22q13 deletion syndrome, also known as Phelan-McDermid syndrome (PMS), is a rare genetic condition. It arises from the loss of a small segment of genetic material from chromosome 22. This syndrome is characterized by a range of developmental, intellectual, and physical features that can vary in severity among individuals.
Understanding the Genetic Cause
22q13 deletion syndrome results from a missing piece of genetic information on the long arm (q) of chromosome 22, specifically at band q13.3. This deletion varies in size, from very small to much larger. The size of the missing segment can influence the specific characteristics an individual experiences.
The SHANK3 gene, located within this deleted region, is a primary contributor to many of the syndrome’s features. The SHANK3 gene provides instructions for making the SHANK3 protein, important for brain development and function. This protein plays a role in the synapses, which are the connections between nerve cells, and a reduction in its amount can impair nerve cell signaling.
Recognizing the Characteristics
Individuals with 22q13 deletion syndrome present with characteristics affecting development, physical appearance, and behavior. Global developmental delay is a universal feature. Intellectual disability, ranging from moderate to profound, is often observed. Speech and language development are severely delayed or absent, a hallmark of the syndrome.
Low muscle tone (hypotonia) is present in most affected newborns and can persist into adulthood, impacting feeding, reflexes, and motor skills. While growth is normal or even accelerated, many individuals display subtle physical features. These can include a long, narrow head, prominent or unusually shaped ears, full cheeks, a bulbous nose, a pointed chin, and long eyelashes. Hands may appear large and fleshy, and some individuals may have abnormal toenail growth or webbing of the second and third toes.
Behavioral traits include autism spectrum disorder features, such as poor eye contact, repetitive movements, and reduced social interaction. Sensory processing differences include a decreased sensitivity to pain, and a tendency to chew on non-food items. Additional issues include seizures and gastrointestinal problems like cyclic vomiting and gastroesophageal reflux.
Diagnosis and Early Identification
Diagnosis of 22q13 deletion syndrome is confirmed through specialized genetic testing. While a standard karyotype, which examines chromosomes, can sometimes detect larger deletions, many are too small to be seen with this method. Therefore, chromosomal microarray analysis (CMA) or fluorescence in situ hybridization (FISH) are the recommended diagnostic tools. CMA can identify small genetic deletions or duplications across the genome, offering a higher resolution than traditional karyotyping. FISH uses fluorescent probes to detect specific chromosomal abnormalities, including those at 22q13.3.
Early identification is beneficial for initiating timely interventions and support services. Genetic counseling is an important part of the diagnostic process, providing families with information about the syndrome, its inheritance patterns, and the potential for recurrence in future pregnancies. Most cases of 22q13 deletion syndrome occur randomly, meaning the deletion is not inherited from the parents. However, in some instances, a parent may carry a balanced chromosomal rearrangement that increases the risk of recurrence, necessitating parental genetic testing and counseling.
Support and Management Strategies
Management of 22q13 deletion syndrome involves a multidisciplinary approach focused on addressing the diverse needs of each individual. Early intervention programs offer support from infancy through early childhood. Therapies such as speech therapy are important for developing communication skills, given the significant speech delays often seen. Occupational therapy helps individuals improve fine motor skills, daily living activities, and sensory processing. Physical therapy works to strengthen muscles, improve gross motor skills, and manage hypotonia.
Behavioral therapy, including applied behavior analysis (ABA), can assist in managing challenging behaviors and promoting adaptive skills. For school-aged children, individualized education plans (IEPs) are developed to tailor educational support to their specific learning styles and needs. Ongoing medical management is also necessary to address associated health issues such as seizures or gastrointestinal problems like cyclic vomiting or reflux. Family support groups and community resources play a significant role in providing emotional support, sharing experiences, and connecting families with valuable information and services.