Introduction

DiGeorge Syndrome (22q11.2 Deletion Syndrome)

Demographic Information:

• Incidence: DiGeorge syndrome occurs in approximately 1 in 3,000 to 6,000 live births.
• Prevalence: The global prevalence of DiGeorge syndrome is estimated to be around 1 in 4,000 individuals, with some variations depending on the population studied.
• Gender: DiGeorge syndrome affects males and females equally.
• Onset Age: Symptoms of DiGeorge syndrome can be present from birth, but the full spectrum of features often becomes more apparent in early childhood.

Coding:

• ICD-11: LD43
• OMIM: 192430
• UMLS: C0265285
• MeSH: D020167
• GARD: 1411

Medical Features and Pathophysiology

• Etiology: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is caused by a microdeletion of a small segment of chromosome 22 at the q11.2 location. This deletion affects approximately 30-40 genes that are crucial for the development of various organ systems, including the heart, thymus, parathyroid glands, and palate. The deletion is typically de novo, occurring randomly during the formation of reproductive cells or early fetal development, but it can also be inherited in an autosomal dominant manner.
• Pathology: The deletion at 22q11.2 disrupts the development of the third and fourth pharyngeal pouches during fetal development. These pouches are critical for the formation of several structures:

- Parathyroid Glands: Regulate calcium levels in the body. Underdevelopment of the parathyroid glands results in hypocalcemia (low calcium levels), which can cause seizures, muscle spasms, and other neurological problems. - Heart: The deletion can affect the development of the heart, leading to congenital heart defects. Common heart defects include tetralogy of Fallot, ventricular septal defects, and truncus arteriosus. - Palate: The deletion can also affect the development of the palate, resulting in cleft palate or velopharyngeal insufficiency (VPI). These palatal abnormalities can cause feeding difficulties, speech problems, and recurrent ear infections.

• Symptoms:

- Immunodeficiency: Due to thymic hypoplasia or aplasia, individuals with DiGeorge syndrome have a weakened immune system, making them more susceptible to infections, particularly respiratory and ear infections. The severity of immunodeficiency varies, with some individuals experiencing frequent and severe infections, while others have milder immune problems. - Hypocalcemia: Low calcium levels are common in DiGeorge syndrome due to parathyroid gland dysfunction. Hypocalcemia can cause seizures, muscle spasms (tetany), and other neurological symptoms. - Palatal Defects: Cleft palate or submucosal cleft palate can lead to feeding difficulties, speech problems, and recurrent ear infections. These palatal abnormalities may require surgical repair and speech therapy. - Facial Features: Characteristic facial features may include hooded eyelids, a prominent nasal bridge, small ears, a small mouth, and a long face. However, facial features can vary widely among individuals with DiGeorge syndrome. - Developmental Delays: Children with DiGeorge syndrome often have delays in speech and motor development. Learning disabilities are common, and intellectual disability can range from mild to moderate. - Behavioral and Psychiatric Disorders: Individuals with DiGeorge syndrome have an increased risk for behavioral problems, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, and psychiatric conditions such as anxiety, depression, and schizophrenia.

• Diagnosis: Diagnosis of DiGeorge syndrome is based on a combination of clinical findings and genetic testing.

- Genetic Testing: Genetic testing is necessary to confirm the diagnosis. Fluorescence in situ hybridization (FISH) is the most common method used to detect the 22q11.2 deletion. Other genetic testing methods, such as chromosomal microarray analysis (CMA) or multiplex ligation-dependent probe amplification (MLPA), can also be used.

Assistive Technology Suggestions and Requirements

Requirement Percentage for Assistive Technology

A significant percentage of individuals with DiGeorge syndrome, estimated between 80-90%, will require some form of assistive technology to support their communication, learning, and daily living activities. The specific needs for assistive technology will vary depending on the individual's strengths and challenges.

