chromosome 22q11.2 deletion syndrome, distal

Chromosome 22q11.2 deletion syndrome, distal, is a multi-system condition caused by the loss of a small segment of genetic material on the long arm of chromosome 22. The deletion disrupts genes important for growth, heart formation, and neurodevelopment, leading to a wide range of physical and cognitive effects. Signs often appear in infancy or early childhood, but the presentation can vary greatly from one person to another. Precise prevalence figures are not yet established, and diagnoses are likely under-recognized because of the variable features.

Severity and symptoms vary widely between individuals. Many babies are born small or prematurely and continue to have short stature or poor weight gain. Distinctive facial characteristics—such as a smooth philtrum, highly arched eyebrows, deep-set or narrow up-slanting eyes, a thin upper lip, and a pointed chin—often prompt genetic evaluation. Early developmental concerns commonly include global developmental delay, particularly in speech and language, and mild intellectual disability. Parents may also notice atypical behavior or learning differences that require educational support. Heart involvement ranges from subtle structural differences detectable only on imaging to more significant defects such as truncus arteriosus. Because not all individuals experience cardiac problems, an echocardiogram at diagnosis is recommended. Less frequent but important findings include cleft palate, minor skeletal differences like clinodactyly, and underdeveloped nasal alae. Although rare, very distal deletions have been linked to an increased risk for malignant rhabdoid tumors, highlighting the need for attentive medical follow-up. Not all individuals experience all features, and the specific combination of problems can change over time.

The condition results from a microdeletion—meaning a small missing segment—within the distal portion of chromosome 22 at band q11.2. The loss removes multiple genes that collectively influence development of the heart, skeleton, and nervous system, though the precise genes responsible for each feature remain under study. Most affected individuals appear to have the deletion as a new genetic change, but detailed inheritance data are limited. Because recurrence risk can differ from family to family, genetic counseling is strongly recommended for parents and adult relatives who are planning future pregnancies.

Currently, management focuses on supportive care tailored to each person’s needs, and typically involves a multidisciplinary team that may include cardiology, developmental pediatrics, speech therapy, orthopedics, oncology, and genetics. Early intervention programs, speech and occupational therapies, and individualized educational plans help children reach their developmental potential. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. This monitoring often includes periodic echocardiograms for those with or at risk for heart defects, assessment of growth and nutrition, developmental and cognitive evaluations, and oncology-directed monitoring in individuals with very distal deletions associated with tumor risk. Families should work closely with their specialist team to determine an appropriate monitoring schedule and to update it as medical knowledge evolves.

Outcomes vary depending on the severity of heart disease, the degree of developmental challenges, and access to specialized care. Many children make steady developmental gains with early therapies and can attend mainstream or special-education classrooms. Heart defects, when present, may require medical or surgical management, and long-term cardiac health influences overall outlook. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialist centers experienced in chromosome deletion syndromes, participate in patient registries, and seek ongoing genetic counseling for guidance and support.

Clinical trials are underway exploring new approaches to diagnosis and management. Individuals interested in research opportunities can search ClinicalTrials.gov or discuss potential eligibility with their healthcare team.