From the Guidelines
Chromosome 11 deletions are associated with various genetic disorders, including Beckwith-Wiedemann Syndrome (BWS), which is characterized by overgrowth, enlarged organs, and increased cancer risk, particularly Wilms tumor and hepatoblastoma, as reported in a study published in Clinical Cancer Research in 2017 1.
Background on Chromosome 11 Deletions
Chromosome 11 deletions can range from small segments to large regions of the chromosome and can occur on either the short arm (11p) or long arm (11q). The specific region deleted and the size of the deletion determine the symptoms and disorders associated with the deletion.
- Jacobsen syndrome (11q deletion) is characterized by intellectual disability, facial abnormalities, and bleeding disorders.
- WAGR syndrome (11p13 deletion) is associated with Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability.
- Beckwith-Wiedemann syndrome (sometimes caused by 11p15 deletions) is characterized by overgrowth, enlarged organs, and increased cancer risk, particularly Wilms tumor and hepatoblastoma, with an overall incidence of tumor risk of 5-10% 1.
Diagnosis and Treatment
Diagnosis of chromosome 11 deletions typically involves chromosomal microarray analysis, karyotyping, or FISH testing. Treatment is supportive and symptom-based, often requiring a multidisciplinary approach with specialists in genetics, neurology, cardiology, and other fields depending on the affected systems.
- Early intervention services, physical therapy, and special education may benefit affected individuals.
- Genetic counseling is recommended for families, as some deletions occur spontaneously while others may be inherited.
Cancer Risk and Screening
The cancer risk associated with chromosome 11 deletions, particularly in BWS, highlights the importance of surveillance and screening.
- Wilms tumor and hepatoblastoma screening are recommended for individuals with BWS, using abdominal/renal ultrasound and alpha-fetoprotein (AFP) measurements 1.
- The frequency and type of screening may vary based on the specific genetic or epigenetic changes, with some studies suggesting tailored screening approaches based on the genetic cause of BWS 1.
From the Research
Chromosome 11 Deletions
- Chromosome 11 deletions are associated with Beckwith-Wiedemann syndrome (BWS), a clinically heterogeneous overgrowth syndrome with an increased risk for embryonal tumor development 2.
- BWS is caused by genetic or epigenetic alterations within two domains of imprinted growth regulatory genes on human chromosome 11p15 2.
- The syndrome can be further divided into three subsets of patients: those presenting with classic features, those presenting with isolated lateralized overgrowth (ILO), and those not fitting into the previous two categories, termed atypical BWS 3.
Molecular Characteristics
- Molecular studies of BWS have provided important data with respect to epigenotype/genotype-phenotype correlations, with alterations of Domain 1 associated with the highest risk for tumor development, specifically Wilms' tumor 2.
- Advances in molecular characterization have further delineated intricate (epi)genetic regulation of the imprinted gene cluster on chromosome 11p15.5 and the role of these genes in normal growth and development 4.
- The identification of cryptic or submicroscopic imbalances using molecular cytogenetic technologies has allowed for the identification of numerous new syndromes through a genotype-first approach 5.
Clinical Features
- Patients with BWS can present with a variety of clinical features, including overgrowth, macroglossia, and omphalocele 3, 2.
- The clinical expression of the BWS phenotype is influenced by the molecular changes associated with the syndrome, including the type and location of the genetic or epigenetic alteration on chromosome 11p15 4.
- The study of BWS has provided insight into the importance of imprinting, growth dysregulation, and tumorigenesis, and has implications for the diagnosis and management of the syndrome 6.