Assistive Technology Suggestions

• Communication Devices: Augmentative and alternative communication (AAC) devices are essential for individuals with DiGeorge syndrome who have significant speech and language impairments. These devices can range from low-tech options, such as picture exchange systems and communication boards, to high-tech options, such as speech-generating devices and tablet-based communication apps. The selection of an AAC system should be based on the individual's cognitive abilities, motor skills, and communication needs.
• Educational Tools: Adaptive learning tools, such as specialized software, apps, and assistive technology devices, can support academic achievement and learning. Visual aids, interactive technology, and text-to-speech software can be particularly beneficial for individuals with learning disabilities.
• Mobility Aids: Depending on the severity of motor skill delays or physical disabilities, some individuals with DiGeorge syndrome may benefit from mobility aids, such as walkers, crutches, or wheelchairs. These aids can enhance independence and participation in activities.
• Adaptive Equipment for Daily Living: Adaptive equipment, such as specialized utensils, dressing aids, and bathroom aids, can help individuals with DiGeorge syndrome perform daily living tasks more independently.

Access Modalities

• Direct Selection: Individuals with sufficient motor control may be able to directly select symbols or items on a communication device or computer using their finger, hand, or a pointer. Adapting interfaces with larger icons, simplified layouts, and adjustable touch sensitivity can enhance accessibility.
• Switch Access: For individuals with limited motor control, switch access enables interaction with assistive technology using various body parts, such as a head switch, hand switch, or foot switch. The type of switch and its placement should be individualized based on the individual's abilities and preferences.
• Eye-Gaze Technology: Eye gaze systems allow individuals to control devices using their eye movements. This technology is particularly beneficial for those with severe motor impairments who cannot use their hands effectively. Eye gaze systems require good ocular control and the ability to fixate gaze, which may require specialized training and adaptations.

Care Management and Therapeutic Techniques

Aims

The primary aims of care management for individuals with DiGeorge syndrome are:

• Address Cardiac and Immunological Issues: Managing congenital heart defects and immunodeficiency is crucial to ensure the individual's health and well-being. This involves regular monitoring by cardiologists and immunologists, surgical interventions as needed, and preventive measures to reduce the risk of infections.
• Support Cognitive and Social Development: Early intervention and ongoing therapies are essential to maximize developmental potential and address cognitive and social challenges. This includes providing therapies that target speech and language development, motor skills, cognitive abilities, and social-emotional skills.
• Manage Behavioral Problems: Behavioral problems, such as ADHD, autism spectrum disorder, and other behavioral challenges, can significantly impact the individual's quality of life. Behavioral therapy, medication management, and environmental modifications can be helpful in addressing these challenges.
• Improve Overall Quality of Life: The ultimate goal of care management is to improve the individual's overall quality of life by addressing their specific needs and challenges, promoting independence, and fostering social inclusion.

SLP (Speech-Language Pathologist) Suggestions

• Comprehensive Speech and Language Assessment: Conduct a thorough evaluation of the individual's receptive and expressive language abilities, oral-motor skills, articulation, phonological awareness, and overall communication needs. This assessment should include standardized tests, parent/caregiver interviews, and naturalistic observations.
• Early Intervention: Initiate speech and language therapy as early as possible to maximize communication potential. Focus on developing pre-linguistic skills, such as joint attention, turn-taking, and symbolic play, which lay the foundation for later language development.
• Articulation and Phonological Therapy: Address articulation errors and phonological processes that may be present due to structural abnormalities, such as cleft palate or VPI. Implement targeted exercises and techniques to improve speech clarity and intelligibility.
• Language Stimulation Techniques: Use evidence-based language stimulation techniques, such as expansions, extensions, and recasts, to promote language growth. Create language-rich environments that encourage communication and provide ample opportunities for the individual to express themselves.
• AAC System Selection and Implementation: Work closely with the individual, family, and other professionals to select the most appropriate AAC system based on the individual's abilities, needs, and preferences. Provide ongoing training and support to ensure successful implementation and generalization of AAC use across settings.
• Oral-Motor and Feeding Therapy: Address any oral-motor deficits that may impact speech production, feeding, and swallowing. Implement exercises and strategies to improve muscle strength, coordination, and range of motion in the oral-facial region. Collaborate with occupational therapists and other professionals to manage feeding difficulties and ensure safe swallowing.
• Social Communication Interventions: Target social communication skills, such as initiating and maintaining interactions, responding to others, understanding social cues, and engaging in turn-taking. Use social stories, role-play, and video modeling to teach social norms and expectations.
• Literacy Development: Support emergent literacy skills by incorporating shared book reading, print awareness activities, and phonological awareness tasks into therapy sessions. Adapt literacy materials to accommodate the individual's visual and motor impairments.
• Collaboration and Consultation: Work closely with families, educators, and other professionals to ensure consistent implementation of communication strategies across environments. Provide training and support to caregivers to promote effective communication at home and in the community.

