Is MED13L-related intellectual disability a recognizable syndrome?

Pernille Mathiesen Tørring*, Martin Jakob Larsen, Charlotte Brasch-Andersen, Lotte Nylandsted Krogh, Maria Kibæk, Lone Laulund, Niels Illum, Ulrike Dunkhase-Heinl, Antje Wiesener, Bernt Popp, Giuseppe Marangi, Tina Duelund Hjortshøj, Jakob Ek, Ida Vogel, Naja Becher, Laura Roos, Marcella Zollino, Christina Ringmann Fagerberg

*Corresponding author for this work

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Abstract

Introduction: MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients. Materials and methods: In the search for genetic aberrations in individuals with ID, two of the patients were identified by chromosomal microarray analysis, and five by exome sequencing. One of the individuals, suspected of MED13L-related intellectual disability, based on clinical features, was identified by Sanger sequencing. Results: All 8 individuals had de novo MED13L aberrations, including two intragenic microdeletions, two frameshift, three nonsense variants, and one missense variant. Phenotypically, they all had intellectual disability, speech and motor delay, and features of the mouth (open mouth appearance, macroglossia, and/or macrostomia). Two individuals were diagnosed with autism, and one had autistic features. One had complex congenital heart defect, and one had persistent foramen ovale. The literature was reviewed with respect to clinical and dysmorphic features, and genetic aberrations. Conclusions: Even if most clinical features of MED13L-related intellectual disability are rather non-specific, the syndrome may be suspected in some individuals based on the association of developmental delay, speech impairment, bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance.

Original languageEnglish
JournalEuropean Journal of Medical Genetics
Volume62
Issue number2
Pages (from-to)129-136
ISSN1769-7212
DOIs
Publication statusPublished - Feb 2019

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Macrostomia
Macroglossia
Language Development Disorders
Foramen Ovale
Exome
Nose

Keywords

  • Developmental delay
  • Intellectual disability
  • MED13L
  • MED13L haploinsufficiency syndrome
  • MED13L-related intellectual disability

Cite this

@article{256b009008ad45f5ac4695dce8e86aa8,
title = "Is MED13L-related intellectual disability a recognizable syndrome?",
abstract = "Introduction: MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients. Materials and methods: In the search for genetic aberrations in individuals with ID, two of the patients were identified by chromosomal microarray analysis, and five by exome sequencing. One of the individuals, suspected of MED13L-related intellectual disability, based on clinical features, was identified by Sanger sequencing. Results: All 8 individuals had de novo MED13L aberrations, including two intragenic microdeletions, two frameshift, three nonsense variants, and one missense variant. Phenotypically, they all had intellectual disability, speech and motor delay, and features of the mouth (open mouth appearance, macroglossia, and/or macrostomia). Two individuals were diagnosed with autism, and one had autistic features. One had complex congenital heart defect, and one had persistent foramen ovale. The literature was reviewed with respect to clinical and dysmorphic features, and genetic aberrations. Conclusions: Even if most clinical features of MED13L-related intellectual disability are rather non-specific, the syndrome may be suspected in some individuals based on the association of developmental delay, speech impairment, bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance.",
keywords = "Developmental delay, Intellectual disability, MED13L, MED13L haploinsufficiency syndrome, MED13L-related intellectual disability",
author = "T{\o}rring, {Pernille Mathiesen} and Larsen, {Martin Jakob} and Charlotte Brasch-Andersen and Krogh, {Lotte Nylandsted} and Maria Kib{\ae}k and Lone Laulund and Niels Illum and Ulrike Dunkhase-Heinl and Antje Wiesener and Bernt Popp and Giuseppe Marangi and Hjortsh{\o}j, {Tina Duelund} and Jakob Ek and Ida Vogel and Naja Becher and Laura Roos and Marcella Zollino and Fagerberg, {Christina Ringmann}",
year = "2019",
month = "2",
doi = "10.1016/j.ejmg.2018.06.014",
language = "English",
volume = "62",
pages = "129--136",
journal = "European Journal of Medical Genetics",
issn = "1769-7212",
publisher = "Elsevier Masson",
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}

