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1p36 deletion syndrome is considered one of the most common chromosome deletion syndromes; in the USA, the birth prevalence is estimated at 1/ 5,000. A higher frequency is observed among females.

Patients share recognizable craniofacial dysmorphism with microbrachycephaly, a large, late-closing anterior fontanel (>3 cm at birth), straight eyebrows, deep-set eyes, broad and depressed nasal bridge, midface retrusion, posteriorly rotated, low-set, abnormal ears, long philtrum, and pointed chin. Brachydactyly, camptodactyly and short feet are also characteristic. Almost all patients suffer from congenital hypotonia, contributing to feeding difficulties, delay in motor development and fine motor skills, and delayed or absent speech. A variable level of intellectual disability is observed in all patients. Other symptoms include prenatal-onset growth deficiency, structural brain abnormalities, seizures, congenital heart defects, eye/vision problems, hearing loss (sensorineural or conductive/glue ear), skeletal anomalies, abnormalities of the external genitalia and, less frequently, renal abnormalities and hypothyroidism.

1p36 deletion syndrome is caused by a partial heterozygous deletion that primarily involves the distal part of the short arm of chromosome 1, with breakpoints ranging from 1p36.13 to 1p36.33. About 50% of cases are due to a de novo terminal 1p36 deletion, around 29% to an interstitial deletion; remaining cases comprise more complex chromosome rearrangements.

Diagnosis is based on the clinical picture and is confirmed by chromosomal analysis. Molecular techniques are used for the genetic characterization of the deletion (fluorescence in situ hybridization, comparative genomic hybridization array). An evaluation for congenital heart defects with an echocardiogram and electrocardiagram; brain abnormalities with magnetic resonance imaging; seizures with an electroencephalogram; a neurodevelopmental assessment, and standard examinations for eye/vision problems, hearing loss, and skeletal and renal abnormalities are recommended.

Differential diagnosis includes Rett syndrome, Angelman syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, Cohen syndrome, and Aicardi syndrome.

Antenatal testing is feasible when a 1p36 chromosome rearrangement is already identified in a family member.

Most cases are sporadic, but an unbalanced translocation may be inherited from a parent with a balanced rearrangement.

Management should be multi-disciplinary and include a regular follow-up. Early diagnosis and access to personalized rehabilitation therapies focusing on motor development, cognition, communication, and social skills are highly recommended. The use of sign language is helpful. Some congenital heart defects may resolve on their own, others may require medication or surgery. Epileptic seizures are treated with standard antiepileptics. Infantile spasms are responsive to corticotrophin. Feeding and growth should be monitored as feeding difficulties are common early on. Triiodothyronine, thyroxine, and thyrotropin levels should be evaluated at diagnosis, and, then, once a year.

The severity of the 1p36 deletion syndrome varies between affected individuals. Seizures and other medical issues seem to improve with time. Patients will remain dependent on others for most activities of daily living and will require medical support throughout life. Individuals with 1p36 deletion syndrome survive well into adult life.