Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study

Dilek Cavusoglu¹, Gulten Ozturk², Dilsad Turkdogan², Semra Hiz Kurul³, Uluc Yis³, Mustafa Komur⁴, Faruk Incecik⁵, Bulent Kara⁶, Turkan Sahin⁷, Olcay Unver², Cengiz Dilber⁸, Gulen Gul Mert⁵, Cagatay Gunay³, Gamze Sarikaya Uzan³, Ozlem Ersoy⁴, Yavuz Oktay⁹, Serdar Mermer¹⁰, Gokcen Oz Tuncer¹¹, Olcay Gungor¹², Gul Demet Kaya Ozcora¹³, Ugur Gumus¹⁴, Ozlem Sezer¹⁵, Gokhan Ozan Cetin¹⁶, Fatma Demir¹⁷, Arzu Yilmaz¹⁸, Gurkan Gurbuz¹⁹, Meral Topcu²⁰, Haluk Topaloglu²¹, Ahmet Cevdet Ceylan¹⁷, Serdar Ceylaner²², Joseph G Gleeson²³, Dilara Fusun Icagasioglu⁷, F Mujgan Sonmez^{24

25

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Affiliations

¹ Departments of Pediatric Neurology, Afyonkarahisar Health Sciences University, Afyon, Turkey.
² Departments of Pediatric Neurology, Marmara University, Istanbul, Turkey.
³ Departments of Pediatric Neurology, Dokuz Eylul University, Izmir, Turkey.
⁴ Departments of Pediatric Neurology, Mersin University, Mersin, Turkey.
⁵ Departments of Pediatric Neurology, Cukurova University, Adana, Turkey.
⁶ Departments of Pediatric Neurology, Kocaeli University, Kocaeli, Turkey.
⁷ Departments of Pediatric Neurology, Bezmialem Vakif University, Istanbul, Turkey.
⁸ Departments of Pediatric Neurology, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
⁹ Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey.
¹⁰ Departments of Medical Genetics, Mersin University, Mersin, Turkey.
¹¹ Departments of Pediatric Neurology, Ondokuz Mayıs University, Samsun, Turkey.
¹² Departments of Pediatric Neurology, Pamukkale University, Denizli, Turkey.
¹³ Departments of Pediatric Neurology, Hasan Kalyoncu University, Gaziantep, Turkey.
¹⁴ Departments of Medical Genetics, Dr Ersin Arslan Training and Research Hospital, Gaziantep, Turkey.
¹⁵ Departments of Medical Genetics, Samsun Training and Research Hospital, Samsun, Turkey.
¹⁶ Departments of Medical Genetics, Pamukkale University, Denizli, Turkey.
¹⁷ Departments of Medical Genetics, Ankara Bilkent City Hospital, Ankara, Turkey.
¹⁸ Departments of Pediatric Neurology, Ankara Training and Research Hospital, Ankara, Turkey.
¹⁹ Departments of Pediatric Neurology, Tekirdag Namik Kemal University, Tekirdag, Turkey.
²⁰ Departments of Pediatric Neurology, Hacettepe University,Retired Lecturer, Ankara, Turkey.
²¹ Departments of Pediatric Neurology, Yeditepe University, Istanbul, Turkey.
²² Intergen Genetic Research Center, Ankara, Turkey.
²³ Department of Neurosciences and Pediatrics, Rady Children's Institute for Genomic Medicine, Howard Hughes Medical Institute, University of California, La Jolla, San Diego, CA, USA.
²⁴ Departments of Pediatric Neurology, Department of Child Neurology, Karadeniz Technical University Medical Faculty, Retired Lecturer, Trabzon, Turkey. mjgsonmez@yahoo.com.
²⁵ Yuksek Ihtisas University, Faculty of Medicine, Ankara, Turkey. mjgsonmez@yahoo.com.
²⁶ , Aziziye Mah. Cinnah Cad. 102/3, Cankaya, Ankara, Türkiye. mjgsonmez@yahoo.com.

PMID: 38622473
PMCID: PMC11489189
DOI: 10.1007/s12311-024-01690-1

Multicenter Study

Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study

Dilek Cavusoglu et al. Cerebellum. 2024 Oct.

. 2024 Oct;23(5):1950-1965.

doi: 10.1007/s12311-024-01690-1. Epub 2024 Apr 15.