Is MED13L-related intellectual disability a recognizable syndrome? / Tørring, Pernille Mathiesen; Larsen, Martin Jakob; Brasch-Andersen, Charlotte; Krogh, Lotte Nylandsted; Kibæk, Maria; Laulund, Lone; Illum, Niels; Dunkhase-Heinl, Ulrike; Wiesener, Antje; Popp, Bernt; Marangi, Giuseppe; Hjortshøj, Tina Duelund; Ek, Jakob; Vogel, Ida; Becher, Naja; Roos, Laura; Zollino, Marcella; Fagerberg, Christina Ringmann.

In: European Journal of Medical Genetics, Vol. 62, No. 2, 02.2019, p. 129-136.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Is MED13L-related intellectual disability a recognizable syndrome?

AU - Tørring, Pernille Mathiesen

AU - Larsen, Martin Jakob

AU - Brasch-Andersen, Charlotte

AU - Krogh, Lotte Nylandsted

AU - Kibæk, Maria

AU - Laulund, Lone

AU - Illum, Niels

AU - Dunkhase-Heinl, Ulrike

AU - Wiesener, Antje

AU - Popp, Bernt

AU - Marangi, Giuseppe

AU - Hjortshøj, Tina Duelund

AU - Ek, Jakob

AU - Vogel, Ida

AU - Becher, Naja

AU - Roos, Laura

AU - Zollino, Marcella

AU - Fagerberg, Christina Ringmann

PY - 2019/2

Y1 - 2019/2

N2 - Introduction: MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients. Materials and methods: In the search for genetic aberrations in individuals with ID, two of the patients were identified by chromosomal microarray analysis, and five by exome sequencing. One of the individuals, suspected of MED13L-related intellectual disability, based on clinical features, was identified by Sanger sequencing. Results: All 8 individuals had de novo MED13L aberrations, including two intragenic microdeletions, two frameshift, three nonsense variants, and one missense variant. Phenotypically, they all had intellectual disability, speech and motor delay, and features of the mouth (open mouth appearance, macroglossia, and/or macrostomia). Two individuals were diagnosed with autism, and one had autistic features. One had complex congenital heart defect, and one had persistent foramen ovale. The literature was reviewed with respect to clinical and dysmorphic features, and genetic aberrations. Conclusions: Even if most clinical features of MED13L-related intellectual disability are rather non-specific, the syndrome may be suspected in some individuals based on the association of developmental delay, speech impairment, bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance.

AB - Introduction: MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients. Materials and methods: In the search for genetic aberrations in individuals with ID, two of the patients were identified by chromosomal microarray analysis, and five by exome sequencing. One of the individuals, suspected of MED13L-related intellectual disability, based on clinical features, was identified by Sanger sequencing. Results: All 8 individuals had de novo MED13L aberrations, including two intragenic microdeletions, two frameshift, three nonsense variants, and one missense variant. Phenotypically, they all had intellectual disability, speech and motor delay, and features of the mouth (open mouth appearance, macroglossia, and/or macrostomia). Two individuals were diagnosed with autism, and one had autistic features. One had complex congenital heart defect, and one had persistent foramen ovale. The literature was reviewed with respect to clinical and dysmorphic features, and genetic aberrations. Conclusions: Even if most clinical features of MED13L-related intellectual disability are rather non-specific, the syndrome may be suspected in some individuals based on the association of developmental delay, speech impairment, bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance.

KW - Developmental delay

KW - Intellectual disability

KW - MED13L

KW - MED13L haploinsufficiency syndrome

KW - MED13L-related intellectual disability

U2 - 10.1016/j.ejmg.2018.06.014

DO - 10.1016/j.ejmg.2018.06.014

M3 - Journal article

VL - 62

SP - 129

EP - 136

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

SN - 1769-7212

IS - 2

ER -