Special Educator Suggestions

• Individualized Education Plan (IEP): Develop and regularly update an IEP that includes specific goals and accommodations tailored to the student's strengths and needs. The IEP should address academic, social-emotional, communication, and functional skills development.
• Inclusive Education: Promote inclusion in mainstream classrooms with appropriate supports and accommodations. This may involve providing assistive technology, visual aids, preferential seating, and individualized instruction.
• Behavioral Interventions: Implement behavior management strategies to address challenging behaviors, such as hyperactivity, impulsivity, and emotional outbursts. Positive reinforcement, clear expectations, structured routines, and sensory breaks can be effective.
• Functional Skills Training: Emphasize the development of life skills, such as self-care, vocational training, and adaptive skills, to promote independence and self-sufficiency.

Occupational Therapist Suggestions

• Comprehensive Occupational Therapy Assessment: Conduct a thorough evaluation of the individual's fine motor skills, visual-motor coordination, sensory processing, and adaptive behavior. Use standardized assessments, clinical observations, and parent/caregiver interviews to gather information.
• Fine Motor Skill Development: Implement activities and exercises to improve hand strength, dexterity, and manipulation skills. Use adaptive tools and techniques to accommodate motor impairments and maximize independence in daily tasks.
• Visual-Motor Integration: Address deficits in visual-motor coordination through activities that involve eye-hand coordination, visual tracking, and visual scanning. Use visual cues and tactile feedback to support accurate motor responses.
• Sensory Processing Interventions: Identify sensory processing difficulties and develop individualized sensory diets to help regulate sensory input. Incorporate sensory-based activities, such as deep pressure, weighted vests, and tactile stimulation, into daily routines to promote optimal arousal and engagement.
• Adaptive Equipment and Environmental Modifications: Recommend and train the individual and caregivers in the use of adaptive equipment, such as special seating systems, mobility devices, and feeding aids. Modify the environment to enhance accessibility, safety, and independence.
• Activities of Daily Living (ADLs): Teach strategies and techniques to improve independence in self-care tasks, such as dressing, grooming, and toileting. Break down complex tasks into smaller steps and use visual supports to facilitate learning.
• Play and Leisure Skills: Promote engagement in age-appropriate play and leisure activities to support cognitive, social, and emotional development. Adapt toys and games to accommodate motor and sensory impairments.
• Collaboration with Other Professionals: Work closely with physical therapists, speech-language pathologists, and educators to ensure a comprehensive and coordinated approach to intervention. Share information and strategies to support the individual's participation and progress across settings.

Recommendations for AAC

• Early Introduction: Introduce AAC as early as possible, even if the individual has some spoken language. AAC can support language development, reduce frustration, and provide a consistent means of communication.
• Multimodal Approach: Encourage a multimodal communication approach that incorporates gestures, sign language, vocalizations, and AAC devices. This allows the individual to communicate in various ways depending on the situation and their abilities.
• Personalized Vocabulary: Customize AAC systems with vocabulary that is meaningful and relevant to the individual's daily life, interests, and communication needs. Regularly update vocabulary as the individual's language skills and interests evolve.
• Consistent Use: Encourage consistent use of AAC across environments, including home, school, and the community. Train communication partners, such as family members, educators, and therapists, on how to use and support the AAC system effectively.

