Fewer than 100 cases have been reported worldwide, making this a very rare condition. Children born both genetically male and female are affected at equal rate, and there is no known ethnic predilection.

Chromosome 3p26.3 deletion syndrome is caused by a deletion at the end of the short arm of chromosome 3, most commonly involving the CHL1 gene important for brain development (see RareShare guide on chromosomal nomenclature). Other genes can include CNTN4, also situated at 3p26.3, and ITPR1 located at 3p26.1 band. CNTN4 is involved in neural network formation and ITPR1 is an ion channel implicated in cerebellar ataxias. The deletion may be inherited from a parent (with variable penetrance) or may occur de novo (new in the affected individual). Inheritance, when present, is typically autosomal dominant, meaning a person with the deletion has a 50% chance of passing it to their offspring (see RareShare Guide on Genetic Inheritance).

Symptoms can vary but commonly include:

• Neurodevelopmental delay: Delayed milestones, particularly in speech and language development

• Intellectual disability: Ranges from mild to moderate

• Behavioral issues: May include attention deficit, hyperactivity, or autistic features

• Physical features: Microcephaly (small head size), ptosis (droopy eyelids), widely spaced eyes, and other subtle facial differences

Other possible findings: Hypotonia (low muscle tone), seizures (less common), and, rarely, congenital heart defects
The severity of symptoms often correlates with the size of the deletion and which genes are affected.

Genetic Testing: 

• chromosomal microarray analysis, fluorescence in situ hybridisation (FISH)

There is no cure for 3p26.3 deletion syndrome. Management focuses on supportive therapies and symptom management:

• Early intervention: Speech, occupational, and physical therapy

• Educational support: Special education services as needed

• Medical monitoring: Regular follow-up for neurological, developmental, and (if indicated) cardiac issues

• Genetic counseling: For affected families and at-risk relatives

The prognosis varies widely depending on the size of the deletion and the specific genes involved. Many individuals can achieve a degree of independence with appropriate support, while others may require lifelong care. Life expectancy is generally not reduced unless there are significant medical complications.

Ballif BC, et al. (2012). "Deletion of 3p26.3 in a child with developmental delay: Further evidence that CHL1 is a dosage-sensitive gene." American Journal of Medical Genetics Part A, 158A(8):1976-1980.
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Cuoco C, et al. (2011). "3p26.3 microdeletion syndrome: Description of a new case and review of the literature." European Journal of Medical Genetics, 54(2):145-149.
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Faivre L, et al. (2002). "Clinical and molecular characterization of 3p terminal deletion syndrome: Delineation of a critical region for speech delay." European Journal of Human Genetics, 10(11): 757-765.
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DECIPHER Database. "3p26.3 microdeletion syndrome."
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Genetics Home Reference (NIH/NLM). "3p deletion syndrome."
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OMIM Entry #612766. "Chromosome 3p26.3 deletion syndrome."
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