Rothmund-Thomson syndrome type 1 caused by biallelic ANAPC1 gene mutations.

Area of Science:

• Genetics
• Dermatology
• Pediatrics

Background:

• Rare syndromic skin disorders present significant diagnostic challenges.
• Accurate genetic diagnosis is essential for identifying specific subtypes of Robertsonian translocation syndrome (RTS) and associated risks.

Observation:

• A 14-month-old boy presented with poikiloderma, facial dysmorphism, atrichia, nail dysplasia, cryptorchidism, and delayed psychomotor development.
• Initial genetic analysis excluded RECQL4 mutations associated with RTS type 2.

Findings:

• Exome sequencing and array comparative genomic hybridization (array-CGH) identified a novel combination of a recurrent intronic mutation and a deletion of the ANAPC1 gene, confirming Robertsonian translocation syndrome type 1 (RTS1).
• The deletion on chromosome 2q13, spanning 1.7 megabases, is associated with 2q13 microdeletion syndrome, developmental delay, autism, and facial dysmorphism.
• The genetic findings explain both the RTS1 features and the patient's developmental delay.

Implications:

• This case underscores the importance of comprehensive clinical evaluation preceding genetic testing for RTS1, as a recurrent intronic ANAPC1 mutation can be overlooked.
• Accurate genetic subtyping of RTS is critical for managing associated risks, such as the high likelihood of juvenile cataracts in RTS1, necessitating regular ophthalmologic monitoring.