1q44 microdeletion syndrome

1q44 microdeletion syndrome (also known as monosomy 1q44 or chromosome 1q44 deletion syndrome; Orphanet code 238769) is a rare chromosomal disorder caused by a submicroscopic deletion on the long arm of chromosome 1 at band q44. This deletion typically involves the loss of several genes, including HNRNPU, FAM36A, and SMYD3, among others. The syndrome primarily affects the nervous system and is characterized by intellectual disability of variable severity, seizures (often presenting as infantile-onset epilepsy), and significant speech and language delay. Microcephaly (abnormally small head size) is a hallmark feature and reflects underlying abnormalities in brain development. Corpus callosum abnormalities, including agenesis or hypoplasia, are frequently observed on brain imaging. Additional clinical features may include facial dysmorphisms such as a round face, flat nasal bridge, widely spaced eyes (hypertelorism), thin upper lip, and low-set ears. Growth delay and short stature may also be present. Some individuals exhibit hypotonia (low muscle tone) in infancy, which can affect feeding and motor development. Behavioral difficulties, including features of autism spectrum disorder, have been reported in some patients. The size of the deletion can vary between individuals, which contributes to the variability in clinical presentation. The HNRNPU gene has been identified as a critical gene within this region, particularly associated with seizures and intellectual disability. Most cases arise as de novo (new) deletions, meaning they are not inherited from a parent. Diagnosis is typically made through chromosomal microarray analysis (array CGH). There is no cure for 1q44 microdeletion syndrome; management is supportive and symptomatic, including antiepileptic medications for seizure control, speech therapy, physical therapy, occupational therapy, and early intervention programs to optimize developmental outcomes.

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