affects their dexterity.

Dyspraxia

During the process of a child's development, there could be an impairment or immaturity that occurs in the organization of movement. There is an immaturity during the processing of information in the brain. A child diagnosed with dyspraxia is found to have problems with the way language is perceived.
  • Dyspraxia is an inherited condition, in many instances, and it runs in the family.
  • Males are more likely to be affected than females.
  • This condition is also known as perceptuo motor dysfunction, clumsy child syndrome and motor learning difficulties.
  • Some of the characteristic features of this condition include an appearance of being out of sync, vision problems, writing, posture problem, difficulty with speaking, reading and writing and poor memory. The intelligence of people with this disorder is above average or average but their limb movements are immature.

Identifying Brain Connections in Developing Mice

The genetic pathways that are involved in the circuitry between corticospinal neurons in the motor cortex and muscles of the mice brain were identified using trans-synaptic viral and electrophysiological assays. This was used to identify connections that developed in maturing mice.

The trans-synaptic tracing that was used in the current study showed
  • The importance of Bax/Bak signaling in the circuity of the brain of mice that matured.
  • That the development of circuits was also triggered by the Bax/Bak signaling.
  • That the opposing muscle groups were found to be activated reciprocally.
  • That the circuitry that developed in the absence of Bax/Bak signaling restricted reciprocal activation of these muscles.

Tests to Assess Motor Skills

The mice that were deficient in the Bax/Bak pathway were subjected to skilled motor tests and it was found that the animals had
  • Unusual co-activation of opposing flexor muscle pairs and extensor
  • Normal reaching as well as retrieval behaviors when they were given food
  • Insufficiency in grasping skills
  • Difficulty with tests associated with walking on a metal grid and a balance bar, when measured by foot slips

Disability Among Indians

It is important for optimum development of children during their early years to ensure healthy transition to adulthood. Nearly 200 million children across the world do not reach their developmental potential during the first five years of their life due to poor health, nutrition, lack of awareness or due to disorders.

According to the World Health Organization
  • Globally, 15-20% of children have disabilities
  • 85% of children with disabilities live in developing countries
  • According to data from the Census of India (2011)
  • 7,862,921 children live with disability in India
  • 1,045,656 are affected with movement disorder
Research into causes of development disorders is necessary to develop preventive strategies or effective therapy for children with developmental disability. The current study identified the significance of the Bax/Bak pathway in the development of motor disabilities; further studies conducted on humans will help in providing better insights into the complex process of maturation to adulthood.

References:
  1. What is Dyspraxia? - (http://www.dyslexiaindia.org.in/Dyspraxia.html)

Source: Medindia

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