Introduction

CHARGE syndrome is a rare genetic condition and the letters stand for:

• Coboloma (incompleteness of the iris in the eye)
• Heart disease
• Atresia of the choana (blocked nasal passages)
• Restriction of growth and mental development
• Genital anomalies
• Ear malformations and hearing loss 

This syndrome is caused by a mutation in the DNA-binding protein-7 CHD7 gene.^1,2

Definition and diagnostic criteria

The diagnosis of CHARGE syndrome (CS) is based on 4 major or 3 minor characteristics, and it does not depend on a genetic test.^1,4 The major criterias are:

• Coloboma
• Cranial nerve abnormalities
• Choanal atresia
• Typical CHARGE ear

The minor criterias are:

• Heart defects
• Cleft lip or palate
• Genital abnormalities
• Hypotonia (decreased muscle tone)
• Kidney abnormalities
• Oesophageal atresia (blocked oesophagus)
• Poor growth
• Typical CHARGE face
• Typical CHARGE hand¹

Importance of behavioural phenotyping

CHARGE syndrome behavioural phenotypes provide an alternative for psychiatric diagnosis.⁵  There are seven of them, which are:

• Low-normal cognitive functioning
• Very goal-directed and persistent with a sense of humour
• Socially interested but immature
• Repetitive behaviours increase under stress
• High degree of sensation seeking
• Under conditions of stress and sensory overload, individuals find it difficult to self-regulate and easily lose behavioural control
• Difficulty with shifting attention and moving on to new things; easily lost in one’s thoughts

Relevance for early intervention and support planning

People born with CHARGE syndrome are most vulnerable in their early life and can have complications such as swallowing difficulties, aspiration, corneal ulceration, and retinal detachment.¹ It’s not uncommon for a child with CHARGE syndrome to be followed by various medical specialists and have undergone surgeries before the age of 10.

Neurodevelopmental profile of charge syndrome

Cognitive functioning

Frequently, specific behavioural problems can be associated with genetic syndromes. Patients with CHARGE syndrome are often diagnosed with psychiatric conditions, such as obsessive-compulsive disorder, attention deficit disorder, tourette syndrome, and autism. However, the diagnosis of autism remains a challenge in individuals with sensory impairments. Whether the symptomatology is autism or the consequence of sensory deprivation remains unknown.

Range of intellectual abilities

Children with CHARGE syndrome can have multiple sensory impairments, including vision, hearing, and balance. Therefore, it’s essential to seek a comprehensive education programme that meets their needs. A study showed that although psycho-motor milestones from 0 to 4 years were severely delayed, intellectual outcome at primary-school age was satisfactory for half of the children in this series.²

Autism spectrum features in charge syndrome

Prevalence and overlap

According to a study, the prevalence of autism spectrum disorder (ASD) in individuals with CHARGE syndrome varies from 9% to 68% due to differences in ASD definition.² Although, some behaviours common in CHARGE syndrome are similar to autistic traits, those affected by the former usually have better communication skills and more interest in social relationships when compared with people with autism. The use of formal tests to screen for autism spectrum, obsessive-compulsive disorders, and ADHD is recommended.⁶ 

Communication deficits

According to a study, verbal individuals affected by CHARGE syndrome were similar to children with autism. Nonverbal participants with CS had significantly fewer communication difficulties than nonverbal children with autism.⁴

Restricted/repetitive behaviours

According to a study, people with CS showed less repetitive behaviour compared to children with autism.⁴

ADHD features in charge syndrome

Hyperactivity/impulsivity

According to a study, 72% of participants exhibited more specific characteristics associated with emotions, 65% showed sensory hyporeactivity, and 51.3% were more active and restless than normal.⁴

Neurobiological and developmental considerations

Role of the CHD7 gene in attention regulation

The chromodomain helicase DNA-binding (CHD) family have been related to neurodevelopmental disorders. According to a study, an incomplete or underdeveloped cerebellum appears to be a major morphological abnormality in CHARGE syndrome. CHD7 plays a role in regulating genes involved in cerebellar morphogenesis during early fetal cerebellar development, possibly explaining the overlap in presentations.⁷

Peer interaction and emotional regulation

Anxiety

People affected by CHARGE syndrome often experience circumstances that contribute to a higher level of anxiety, such as concern over pain, sensory overload or underload, and lack of predictability in the environment.⁵

Emotional regulation

Emotional regulation strategies should be taught to people with CHARGE syndrome, as this could help their physiological development and their interaction with the environment.⁵

FAQs

Is autism common in CHARGE syndrome?

Autism spectrum disorder (ASD) is diagnosed in 9%-68% of individuals with CHARGE, depending on the criteria used. While some behaviours mimic autism, individuals with CHARGE often have better communication skills and more social interest than those with autism.

How can professionals distinguish between autism and CHARGE-related behaviours?

Distinction is challenging due to overlapping features and sensory impairments. Formal diagnostic tools are essential, and evaluations must consider the unique sensory and medical context of the individual.

What causes attention difficulties in CHARGE syndrome?

The CHD7 gene, which is affected in CHARGE, is involved in early brain development. Disruption in this gene can impact cerebellar growth and functions related to attention and regulation.

What interventions can help with behavioural and emotional regulation?

Effective interventions include:

• Teaching self-regulation strategies
• Sensory integration therapy
• Social skills training
• Multidisciplinary support (including educators, psychologists, and therapists)