De Novo Mutation in KMT2C Manifesting as Kleefstra Syndrome 2: Case Report and Literature Review.
Maria Anna SianoIlaria De MaggioRoberta PetilloDario CocciadiferroEmanuele AgoliniMassimo MajoloAntonio NovelliMatteo Della MonicaCarmelo PiscopoPublished in: Pediatric reports (2022)
Diagnosis of pediatric intellectual disability (ID) can be difficult because it is due to a vast number of established and novel causes. Here, we described a full-term female infant affected by Kleefstra syndrome-2 presenting with neurodevelopmental disorder, a history of hypotonia and minor face anomalies. A systematic literature review was also performed. The patient was a 6-year-old Caucasian female. In the family history there was no intellectual disability or genetic conditions. Auxological parameters at birth were adequate for gestational age. Clinical evaluation at 6 months revealed hypotonia and, successively, delay in the acquisition of the stages of psychomotor development. Auditory, visual, somatosensory, and motor-evoked potentials were normal. A brain MRI, performed at 9 months, showed minimal gliotic changes in bilateral occipital periventricular white matter. Neuropsychiatric control, performed at 5 years, established a definitive diagnosis of childhood autism and developmental delay. Molecular analysis of the exome revealed a novel KMT2C missense variant: c.9244C > T (p.Pro3082Ser) at a heterozygous state, giving her a diagnosis of Kleefstra syndrome 2. Parents did not show the variant. Literature review (four retrieved eligible studies, 10 patients) showed that all individuals had mild, moderate, or severe ID; language and motor delay; and autism. Short stature, microcephaly, childhood hypotonia and plagiocephaly were also present. Conclusion. Kleefstra syndrome 2 is a difficult diagnosis of a rare condition with a high clinical phenotypic heterogeneity. This study suggests that it must be taken in account in the work-up of an orphan diagnosis of intellectual disability and/or autism spectrum disorder.
Keyphrases
- intellectual disability
- autism spectrum disorder
- case report
- gestational age
- attention deficit hyperactivity disorder
- white matter
- clinical evaluation
- early onset
- single cell
- squamous cell carcinoma
- preterm birth
- birth weight
- gene expression
- end stage renal disease
- multiple sclerosis
- pregnant women
- genome wide
- high intensity
- working memory
- zika virus
- ejection fraction
- copy number
- magnetic resonance
- body mass index
- childhood cancer
- blood brain barrier
- functional connectivity
- resting state
- drug induced
- single molecule