Novel compound heterozygous WDR35 variants in a Chinese patient associated with cranioectodermal dysplasia and ectopic testis: a case report and review of the literature.


Journal

BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804

Informations de publication

Date de publication:
18 08 2023
Historique:
received: 30 11 2022
accepted: 03 06 2023
medline: 21 8 2023
pubmed: 19 8 2023
entrez: 18 8 2023
Statut: epublish

Résumé

WDR35 variants are known to cause a rare autosomal recessive disorder-Cranioectodermal dysplasia (CED). The CED patients are commonly present with facial dysmorphisms (frontal bossing and low-set ears), sagittal craniosynostosis, growth retardation, dolichocephaly, skeletal deformities (brachydactyly, terminal hypoplasia of the fingers and narrow thorax), ectodermal abnormalities (sparse hair, and finger/toe nail dysplasia), nephronophthisis, retinal dystrophy and hepatic fibrosis. Diagnosis of CED can be difficult because it presents with high genetic heterogeneity. However, our understanding of the phenotype of CED caused by WDR35 variants could be more explicit, and the correlation between genotype and phenotype needs further improvement. We report a case of the first Chinses patient of CED caused by WDR35 variants, a 3-year-and-3-month-old patient, who was admitted to our hospital with frontal bossing, growth retardation, low set ears, dolichocephaly, sparse hair, and small limbs, abnormal renal function, and moderate anemia. The child showed a novel phenotype of the ectopic testis except for presenting typical CED characteristics, and he was identified with novel compound heterozygous WDR35 variants (c.2590 C > T, p.Gln864* and c.2408_2416del, p.Asn803_Ala805del; NM_001006657). He was given iron succinate and erythropoietin to improve anemia and to inhibit repeated metabolic acidosis and hyperkalemia through acid correction, diuretic, and potassium-lowering treatments. The parents refused to accept renal replacement therapy for their child and were discharged voluntarily. This is the first reported case of the WDR35 variants that can lead to CED and ectopic testis, which is also the first Chinese patient associated with WDR35 variants. This study expands our understanding of genotype-phenotype association in patients with WDR35 variants and provides genetic counseling for prevention and intervention in this genetic disorder. Neonatal carriers should be followed up for kidney and CED-related diseases to detect warning signs.

Sections du résumé

BACKGROUND
WDR35 variants are known to cause a rare autosomal recessive disorder-Cranioectodermal dysplasia (CED). The CED patients are commonly present with facial dysmorphisms (frontal bossing and low-set ears), sagittal craniosynostosis, growth retardation, dolichocephaly, skeletal deformities (brachydactyly, terminal hypoplasia of the fingers and narrow thorax), ectodermal abnormalities (sparse hair, and finger/toe nail dysplasia), nephronophthisis, retinal dystrophy and hepatic fibrosis. Diagnosis of CED can be difficult because it presents with high genetic heterogeneity. However, our understanding of the phenotype of CED caused by WDR35 variants could be more explicit, and the correlation between genotype and phenotype needs further improvement.
CASE PRESENTATION
We report a case of the first Chinses patient of CED caused by WDR35 variants, a 3-year-and-3-month-old patient, who was admitted to our hospital with frontal bossing, growth retardation, low set ears, dolichocephaly, sparse hair, and small limbs, abnormal renal function, and moderate anemia. The child showed a novel phenotype of the ectopic testis except for presenting typical CED characteristics, and he was identified with novel compound heterozygous WDR35 variants (c.2590 C > T, p.Gln864* and c.2408_2416del, p.Asn803_Ala805del; NM_001006657). He was given iron succinate and erythropoietin to improve anemia and to inhibit repeated metabolic acidosis and hyperkalemia through acid correction, diuretic, and potassium-lowering treatments. The parents refused to accept renal replacement therapy for their child and were discharged voluntarily.
CONCLUSIONS
This is the first reported case of the WDR35 variants that can lead to CED and ectopic testis, which is also the first Chinese patient associated with WDR35 variants. This study expands our understanding of genotype-phenotype association in patients with WDR35 variants and provides genetic counseling for prevention and intervention in this genetic disorder. Neonatal carriers should be followed up for kidney and CED-related diseases to detect warning signs.

Identifiants

pubmed: 37596520
doi: 10.1186/s12887-023-04110-1
pii: 10.1186/s12887-023-04110-1
pmc: PMC10436638
doi:

Substances chimiques

Cytoskeletal Proteins 0
Intracellular Signaling Peptides and Proteins 0
WDR35 protein, human 0

Types de publication

Review Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

407

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

Références

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Auteurs

Lijie Li (L)

Department of Nephrology and Rheumatology, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.

Cuihua Liu (C)

Department of Nephrology and Rheumatology, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China. lchlch123@126.com.

Ming Tian (M)

Department of Nephrology and Rheumatology, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.

Guangbo Li (G)

Department of Nephrology and Rheumatology, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.

Jitong Li (J)

Department of Nephrology and Rheumatology, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China. ljtsuc@yeah.net.
Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Zhengzhou, 450018, China. ljtsuc@yeah.net.

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