1p36 Deletion Syndrome – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

Excerpt

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: 1p36 deletion syndrome is characterized by typical craniofacial features consisting of straight eyebrows, deeply set eyes, midface retrusion, wide and depressed nasal bridge, long philtrum, pointed chin, large, late-closing anterior fontanel (77%), microbrachycephaly (65%), epicanthal folds (50%), and posteriorly rotated, low-set, abnormal ears. Other characteristic findings include brachy/camptodactyly and short feet. Developmental delay/intellectual disability of variable degree are present in all, and hypotonia in 95%. Seizures occur in 44%-58% of affected individuals. Other findings include structural brain abnormalities (88%), congenital heart defects (71%), eye/vision problems (52%), hearing loss (47%), skeletal anomalies (41%), abnormalities of the external genitalia (25%), and renal abnormalities (22%).

Diagnosis/testing: The diagnosis of 1p36 deletion syndrome is suggested by clinical findings and confirmed by detection of a deletion of the most distal band of the short arm of chromosome 1 (1p36). Conventional G-banded cytogenetic analysis, FISH, or chromosomal microarray (CMA) can all be used to detect deletions; however, the complexity of some deletions may be detected only by CMA.

Management: Treatment of manifestations: Rehabilitation/educational program with attention to speech/communication, use of sign language, motor development, cognition, and social skills; ACTH for infantile spasms; routine antiepileptic drugs (AEDs) for other seizure types; special feeding techniques and/or devices including gastrostomy tube for feeding difficulties; standard pharmacotherapy for non-compaction cardiomyopathy; standard care for eye/vision problems, skeletal anomalies, hearing loss, hypothyroidism, and renal abnormalities.

Surveillance: Systematic follow up for adjustment of rehabilitation/education and medical treatment as needs change over time.

Genetic counseling: 1p36 deletion syndrome is caused by deletion of the 1p36 chromosome region by one of several genetic mechanisms. Approximately 52% of individuals with 1p36 deletion syndrome have a de novo terminal 1p36 deletion, approximately 29% have an interstitial deletion, approximately 12% have more complex chromosome rearrangements that may include more than one 1p36 deletion or a 1p36 deletion with a 1p36 duplication, and approximately 7% have a derivative chromosome 1 (in which the 1p telomeric region is replaced by another chromosome end). Risks to family members depend on the mechanism of origin of the deletion. Prenatal testing is possible for families who have had a child with 1p36 deletion syndrome or a family in which one parent is a known carrier of a chromosome rearrangement involving 1p36.