Background: Imagawa-Matsumoto syndrome (IMMAS; MIM #618786) is a rare autosomal dominant disorder caused by pathogenic variants in the SUZ12 gene on chromosome 17q11. First described in 2017, fewer than 15 cases have been reported worldwide. The syndrome is characterised by postnatal overgrowth, dysmorphic facial features, variable musculoskeletal abnormalities, and developmental delay/ intellectual disability. Given the broad phenotypic variability and overlap with other overgrowth conditions, diagnosis requires high clinical suspicion and genetic confirmation. Case Report: We report a 3-year-old male referred to our neurodevelopmental outpatient clinic for speech delay. He was born to non-consanguineous parents, with large for gestational age weight (birth weight: 4320g (P94; +1, 60 SDS). Clinical examination revealed dysmorphic features, including a prominent forehead, mild bilateral ectropion, anteverted nares, a prominent philtrum, slightly downslanting palpebral fissures, tapering fingers, and generalized hirsutism. Height and weight exceeded the 95th percentile (+1. 75 SD and +2. 84 SD, respectively), with a head circumference of 52 cm (+1. 57 SD; P94). Developmental assessment revealed global developmental delay, predominantly affecting expressive language, with additional deficits in fine and gross motor skills. Griffiths’ scale showed a global developmental quotient of 63. 2. He was referred to a genetics consultation and started speech and occupational therapy. Cytogenetic analysis and FMR1 testing were normal. Array-CGH identified a duplication at 3q29 (chr3: 197289694₁97590232) involving DLG1 and BDH1, inherited from a healthy parent and classified as a variant of uncertain significance. Subsequent targeted neurodevelopmental panel testing revealed a de novo heterozygous variant in SUZ12 (NM₀15355. 4: c. 1150₁151del), classified as probably pathogenic. Neurodevelopmental progress was favourable: he acquired reading and writing skills in the first year of schooling, performs basic calculations, and maintains autonomy. At 7 years, WISC-III demonstrated an IQ of 63. Discussion: IMMAS demonstrates considerable phenotypic heterogeneity, complicating clinical diagnosis. The identified SUZ12 variant, characteristic dysmorphic features, and global developmental delay support the diagnosis. This case highlights a favourable neurodevelopmental trajectory facilitated by early therapeutic intervention. Speech and occupational therapy were central in promoting cognitive, linguistic, and functional development. Nevertheless, his evaluated IQ was lower than expected, highlighting a discrepancy between psychometric testing and functional achievements and underscoring the importance of critical interpretation of cognitive assessments. This report expands the clinical spectrum of IMMAS and reinforces the role of comprehensive genetic testing in children presenting with dysmorphic features, overgrowth, and developmental delay. It additionally underscores the importance of early intervention in enhancing neurodevelopmental outcomes. Learning Points: IMMAS is a rare, recently described syndrome caused by pathogenic SUZ12 variants. Clinical presentation is variable, and diagnosis requires genetic confirmation. Early intervention can significantly improve neurodevelopmental outcomes. A comprehensive clinical evaluation is essential in assessing intellectual functioning. This report adds to the limited literature, improving the clinical characterization of the syndrome.
Ferreira et al. (Thu,) studied this question.