Symptoms And Characteristics Of Fragile X Syndrome In Boys

Brief overview of Fragile X Syndrome (FXS) 

Fragile X Syndrome (FXS) is a genetic disorder characterized by intellectual disability (ID) and various physical and behavioural features. It was first described in 1943 by Martin and Bell and later associated with an X-linked inheritance pattern.¹ The prevalence of FXS is estimated to range between 1 in 5000-7000 men and 1 in 4000-6000 women worldwide.²

Affected individuals typically present ID, a characteristic long face, large and protruding ears, and increased testicular volume in males. Females with only one copy of the fully mutated version of Fragile X Mental Retardation-1 gene (FMR1) may exhibit a wide range of intellectual abilities, with some not showing any effects and others experiencing learning deficits and emotional difficulties.³

Genetic profile and diagnosis in males

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is determined by how genes are inherited on the X chromosome and is considered the most common inherited cause of ID and the most prevalent cause of ID in males.¹ On top of this, the classic phenotype is also characterized by a long face, large and protruding ears, and macroorchidism (increased testicular volume).

The diagnosis of FXS is based on the detection of an alteration in the FMR1 gene, typically involving an increased number of DNA building blocks, resulting in a loss or heavy reduction of the protein product (FMRP).³ This absence of FMRP leads to the characteristic features observed in affected individuals. 

Additionally, boys with FXS may commonly be co-diagnosed with Autism Spectrum Disorder (ASD), attention and learning problems, anxiety, aggressive behaviour, and sleep disorders.⁴

Importance of early detection and intervention

Early detection and intervention play a crucial role in FXS for several reasons. Firstly, FXS is a neurodevelopmental disorder that can significantly impact a child's cognitive, behavioural, and emotional development. Early identification allows for prompt initiation of interventions tailored to the individual's needs, which can lessen the impact of the syndrome on their overall development.

Secondly, early intervention can help address specific challenges associated with FXS, such as ID, ASD, attention and learning problems, anxiety, aggressive behaviour, and sleep disorders.⁴ By using appropriate therapies and strategies early on, individuals with FXS can receive support to maximize their potential and improve their quality of life.

Thirdly, early detection makes it easier for individuals to access specialised services and resources, including educational support, behavioural therapy, and medical management. These interventions can help address the diverse needs of individuals with FXS and empower families and caregivers to better support their loved ones.

Symptoms of fragile X syndrome in boys 

Physical characteristics 

1. Facial features

• Broad forehead
• Elongated face
• Large prominent ears
• Strabismus is a misalignment of the eyes, leading to reduced eye coordination
• Simple helix and simple antihelix contribute to unique ear shape
• Prominent jaw⁵

2. Body structure

• Hand calluses: While not universal, hand calluses from hand biting may be observed in some individuals with FXS, particularly as a response to sensory stimuli or behaviours
• Pectus excavatum: condition characterized by a sunken or depressed sternum, affecting the chest wall's shape
• Flat feet: where the arch of the foot is flattened
• Macroorchidism: This condition refers to enlarged testicles, which may become more apparent as boys reach around eight years of age
• Dermatoglyphic abnormalities: Abnormal patterns of skin ridges on the hands and feet
• Hyperextensible joints: where joints can move beyond the normal range of motion, particularly noticeable in the joints of the hand that connect the palm to the fingers⁵

B. Developmental delays 

1. Speech and language delays 

• Verbal perseveration: repeat words or phrases excessively
• Abnormal language development: Speech and language delays are common, with individuals showing difficulties in expressive and receptive language skills
• Fast speech: Some may speak rapidly, making it challenging for others to understand them clearly.
• Poor eye contact: which can affect social communication and language development
• Tactile defensiveness: making it challenging for individuals to engage in activities involving touch, potentially hindering speech and language therapy

2. Motor skill delays 

• Locomotor hyperactivity: which can impact their motor coordination and control
• Sensory hyperactivity: may affect motor skill development, as individuals may avoid certain activities or environments
• Unusual physical marks: an elongated face, flat feet, and extended finger joints may also be associated with motor skill delays, affecting fine and gross motor abilities
• Delayed milestones: such as sitting, crawling, and walking
• Fine motor challenges: such as grasping objects or manipulating small items, are common and may impact activities of daily living and academic performance

C. Behavioural and emotional symptoms

1. Social anxiety 

• Social shyness: leading to avoidance of social interactions
• Gaze aversion: which may indicate discomfort or anxiety in social situations
• Difficulty relating to people: especially in unfamiliar or new situations
• Heightened anxiety: Social situations, task demands, and changes in routine may result in heightened anxiety due to hyperarousal of the autonomic system

2. Hyperactivity 

• Locomotor hyperactivity: characterised by excessive physical movement and restlessness
• Increased activity level: making it challenging to engage in focused tasks or activities
• Resistance to changes in routine: Hyperactivity may also manifest as resistance to changes in routine, with individuals displaying agitation or distress when faced with transitions

3. Repetitive behaviours 

• Perseverative speech and language: where they may repeat words or phrases excessively
• Stereotypies: Hand flapping, hand movements, or other repetitive behaviours are often observed, reflecting a need for sensory stimulation or self-soothing
• Object use and communication: such as repeating specific actions or phrases

4. Sensory sensitivities

• Tactile defensiveness: may lead to discomfort or avoidance of certain textures or sensations
• Unusual responses to sensory stimuli: such as heightened sensitivity to noise, light, or touch
• Limited taste, smell, and touch response: may be more pronounced and specific compared to typical developmental variations^6,7

Autism spectrum disorder (ASD) traits in FXS

FXS is strongly linked to autistic characteristics, including stereotyped and repetitive behaviours, poor eye contact, and social avoidance. Approximately 20–50% of males with FXS may also meet the criteria for autism, and up to three-quarters may exhibit autistic traits.⁸

Autistic features in FXS may include difficulties in peer social play, verbal and nonverbal communication, repetitive motor behaviours, and unusual responses to sensory stimuli. Sensory dysfunction may be less prominent in FXS compared to autism. Some autistic-like behaviours in FXS may be situation-specific rather than pervasive, suggesting a difference in the underlying mechanisms between FXS and autism.⁹

Summary

Physical characteristics, along with behavioural traits like verbal perseveration, poor eye contact, and tactile defensiveness, contribute to the clinical profile of FXS. These developmental delays in speech, language, and motor skills are significant features of FXS and can vary in severity among affected individuals.

Individuals with FXS, particularly males, exhibit a range of cognitive, behavioural, and communicative challenges, with significant overlap with autism spectrum disorder in terms of traits and characteristics. Understanding these characteristics is crucial for early identification and appropriate intervention strategies, which could help improve the life of the FXS individual and those around them.