Challenges and Considerations

• Medical Complexity: Managing the multiple medical issues associated with DiGeorge syndrome, including heart defects, immunodeficiency, hypocalcemia, and other medical complications, requires a coordinated approach involving various healthcare professionals. Families may need support in navigating the healthcare system and advocating for their child's needs.
• Developmental Delays and Learning Disabilities: The developmental delays and learning disabilities associated with DiGeorge syndrome can pose significant challenges for individuals and their families. Access to early intervention programs, specialized education services, and ongoing therapies is crucial to maximize developmental potential and support learning.
• Behavioral and Psychiatric Issues: The increased risk for behavioral problems, ADHD, autism spectrum disorder, and psychiatric conditions can significantly impact the individual's quality of life and require specialized interventions and support.
• Social Integration: Individuals with DiGeorge syndrome may face challenges with social integration due to communication difficulties, behavioral issues, and physical limitations. Promoting social interactions, fostering friendships, and creating inclusive environments are essential to enhance their quality of life.
• Long-Term Care: Individuals with DiGeorge syndrome may require lifelong support and supervision, particularly those with significant intellectual disability or medical complications. Planning for long-term care needs, including residential options, financial planning, and legal guardianship, is essential.

Differential Diagnosis

• Velocardiofacial Syndrome (VCFS): VCFS is essentially the same condition as DiGeorge syndrome, caused by the same 22q11.2 deletion. The terms are often used interchangeably.
• Conotruncal Anomaly Face Syndrome: This syndrome is also caused by the 22q11.2 deletion and overlaps significantly with DiGeorge syndrome.
• Other Conditions with Similar Features: Several other genetic and developmental disorders can share some features with DiGeorge syndrome, making differential diagnosis important. These conditions include:

- Noonan Syndrome: Characterized by short stature, distinctive facial features, heart defects, and developmental delays. - Williams Syndrome: Characterized by distinctive facial features, cardiovascular problems, developmental delays, and a unique personality profile.

Differential Diagnosis for SLPs

From an SLP's perspective, DiGeorge syndrome can present with speech and language characteristics that overlap with other disorders. Here are some conditions that might present similarly to an SLP:

• Cleft Palate: Cleft palate, a common feature of DiGeorge syndrome, can cause articulation errors, hypernasality, and velopharyngeal insufficiency (VPI). These speech characteristics can also be seen in individuals with isolated cleft palate or other craniofacial anomalies.
• Developmental Language Disorder (DLD): Children with DiGeorge syndrome often have developmental language delays that may resemble DLD. However, in DiGeorge syndrome, the language delays are often part of a broader pattern of developmental and medical issues.
• Autism Spectrum Disorder (ASD): Individuals with DiGeorge syndrome have an increased risk for ASD, which can present with communication and social interaction challenges. However, ASD is a separate diagnosis with its own set of diagnostic criteria.
• Intellectual Disability: The intellectual disability associated with DiGeorge syndrome can contribute to language delays and communication difficulties. However, it's important to assess the individual's cognitive abilities and tailor interventions accordingly.
• Hearing Loss: Hearing loss can occur in DiGeorge syndrome due to recurrent ear infections or other factors. It's essential to rule out hearing loss as a contributing factor to speech and language delays.

Future Directions and Research

• Gene Therapy: Research is exploring gene therapy approaches to replace or repair the deleted genes on chromosome 22. This holds promise for potentially correcting the underlying genetic defect and preventing or mitigating the symptoms of DiGeorge syndrome.
• Targeted Therapies: Scientists are investigating targeted therapies that address specific symptoms or complications of DiGeorge syndrome, such as immune dysfunction, hypocalcemia, and heart defects.
• Early Detection and Intervention: Research is focused on developing better methods for early detection and intervention. Early diagnosis and treatment can improve outcomes and reduce the severity of symptoms.
• Understanding Genotype-Phenotype Correlations: Research is ongoing to better understand the relationship between specific gene deletions and the clinical presentation of DiGeorge syndrome. This knowledge will help clinicians predict the course of the disorder and tailor interventions to individual needs.

Epidemiology and Demographics

Etiology and Pathophysiology

Clinical Features and Stages

Diagnosis

Clinical Recommendations

Care Management

Transition Planning