2q23.1 microdeletion syndrome

2q23.1 microdeletion syndrome (also known as MBD5-associated intellectual disability or pseudo-Angelman syndrome) is a rare chromosomal disorder caused by a small deletion on the long arm of chromosome 2 at position 23.1. The critical gene within this region is MBD5 (methyl-CpG binding domain protein 5), and haploinsufficiency of this gene is considered the primary driver of the clinical phenotype. The condition predominantly affects the nervous system and is characterized by moderate to severe intellectual disability, significant speech and language impairment (often with absent or very limited speech), seizures, behavioral abnormalities, and motor delays. Key clinical features include childhood-onset epilepsy (reported in the majority of affected individuals), sleep disturbances, autistic-like behaviors, short attention span, and self-injurious behavior. Many patients exhibit subtle but recognizable facial features such as a broad forehead, prominent nasal bridge, thin upper lip, and open mouth appearance. Feeding difficulties in infancy, microcephaly or relative microcephaly, and short stature may also be present. The behavioral profile often overlaps with Angelman syndrome, Smith-Magenis syndrome, and other neurodevelopmental conditions, which can make clinical diagnosis challenging without genetic testing. Diagnosis is typically confirmed through chromosomal microarray analysis (CMA) or other molecular cytogenetic techniques that can detect submicroscopic deletions. Most cases arise de novo (as new mutations not inherited from parents), though the condition follows an autosomal dominant inheritance pattern when transmitted. There is currently no cure for 2q23.1 microdeletion syndrome. Management is supportive and symptomatic, including antiepileptic medications for seizure control, speech and language therapy, occupational therapy, behavioral interventions, and individualized educational programs. Sleep disturbances may require behavioral strategies or pharmacological management with melatonin. A multidisciplinary approach involving neurologists, developmental pediatricians, speech therapists, and behavioral specialists is recommended for optimal care.

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