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OP-066 A mutation leading to rare neurodevelopmental disorder unique to Turkish population
  1. Fulya Sibel Ekici Ibrahimoglu1,
  2. Peren Perk Yucel1,
  3. Ihsan Kafadar1,
  4. Aydeniz Aydın Gümüş2
  1. 1Department of Pediatric Neurology, University of Health Sciences, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
  2. 2Department of Medical Genetics, University of Health Sciences, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey


Aim Pontocerebellar hypoplasia type 10 (PCH type 10) is a rare autosomal recessive disorder caused by a mutation in the CLP1 gene, disrupting tRNA biogenesis and maturation. The resulting abnormal tRNA accumulation leads to neuronal death. In our case, the homozygous mutation (p.R140H) in the CLP1 gene caused PCH type 10, characterized by neurodevelopmental delay, progressive microcephaly, hypotonicity, refractory seizures, and mild CNS abnormalities.

Material and Method We report a 22-month-old male patient born from the consanguineous marriage of healthy parents of Turkish ancestry, received the diagnosis at the age of 19 months.

Results Follow-up appointments, insufficient growth was observed in the head circumference. At 11 months of age, when the patient was admitted to our clinic due to hypotonia, his motor development didn’t align with the WHO’s gross motor milestones. Inadequate head control, limited ability to sit with brief support, inability to crawl, and head circumference of 42 cm (SDS: -3.06) were observed. Facial features included high eyebrow arches, exotropia in the right eye, bifrontal narrowing, tented mouth (figure 1). Detailed medical history revealed muscle jerks, short-term tonic contractions, and spasm since the 6th month. EEG and cranial MRI imaging were performed. And based on the EEG results, antiepileptic medication was initiated. Cranial MRI showed ‘Bilateral posterior parieto-occipital white matter volume loss.’ (figure 2)Genetic testing (Whole Exome Sequencing) identified a pathogenic variant in the CLP1 gene (p.R140H). The patient also carried a heterozygous variant of uncertain significance (p.S487I) in the SCN8A gene. The patient was directed towards the rehabilitation process, involving various therapeutic modalities.

Abstract OP-066 Figure 1

a) Image of microcephaly, high eyebrow arches, exotropia, bifrontal narrowing, tented mouth, b) Cranial MRI showing ‘Bilateral posterior parieto-occipital white matter volume loss.’, c) No evidence of hypoplasia is observed in the pontocerebellar region.

Conclusions PCH type 10 differs from other PCH types as brain abnormalities are not prominently evident on imaging. Meticulous clinical observation is essential, particularly in children born from consanguineous marriages, presenting with neurodevelopmental delay, microcephaly, epilepsy, and abnormal facial features. Integrating genetic diagnostics, imaging studies, and a multidisciplinary rehabilitation approach aids in comprehensive patient management.

  • Pontocerebellar hypoplasia type 10
  • CLP1 gene mutation
  • Neurodevelopmental delay
  • Microcephaly

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