Authors

Affiliations

¹ Departments of Pediatric Neurology, Afyonkarahisar Health Sciences University, Afyon, Turkey.
² Departments of Pediatric Neurology, Marmara University, Istanbul, Turkey.
³ Departments of Pediatric Neurology, Dokuz Eylul University, Izmir, Turkey.
⁴ Departments of Pediatric Neurology, Mersin University, Mersin, Turkey.
⁵ Departments of Pediatric Neurology, Cukurova University, Adana, Turkey.
⁶ Departments of Pediatric Neurology, Kocaeli University, Kocaeli, Turkey.
⁷ Departments of Pediatric Neurology, Bezmialem Vakif University, Istanbul, Turkey.
⁸ Departments of Pediatric Neurology, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
⁹ Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey.
¹⁰ Departments of Medical Genetics, Mersin University, Mersin, Turkey.
¹¹ Departments of Pediatric Neurology, Ondokuz Mayıs University, Samsun, Turkey.
¹² Departments of Pediatric Neurology, Pamukkale University, Denizli, Turkey.
¹³ Departments of Pediatric Neurology, Hasan Kalyoncu University, Gaziantep, Turkey.
¹⁴ Departments of Medical Genetics, Dr Ersin Arslan Training and Research Hospital, Gaziantep, Turkey.
¹⁵ Departments of Medical Genetics, Samsun Training and Research Hospital, Samsun, Turkey.
¹⁶ Departments of Medical Genetics, Pamukkale University, Denizli, Turkey.
¹⁷ Departments of Medical Genetics, Ankara Bilkent City Hospital, Ankara, Turkey.
¹⁸ Departments of Pediatric Neurology, Ankara Training and Research Hospital, Ankara, Turkey.
¹⁹ Departments of Pediatric Neurology, Tekirdag Namik Kemal University, Tekirdag, Turkey.
²⁰ Departments of Pediatric Neurology, Hacettepe University,Retired Lecturer, Ankara, Turkey.
²¹ Departments of Pediatric Neurology, Yeditepe University, Istanbul, Turkey.
²² Intergen Genetic Research Center, Ankara, Turkey.
²³ Department of Neurosciences and Pediatrics, Rady Children's Institute for Genomic Medicine, Howard Hughes Medical Institute, University of California, La Jolla, San Diego, CA, USA.
²⁴ Departments of Pediatric Neurology, Department of Child Neurology, Karadeniz Technical University Medical Faculty, Retired Lecturer, Trabzon, Turkey. mjgsonmez@yahoo.com.
²⁵ Yuksek Ihtisas University, Faculty of Medicine, Ankara, Turkey. mjgsonmez@yahoo.com.
²⁶ , Aziziye Mah. Cinnah Cad. 102/3, Cankaya, Ankara, Türkiye. mjgsonmez@yahoo.com.

PMID: 38622473
PMCID: PMC11489189
DOI: 10.1007/s12311-024-01690-1

Abstract

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative disorders characterized by hypoplasia and degeneration of the cerebellum and pons. We aimed to identify the clinical, laboratory, and imaging findings of the patients with diagnosed PCH with confirmed genetic analysis. We collected available clinical data, laboratory, and imaging findings in our retrospective multicenter national study of 64 patients with PCH in Turkey. The genetic analysis included the whole-exome sequencing (WES), targeted next-generation sequencing (NGS), or single gene analysis. Sixty-four patients with PCH were 28 female (43.8%) and 36 (56.3%) male. The patients revealed homozygous mutation in 89.1%, consanguinity in 79.7%, pregnancy at term in 85.2%, microcephaly in 91.3%, psychomotor retardation in 98.4%, abnormal neurological findings in 100%, seizure in 63.8%, normal biochemistry and metabolic investigations in 92.2%, and dysmorphic findings in 51.2%. The missense mutation was found to be the most common variant type in all patients with PCH. It was detected as CLP1 (n = 17) was the most common PCH related gene. The homozygous missense variant c.419G > A (p.Arg140His) was identified in all patients with CLP1. Moreover, all patients showed the same homozygous missense variant c.919G > T (p.A307S) in TSEN54 group (n = 6). In Turkey, CLP1 was identified as the most common causative gene with the identical variant c.419G > A; p.Arg140His. The current study supports that genotype data on PCH leads to phenotypic variability over a wide phenotypic spectrum.

Keywords: CLP1; Genotype; Phenotype; Pontocerebellar Hypoplasia.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 3**
(a-d) Typical radiological findings shown—(a, b) dragonfly pattern (comparatively preserved vermis and atrophic cerebellar hemispheres) in one patient with TSEN54 gene. (c, d) brainstem appearance of figure of 8 on the brain MRI of one patient with AMPD2 gene

See this image and copyright information in PMC

References

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Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study

Affiliations

Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Supplementary concepts

LinkOut - more resources

Full Text Sources

Medical