PMC9822525_01
Clinical findings. (A) Pedigree chart of the patient's family. All family members underwent DNA analyses. (B) The face of a patient with microcephaly, thick eyebrows, long eyelashes, deep-set eyes, right ptosis, mildly upslanted palpebral fissures, broad nasal tip, prominent nasal bridge, low-set and malformed ears, micrognathia, and overjet. (C) Three-dimensional reconstruction image of a bone computed tomography scan shows pectus excavatum and scoliosis. (D) Long slender fingers (arachnodactyly). (E) Brain magnetic resonance imaging reveals diffuse and mild cortical atrophy and right-sided deviation of the cerebrum. (F) Images of cerebral blood flow with single-photon emission CT using N-isopropyl-p-[123I] iodoamphetamine (IMP-SPECT). The Z-score shifts to red (6) as the degree of the decrease in the cerebral blood flow that is larger than that of an age-matched normal database. IMP-SPECT reveals a decreased blood flow in the right medial occipital cortex, left lateral occipital cortex, and bilateral anterior and left infero-posterior cerebellum.
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FIG1
His parents and sister are alive and well without any dysmorphism (Figure 1A). He had dysmorphic facial features (Figure 1B), including thick eyebrows, long eyelashes, deep-set eyes, right ptosis, mild upslanted palpebral fissures, broad nasal tip, prominent nasal bridge, low-set and malformed ears, micrognathia, and overjet. Further, he had a slender body with pectus excavatum, scoliosis (Figure 1C), and long slender fingers (arachnodactyly) (Figure 1D). Brain magnetic resonance imaging revealed diffuse and mild cortical atrophy and right-sided deviation of the cerebrum (Figure 1E). Single-photon emission computed tomography using N-isopropyl-p-[123I] iodoamphetamine (IMP-SPECT) revealed hypoperfusion in the right medial occipital cortex, left lateral occipital cortex, and bilateral anterior and left infero-posterior cerebellum (Figure 1F).
Genetic testing. (A) Integrative Genomics Viewer shows NM_001347721 (DYRK1A):c.848dup pathogenic variant in the patient. His parents and sister did not carry this variant, indicating a de novo status. (B) Sanger sequencing analysis of cloned cDNA from the patient's white blood cell. The results indicate a heterozygous duplication variant (box and black arrow) in exon 7 of the DYRK1A gene [c.848dup, p.(Asn283Lysfs*6)], introducing an early stop codon at six amino acids downstream from the altered codon.
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FIG2
As a result of the abovementioned analysis, the patient showed a novel heterozygous duplication variant (NM_001347721: c.848dup, p.(Asn283LysfsTer6)) in the coding region of exon 7 of the DYRK1A gene (Figure 2).