Pontocerebellar Hypoplasia Type 11 Case with a Novel Variant of TBC1D23 Gene: Case Report and Literature Review.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurological disorders that primarily affect the cerebellum and brainstem within the central nervous system, and homozygous pathogenic variants of TBC1D23 gene cause PCH type 11 (PCH-11), an extremely rare non-progressive subtype of PCH. Here, we report a PCH-11 case with a novel homozygous variant in TBC1D23 gene and present a summary of PCH-11 cases in the literature. A six-year-old boy was first admitted to our clinic at the age of three with global developmental delay and gait instability. His medical history was unremarkable, aside from parental consanguinity. Physical examination revealed microcephaly, limited eye contact, hyporeflexia and ataxia. Dysmorphic facial features and bilateral talipes equinovarus were also present. Brain magnetic resonance imaging (MRI) revealed pontocerebellar hypoplasia and mild cerebral atrophy. Exome sequencing identified a homozygous likely pathogenic variant in TBC1D23 gene ([NM_018309.5]: c.1858 C > T p.[Arg620*]), and he was diagnosed with PCH-11. To our knowledge, 21 PCH-11 cases associated with 12 different TBC1D23 gene variants have been reported in the literature, including our patient. The severity of clinical features varied considerably among cases, with the most common findings being global developmental delay, intellectual disability and behavioral/psychiatric problems. Microcephaly, muscle tone abnormalities and abnormal cerebellar signs were the most common reported examination findings. Pontocerebellar hypoplasia and corpus callosum agenesis/hypoplasia were the most frequent neuroimaging findings. PCH-11 is a relatively recently identified, extremely rare disorder about which our knowledge of PCH-11 is quite limited. More studies are needed to understand the pathogenesis and course of the disorder.