Monosomy 1p36 syndrome

Terminal deletion of the short arm of chromosome 1 (1p36). The most common terminal deletion syndrome (~1 in 5,000 births). Most are de novo; ~20% from unbalanced translocations of a parent. Deletion size and breakpoints vary, which contributes to phenotypic variability.

• Severe intellectual disability with limited speech
• Hypotonia and feeding difficulties in infancy
• Microcephaly with characteristic facies: straight eyebrows, deep-set eyes, midface retrusion, pointed chin, low-set/posteriorly rotated ears
• Seizures (~50%, often refractory) and cortical visual impairment
• Cardiomyopathy: left ventricular non-compaction (LVNC) is over-represented and a major cause of mortality
• Structural CHD (~70%): PDA, ASD, VSD, valve anomalies
• Behavior: self-injury, autistic features common
• Hearing loss; ophthalmologic findings (strabismus, refractive errors)

• Chromosomal microarray (CMA) is the test of choice: detects the deletion and characterizes its size
• Karyotype may miss small deletions; FISH for 1p36 confirms when CMA isn't available
• Parental karyotype/FISH if a translocation is suggested by clinical context (recurrence implications)

• Other terminal deletion syndromes (Wolf-Hirschhorn 4p-, Cri-du-chat 5p-): different facies, different phenotype
• Angelman syndrome: seizures + ID + hypotonia, but happy demeanor and characteristic EEG; methylation analysis
• Rett syndrome: regression, hand stereotypies, female predominance; MECP2

• Cardiology: baseline echo + serial echocardiography (LVNC surveillance is life-saving)
• Neurology: seizure management
• Developmental: early intervention, augmentative communication
• GI: feeding evaluation, possible G-tube
• Family genetic counseling: most de novo, low recurrence; if parental translocation, ~25-50% recurrence