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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Genetics

Genetics & Understanding Your Child's Genetic Report

At a Glance

Mowat-Wilson syndrome is caused by a mutation or deletion in one copy of the ZEB2 gene. Your child's genetic report will detail this change using terms like 'de novo' to indicate the mutation is new, and 'pathogenic' to confirm it is the cause of their diagnosis.

A genetic report can feel like it was written in another language. However, these documents contain the blueprint for understanding your child’s diagnosis. Mowat-Wilson Syndrome (MWS) is caused by the haploinsufficiency of the ZEB2 gene—meaning the body has only one working copy instead of two [1][2].

Decoding the Terminology

When you look at your child’s report, you will likely see several of these standardized terms:

  • Pathogenic or Likely Pathogenic: This means the lab is confident that this specific genetic change is the cause of your child’s medical condition [3][4].
  • Heterozygous: This confirms that the change is only on one of the two copies of the ZEB2 gene [5][6].
  • De Novo: This indicates the mutation is “new” in the child and was not inherited from either parent [7][8].
  • Deletion: A piece of the genetic code is missing. This can range from a tiny part of the gene to a large section of the chromosome [9].
  • Missense: A single “letter” in the genetic code is swapped for another. While some missense changes cause classic MWS, others may lead to milder or different symptoms [10][11].

How the Diagnosis is Found

Two types of tests are most commonly used to diagnose MWS:

  1. Chromosomal Microarray (CMA): This test is excellent at finding “large-scale” changes, like a deletion of the entire ZEB2 gene or the surrounding 2q22.3 region [12][13].
  2. Whole Exome Sequencing (WES): This test “spells out” the genes. It is necessary to find “small-scale” changes, like missense mutations or tiny deletions inside the gene that a microarray would miss [13][14].

Genotype-Phenotype Correlation: Does the Mutation Type Matter?

Doctors look at genotype-phenotype correlation to see if the specific type of mutation (genotype) predicts the severity of the symptoms (phenotype).

  • Large Deletions: Generally, larger deletions that involve the ZEB2 gene and neighboring genes on the chromosome are associated with more severe developmental and medical challenges [15][16].
  • Small Intragenic Mutations: Mutations located inside the gene vary. Some, especially those in certain areas like Exon 8, are linked to more multi-organ involvement [17][16].
  • Mosaicism: In rare cases, a child may have the mutation in only some of their cells, not all of them. This is called mosaicism and often results in a milder clinical presentation [18].

Your Genetic Report Checklist

A complete genetic report for MWS should include the following details. If any are missing, ask your genetic counselor for clarification:

  • [ ] Gene Name: Specifically mentions ZEB2.
  • [ ] Classification: Labeled as Pathogenic or Likely Pathogenic.
  • [ ] Variant Type: Specifies if it is a deletion, missense, nonsense, or frameshift mutation.
  • [ ] Location: Lists the specific coordinates or exon number (e.g., c.1027C>T or p.Arg343*).
  • [ ] Zygosity: Confirms the variant is heterozygous.
  • [ ] Inheritance: Notes if the variant is de novo (requires parental testing to confirm).

Back to the Beginning

Common questions in this guide

What does a 'de novo' mutation mean for Mowat-Wilson syndrome?
A de novo mutation indicates that the genetic change is brand new in your child and was not inherited from either parent. Doctors typically recommend testing both parents to confirm this status.
What is the role of the ZEB2 gene in MWS?
The ZEB2 gene provides crucial instructions for development. Mowat-Wilson syndrome occurs when there is a haploinsufficiency, meaning the body only has one working copy of the ZEB2 gene instead of the normal two.
Why do doctors use both microarrays and whole exome sequencing?
A chromosomal microarray detects large-scale genetic changes, like an entire missing section of the ZEB2 gene. Whole exome sequencing looks closer to spell out the gene's letters, finding tiny mistakes that a microarray would miss.
Does the type of ZEB2 mutation affect my child's symptoms?
Yes, the specific type and size of the genetic change can influence symptoms. Large gene deletions generally cause more severe developmental and medical challenges, while cases with mosaicism often result in milder symptoms.
What does 'Likely Pathogenic' mean on a genetic report?
When a variant is labeled 'pathogenic' or 'likely pathogenic', it means the genetic testing laboratory is highly confident that this specific genetic change is the definitive cause of your child's medical condition.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.The report says this variant is 'Likely Pathogenic'—does that provide enough certainty for a definitive MWS diagnosis?
  2. 2.Does the specific location of the mutation (like Exon 8) suggest my child might have more multi-organ involvement?
  3. 3.Since the report shows a large 2q22 deletion, are there other genes near ZEB2 that were also lost?
  4. 4.If my child’s results suggest mosaicism, what does that mean for their individual prognosis and our family planning?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
  1. 1

    A novel nonsense mutation of ZEB2 gene in a Chinese patient with Mowat-Wilson syndrome.

