See the published version of this preprint at Orphanet Journal of Rare Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Livia Garavelli
Corresponding Author
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Background: Mowat–Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2,865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children.
Results: In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build.
Conclusions: These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.
Keywords
Mowat-Wilson syndrome, ZEB2, Growth charts, Weight, Length, Height, Head circumference, Body mass index, BMI.
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This is a list of supplementary files associated with this preprint. Click to download.
- Additional4Fig.RD2LENGTHHEIGHTFEMALES.tif
- ADDITIONAL8FIG.RD6HEADCIRCUMFERENCEFEMALES.tif
- Additionalfile2Table2rev20200501SGJMKLG.pdf
- Additional6Fig.RD4WEIGHTFEMALES.tif
- ADDITIONAL7FIG.RD5HEADCIRCUMFERENCEMALES.tif
- Additional5Fig.RD3WEIGHTMALES.tif
- Additional3.Fig.RD1LENGTHHEIGHTMALES.tif
- Additionalfile1Table1.docx
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CURRENT STATUS: Published
View the published article at Orphanet Journal of Rare Diseases.
Version 2
Posted 19 May, 2020
No community comments so far
Editorial decision: Accept
On 23 May, 2020
Reviewer #2 agreed
On 14 May, 2020
Review #2 received
Received 14 May, 2020
Reviewers invited
Invitations sent on 11 May, 2020
Reviewer #1 agreed
On 11 May, 2020
Review #1 received
Received 11 May, 2020
Editor assigned
On 06 May, 2020
Submission checks complete
On 05 May, 2020
Editor invited
On 05 May, 2020
No comments provided
Editorial decision: Minor revision
On 29 Apr, 2020
Review #2 received
Received 20 Apr, 2020
Reviewer #2 agreed
On 05 Apr, 2020
Review #1 received
Received 04 Apr, 2020
Reviewer #1 agreed
On 30 Mar, 2020
Reviewers invited
Invitations sent on 18 Mar, 2020
Editor assigned
On 13 Mar, 2020
First submitted
On 12 Mar, 2020
Submission checks complete
On 12 Mar, 2020
Editor invited
On 12 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
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See the published version of this preprint at Orphanet Journal of Rare Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Livia Garavelli
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Orphanet Journal of Rare Diseases.
Version 2
Posted 19 May, 2020
No community comments so far
Editorial decision: Accept
On 23 May, 2020
Reviewer #2 agreed
On 14 May, 2020
Review #2 received
Received 14 May, 2020
Reviewers invited
Invitations sent on 11 May, 2020
Reviewer #1 agreed
On 11 May, 2020
Review #1 received
Received 11 May, 2020
Editor assigned
On 06 May, 2020
Submission checks complete
On 05 May, 2020
Editor invited
On 05 May, 2020
No comments provided
Editorial decision: Minor revision
On 29 Apr, 2020
Review #2 received
Received 20 Apr, 2020
Reviewer #2 agreed
On 05 Apr, 2020
Review #1 received
Received 04 Apr, 2020
Reviewer #1 agreed
On 30 Mar, 2020
Reviewers invited
Invitations sent on 18 Mar, 2020
Editor assigned
On 13 Mar, 2020
First submitted
On 12 Mar, 2020
Submission checks complete
On 12 Mar, 2020
Editor invited
On 12 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Orphanet Journal of Rare Diseases.
Background: Mowat–Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2,865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children.
Results: In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build.
Conclusions: These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
This is a list of supplementary files associated with this preprint. Click to download.
- Additional4Fig.RD2LENGTHHEIGHTFEMALES.tif
- ADDITIONAL8FIG.RD6HEADCIRCUMFERENCEFEMALES.tif
- Additionalfile2Table2rev20200501SGJMKLG.pdf
- Additional6Fig.RD4WEIGHTFEMALES.tif
- ADDITIONAL7FIG.RD5HEADCIRCUMFERENCEMALES.tif
- Additional5Fig.RD3WEIGHTMALES.tif
- Additional3.Fig.RD1LENGTHHEIGHTMALES.tif
- Additionalfile1Table1.docx
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