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Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report
RATIONALE: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. PATIENT CONCERNS: We report the case of a polystigmatized 2-year-old boy h...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183750/ https://www.ncbi.nlm.nih.gov/pubmed/34087865 http://dx.doi.org/10.1097/MD.0000000000026136 |
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author | Pecimonova, Martina Radvanszky, Jan Smolak, David Budis, Jaroslav Lichvar, Michal Kristinova, Diana Rozova, Ivica Turna, Jan Szemes, Tomas |
author_facet | Pecimonova, Martina Radvanszky, Jan Smolak, David Budis, Jaroslav Lichvar, Michal Kristinova, Diana Rozova, Ivica Turna, Jan Szemes, Tomas |
author_sort | Pecimonova, Martina |
collection | PubMed |
description | RATIONALE: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. PATIENT CONCERNS: We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms. DIAGNOSES: The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband's genome that absented in any other analyzed family member, suggesting its de novo origin. INTERVENTIONS AND OUTCOMES: The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus. LESSONS: We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available. |
format | Online Article Text |
id | pubmed-8183750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-81837502021-06-07 Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report Pecimonova, Martina Radvanszky, Jan Smolak, David Budis, Jaroslav Lichvar, Michal Kristinova, Diana Rozova, Ivica Turna, Jan Szemes, Tomas Medicine (Baltimore) 3500 RATIONALE: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. PATIENT CONCERNS: We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms. DIAGNOSES: The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband's genome that absented in any other analyzed family member, suggesting its de novo origin. INTERVENTIONS AND OUTCOMES: The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus. LESSONS: We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available. Lippincott Williams & Wilkins 2021-06-04 /pmc/articles/PMC8183750/ /pubmed/34087865 http://dx.doi.org/10.1097/MD.0000000000026136 Text en Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | 3500 Pecimonova, Martina Radvanszky, Jan Smolak, David Budis, Jaroslav Lichvar, Michal Kristinova, Diana Rozova, Ivica Turna, Jan Szemes, Tomas Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report |
title | Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report |
title_full | Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report |
title_fullStr | Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report |
title_full_unstemmed | Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report |
title_short | Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report |
title_sort | admixed phenotype of nedd4l associated periventricular nodular heterotopia: a case report |
topic | 3500 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183750/ https://www.ncbi.nlm.nih.gov/pubmed/34087865 http://dx.doi.org/10.1097/MD.0000000000026136 |
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