Chromosome 1p13.3 microdeletion syndrome is extremely rare, and only a small number of cases have been described in the medical literature. The exact prevalence is unknown. A recent study conducted in 2022 focuses on 4 cases of chromosome 1p13.3 deletion syndrome and its differences in presentation and symptomology between each individual. Increased use of high-resolution genetic testing, such as chromosomal microarray analysis, has led to the identification of additional cases in recent years.

The disorder is caused by a microdeletion involving the 1p13.3 region of chromosome 1, resulting in the loss of several genes that are important for neurological development and cellular function. In many cases, the deletion occurs de novo, meaning it arises spontaneously during the formation of reproductive cells or early embryonic development. Less commonly, it may be inherited from a parent carrying a chromosomal rearrangement such as a balanced translocation (see Rareshare Guide on Genetic Inheritance). The specific clinical features depend on the genes affected within the deleted segment.

A recent study conducted on 4 individuals with chromosome 1p13.3 deletion syndrome identified a few candidate genes. These were identified as partially or fully deleted due to CNV mapping, and are generally expressed in the fetal developing brain and the adult brain. These genes include VAV3, GSTM5, LRIF1, WDR47 and ELAPOR1.

• VAV3 - cerebellum development and axon wiring processes

• GSTM5 - antioxidant defense mechanisms

• LRIF1 - mutations have been linked to speech/motor delay, and facial dysmorphism

• WDR47 - neural stem cell proliferation, radial migration, and growth cone dynamics

• ELAPOR1 - mutations have been associated with development of other neurological development disorders (NDDs)

Symptoms vary widely among individuals but often include features related to neurological and developmental function. Reported manifestations may include:

• Developmental delay, particularly in speech and motor skills

• Intellectual disability, ranging from mild to moderate in many cases

• Hypotonia (low muscle tone) in infancy

• Behavioral or learning difficulties

• Distinctive facial features, which may include a broad forehead, widely spaced eyes, or a small chin

• Growth abnormalities, such as short stature or feeding difficulties

• Congenital anomalies, occasionally affecting the heart, skeletal system, or other organs

The severity and combination of symptoms can differ significantly depending on the size of the deletion and the genes involved.

Diagnosis is usually suspected in children who present with unexplained developmental delays or congenital anomalies. Because the clinical features are not specific to this condition, genetic testing is required to confirm the presence of the microdeletion.

• Chromosomal microarray analysis (CMA): The most sensitive and commonly used test to detect microdeletions such as 1p13.3

• Fluorescence in situ hybridization (FISH): May be used to confirm the deletion or test family members

• Karyotype analysis: May identify larger chromosomal abnormalities but may not detect very small deletions

• Parental genetic testing: Determines whether the deletion occurred de novo or was inherited
  Additional clinical evaluations, such as developmental assessments, echocardiography, or imaging studies, may be performed to identify associated medical conditions.

There is no cure for chromosome 1p13.3 microdeletion syndrome, and treatment focuses on managing symptoms and supporting development. A multidisciplinary approach may include:

• Early intervention programs, including physical therapy, occupational therapy, and speech therapy

• Special education services to support learning and developmental needs

• Medical management of associated conditions, such as heart defects or feeding difficulties

• Behavioral or psychological support for developmental or behavioral challenges
  Regular follow-up with pediatric specialists and genetic counselors is often recommended.

The prognosis varies depending on the severity of developmental delays and associated medical conditions. Many individuals with chromosome 1p13.3 microdeletion syndrome experience ongoing developmental and learning challenges, but early therapeutic intervention can significantly improve functional abilities and quality of life. Life expectancy is generally determined by the presence and severity of associated congenital anomalies, particularly cardiac or neurological complications. Because the condition is rare, long-term outcome data remain limited.

1. NIH Publication 2022

2. Unique - 1p interstitial deletions 

3. Single allele and 1p13.3 deletion syndrome