<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Van Maldergem syndrome (VMLDS) is a recessive disease which affects multiple organs including the face, ear, and limb extremities. It can be caused by pathogenic variants in either the gene DCHS1 or FAT4. Diagnosis of VMLDS is complicated, especially regarding its similarity of symptoms to Hennekam syndrome, another disorder caused by FAT4 variants. Reported patients are two infantile siblings with multiple congenital anomalies, who deceased without clinical diagnosis. Whole exome sequencing was exploited for expanded carrier screening (ECS) of their parents, which revealed a novel splicing variant in the gene FAT4, NM_024582.6: c.7018+1G>A. In silico analysis of the variant indicates loss of canonical donor splice site of intron 6. This variant is classified as pathogenic based on ACMG criteria. Reverse phenotyping of patients resulted in likely diagnosis of VMLDS2. This study reaffirms the possibility of using ECS, leading to the genetic diagnosis of a rare disease with complicated clinical features.</p>
</abstract>

Van Maldergem syndrome (VMLDS) is a recessive disease which affects multiple organs including the face, ear, and limb extremities. It can be caused by pathogenic variants in either the gene DCHS1 or FAT4. Diagnosis of VMLDS is complicated, especially regarding its similarity of symptoms to Hennekam syndrome, another disorder caused by FAT4 variants. Reported patients are two infantile siblings with multiple congenital anomalies, who deceased without clinical diagnosis. Whole exome sequencing was exploited for expanded carrier screening (ECS) of their parents, which revealed a novel splicing variant in the gene FAT4, NM_024582.6: c.7018+1G>A. In silico analysis of the variant indicates loss of canonical donor splice site of intron 6. This variant is classified as pathogenic based on ACMG criteria. Reverse phenotyping of patients resulted in likely diagnosis of VMLDS2. This study reaffirms the possibility of using ECS, leading to the genetic diagnosis of a rare disease with complicated clinical features.

Use of expanded carrier screening for retrospective diagnosis of two deceased siblings with Van Maldergem syndrome 2: case report

Department of Medical Genetics and Molecular Biology, School of Medicine

Department of Oncology and Stem Cell Transplantation, Shariati Hospital, School of Medicine

Department of Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, School of Medicine

Asian Biomedicine

This work is licensed under the Creative Commons Attribution 4.0 International License.

Van Maldergem syndrome (VMLDS) is a recessive disease which affects multiple organs including the face, ear, and limb extremities. It can be caused by...

Use of expanded carrier screening for retrospective diagnosis of two deceased siblings with Van Maldergem syndrome 2: case report

Article Category: Clinical vignettes

Data publikacji: 01 sie 2023

Zakres stron: 322 - 328

DOI: https://doi.org/10.2478/abm-2022-0036

Słowa kluczowe
carrier screening, exome sequencing, Van Maldergem syndrome, FAT4, congenital anomalies

© 2023 Nasim Rahmani et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Use of expanded carrier screening for retrospective diagnosis of two deceased siblings with Van Maldergem syndrome 2: case report

Article Category: Clinical vignettes

Data publikacji: 01 sie 2023

Zakres stron: 322 - 328

DOI: https://doi.org/10.2478/abm-2022-0036

Słowa kluczowecarrier screening, exome sequencing, Van Maldergem syndrome, FAT4, congenital anomalies

© 2023 Nasim Rahmani et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Słowa kluczowe
carrier screening, exome sequencing, Van Maldergem syndrome, FAT4, congenital anomalies