New Case of Homozygous Pathogenic Variants in TBCK and DHCR7 Genes
Keywords:
Muscle Hypotonia, Microcephaly, Intellectual Disability, Genetic PhenomenaAbstract
Introduction: Variants in the TBCK gene are associated with Infantile Hypotonia with Psychomotor Retardation and Characteristic Facies Type 3 (IHPRF3) syndrome. The DHCR7 gene is associated with Smith-Lemli-Opitz syndrome (SLOS).
Objective: To describe a new case of homozygous pathogenic variants in the TBCK and DHCR7 genes.
Methods: A 15-month-old male, the first child of consanguineous parents, with a family history of first-degree cognitive delay (mother) and fourth-degree relatives. He was born by cesarean section at 38 weeks. Brain MRI showed bilateral temporal-occipital alteration of migration and post-migration, reduced posterior fossa size, and right posterior plagiocephaly. He had a weight of -1.84 SD, height -1.99 SD, head circumference -2.13 SD, right plagiocephaly, non-fixed gaze, unfolded ears, left ear rotated backward, low implantation, small nose, sunken eyes, shallow orbits, mild pectus excavatum, hydrocele, bilateral simian crease, hypotonia, and no head control.
Findings: Normal karyotype, clinical exome sequencing revealed a homozygous pathogenic variant in the TBCK gene (DNA variant c.412dupT, p.Tyr138fs*8) of probable clinical significance. In the HUWE1 gene, there was a hemizygous variant (c.10514C>T, p.Pro3505Leu) of uncertain clinical significance, with in silico predictors indicating a benign variant. In the DHCR7 gene, there was a homozygous variant (c.506C>T, p.Ser169Leu) of uncertain clinical significance.
Discussion: Shared features include developmental delay, hypotonia, and microcephaly. For IHPRF3, facial features, speech delay, and brain MRI findings are characteristic, while for SLOS, a short nose and low stature are common.
Conclusions: Our patient has two pathogenic variants (TBCK and DHCR7).
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References
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