Phenotypic manifestations of C5orf42 pathogenic variants
Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern caused by pathogenic variants in at least 35 genes, all encoding structures of the primary cilium involved in signaling pathways that coordinate the normal development of the kidneys, retina, brain, liv...
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| Format: | Article |
| Language: | English |
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Amaltea Medical Publishing House
2022-03-01
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| Series: | Romanian Journal of Pediatrics |
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| Online Access: | https://rjp.com.ro/articles/2022.1/RJP_2022_1_Art-08.pdf |
| _version_ | 1818518879513608192 |
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| author | Elena-Silvia Shelby Relu Cocos Madalina Cristina Leanca Andrada Mirea Diana Barca |
| author_facet | Elena-Silvia Shelby Relu Cocos Madalina Cristina Leanca Andrada Mirea Diana Barca |
| author_sort | Elena-Silvia Shelby |
| collection | DOAJ |
| description | Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern caused by pathogenic variants in at least 35 genes, all encoding structures of the primary cilium involved in signaling pathways that coordinate the normal development of the kidneys, retina, brain, liver and skeletal system. The symptoms can consist in cystic renal disease and renal dystrophy, oculomotor apraxia, global developmental delay, hypotonia evolving into ataxia, skeletal and endocrine abnormalities, abnormal breathing patterns and congenital hepatic fibrosis, with the neurologic and ophthalmologic manifestations appearing early in life. The diagnostic hallmark is “the molar tooth sign”, a malformation of the brainstem and cerebellum easily identifiable using brain imaging techniques. As Joubert syndrome is a highly heterogeneous disease with a large type of phenotypes, it is oftentimes underdiagnosed. This article presents a case of Joubert syndrome type 17, a rare syndrome with many features overlapping orofaciodigital syndrome type VI. Adding to the rarity of this disease, our patient is homozygous and heterozygous for two pathogenic variants in C5orf42, with one located upstream of the other, thus manifesting the phenotype of a compound heterozygous in this gene. We believe that the presentation of this rare syndrome is useful to the pediatric practice by facilitating a fast diagnosis of these patients, which helps provide genetic counselling to the patients and their families. |
| first_indexed | 2024-12-11T01:16:19Z |
| format | Article |
| id | doaj.art-07627fab7021484c96202099da0625f9 |
| institution | Directory Open Access Journal |
| issn | 1454-0398 2069-6175 |
| language | English |
| last_indexed | 2024-12-11T01:16:19Z |
| publishDate | 2022-03-01 |
| publisher | Amaltea Medical Publishing House |
| record_format | Article |
| series | Romanian Journal of Pediatrics |
| spelling | doaj.art-07627fab7021484c96202099da0625f92022-12-22T01:25:52ZengAmaltea Medical Publishing HouseRomanian Journal of Pediatrics1454-03982069-61752022-03-01711394610.37897/RJP.2022.1.8Phenotypic manifestations of C5orf42 pathogenic variantsElena-Silvia Shelby0Relu Cocos1Madalina Cristina Leanca2Andrada Mirea3Diana Barca4“Dr. Nicolae Robanescu” National Clinical Center for Children’s Neurorehabilitation, Bucharest, RomaniaChair of Medical Genetics, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania“Dr. Nicolae Robanescu” National Clinical Center for Children’s Neurorehabilitation, Bucharest, Romania“Dr. Nicolae Robanescu” National Clinical Center for Children’s Neurorehabilitation, Bucharest, Romania; Faculty of Midwifery and Nursing, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania“Prof. Dr. Alexandru Obregia” Psychiatry Hospital, Bucharest, RomaniaJoubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern caused by pathogenic variants in at least 35 genes, all encoding structures of the primary cilium involved in signaling pathways that coordinate the normal development of the kidneys, retina, brain, liver and skeletal system. The symptoms can consist in cystic renal disease and renal dystrophy, oculomotor apraxia, global developmental delay, hypotonia evolving into ataxia, skeletal and endocrine abnormalities, abnormal breathing patterns and congenital hepatic fibrosis, with the neurologic and ophthalmologic manifestations appearing early in life. The diagnostic hallmark is “the molar tooth sign”, a malformation of the brainstem and cerebellum easily identifiable using brain imaging techniques. As Joubert syndrome is a highly heterogeneous disease with a large type of phenotypes, it is oftentimes underdiagnosed. This article presents a case of Joubert syndrome type 17, a rare syndrome with many features overlapping orofaciodigital syndrome type VI. Adding to the rarity of this disease, our patient is homozygous and heterozygous for two pathogenic variants in C5orf42, with one located upstream of the other, thus manifesting the phenotype of a compound heterozygous in this gene. We believe that the presentation of this rare syndrome is useful to the pediatric practice by facilitating a fast diagnosis of these patients, which helps provide genetic counselling to the patients and their families.https://rjp.com.ro/articles/2022.1/RJP_2022_1_Art-08.pdfjoubert syndrome type 17c5orf42compound heterozygous |
| spellingShingle | Elena-Silvia Shelby Relu Cocos Madalina Cristina Leanca Andrada Mirea Diana Barca Phenotypic manifestations of C5orf42 pathogenic variants Romanian Journal of Pediatrics joubert syndrome type 17 c5orf42 compound heterozygous |
| title | Phenotypic manifestations of C5orf42 pathogenic variants |
| title_full | Phenotypic manifestations of C5orf42 pathogenic variants |
| title_fullStr | Phenotypic manifestations of C5orf42 pathogenic variants |
| title_full_unstemmed | Phenotypic manifestations of C5orf42 pathogenic variants |
| title_short | Phenotypic manifestations of C5orf42 pathogenic variants |
| title_sort | phenotypic manifestations of c5orf42 pathogenic variants |
| topic | joubert syndrome type 17 c5orf42 compound heterozygous |
| url | https://rjp.com.ro/articles/2022.1/RJP_2022_1_Art-08.pdf |
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