    Hu Y, Peng Q, Ma K, et al.

    Journal of clinical laboratory analysis 2020; (34(9)):e23413 doi:10.1002/jcla.23413.

    PMID: 32519765
  2. 2

    [Prenatal diagnosis of a fetus with Mowat-Wilson syndrome].

    Hu R, Luo X, Li Y, et al.

    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2019; (36(12)):1203-1205 doi:10.3760/cma.j.issn.1003-9406.2019.12.013.

    PMID: 31813148
  3. 3

    [BCL11B associated disorder a case report in Mexican population. Case report].

    Crisanto-López IE, Saldaña-Guerrer MP, Hernández-Camacho RM, Castro-Coyotl DM

    Revista medica del Instituto Mexicano del Seguro Social 2024; (62(6)):1-7.

    PMID: 39570871
  4. 4

    A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene.

    Zanotta N, Panzeri E, Minghetti S, et al.

    Seizure 2024; (116()):151-155 doi:10.1016/j.seizure.2023.01.015.

    PMID: 36710240
  5. 5

    Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

    Sarı A, Bodakçi E, Armağan B, et al.

    Turkish journal of medical sciences 2021; (51(4)):1695-1701 doi:10.3906/sag-2011-273.

    PMID: 33726481
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    Clinico-Radiological Phenotype of UBTF c.628G>A Pathogenic Variant-Related Neurodegeneration in Childhood: A Case Report and Literature Review

    Chi CS, Lee HF, Tsai CR

    Brain sciences 2022; (12(9)) doi:10.3390/brainsci12091262.

    PMID: 36138999
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    A novel Mecom gene mutation associated with amegakaryocytic thrombocytopenia in a premature infant.

    Deliloğlu B, Tüfekçi Ö, Tüzün F, et al.

    The Turkish journal of pediatrics 2022; (64(4)):736-740.

    PMID: 36082647
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    GNAO1-associated epileptic encephalopathy and movement disorders: c.607G>A variant represents a probable mutation hotspot with a distinct phenotype.

    Arya R, Spaeth C, Gilbert DL, et al.

    Epileptic disorders : international epilepsy journal with videotape 2017; (19(1)):67-75 doi:10.1684/epd.2017.0888.

    PMID: 28202424
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    Exome-first approach identified novel INDELs and gene deletions in Mowat-Wilson Syndrome patients.

    Gosso MF, Rohr C, Brun B, et al.

    Human genome variation 2018; (5()):21 doi:10.1038/s41439-018-0021-y.

    PMID: 30083364
  10. 10

    Subtle phenotypes of Mowat-Wilson syndrome in a patient with a novel ZEB2 C-ZF domain variant.

    Kuroda Y, Naruto T, Kurosawa K

    American journal of medical genetics. Part A 2024; (194(12)):e63822 doi:10.1002/ajmg.a.63822.

    PMID: 39023215
  11. 11

    Early Infantile Epileptic Encephalopathy with a de novo variant in ZEB2 identified by exome sequencing.

    Babkina N, Deignan JL, Lee H, et al.

    European journal of medical genetics 2016; (59(2)):70-4.

    PMID: 26721324
  12. 12

    Prenatal Diagnosis and Pregnancy Outcomes of Fetuses With Orofacial Cleft: A Retrospective Cohort Study in Two Centres in Hong Kong.

    Li YY, Tse WT, Kong CW, et al.

    The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 2024; (61(3)):391-399 doi:10.1177/10556656221128436.

    PMID: 36128746
  13. 13

    Copy number variants calling from WES data through eXome hidden Markov model (XHMM) identifies additional 2.5% pathogenic genomic imbalances smaller than 30 kb undetected by array-CGH.

    Tisserant E, Vitobello A, Callegarin D, et al.

    Annals of human genetics 2022; (86(4)):171-180 doi:10.1111/ahg.12459.

    PMID: 35141892
  14. 14

    Identification of Copy Number Variation by Array-CGH in Portuguese Children and Adolescents Diagnosed with Autism Spectrum Disorders.

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    Neuropediatrics 2019; (50(6)):367-377 doi:10.1055/s-0039-1694797.

    PMID: 31398764
  15. 15

    Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care.

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  16. 16

    Genotype-phenotype analysis in Mowat-Wilson syndrome associated with two novel and two recurrent variants.

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  17. 17

    ZEB2 Gene Pathogenic Variants Across Protein-Coding Regions and Impact on Clinical Manifestations: A Review.

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  18. 18

    [Clinical and genetic analysis of a patient with Mowat-Wilson syndrome].

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    PMID: 33974257

This page explains Mowat-Wilson Syndrome genetics for educational purposes. Your genetic counselor or pediatrician is the best source for interpreting your child's specific genetic testing report.

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