An Unusual Presentation of Denys-Drash Syndrome Due to Bigenic Disease

Eneman, Benedicte; Mekahli, Djalila; Audrézet, Marie-Pierre; Lerut, Evelyne; Damme‐Lombaerts, Rita Van; Heuvel, Lambertus van den; Levtchenko, Elena

doi:10.1542/peds.2013-1524

Cited by 6 publications

(3 citation statements)

References 27 publications

(27 reference statements)

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“…He underwent nephrectomy of the left kidney and in the recent evaluation in 2016 his kidney function was normal. Recently, Eneman et al [2014] reported an unusual DDS patient presenting with bilateral renal cortical cysts mimicking polycystic kidney disease (PKD). They identified a de novo heterozygous missense mutation c.1186G>A (p.Asp396Asn) in the WT1 gene and a heterozygous missense variant c.12439A>G (p.Lys4147Glu) in the PKD1 gene.…”

Section: Resultsmentioning

confidence: 99%

WT1 Haploinsufficiency Supports Milder Renal Manifestation in Two Patients with Denys-Drash Syndrome

Guaragna

Andrade²,

Carli³

et al. 2017

Sex Dev

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Denys-Drash syndrome (DDS) is characterized by nephropathy, genital abnormalities, and predisposition to Wilms' tumor. DDS patients usually present heterozygous de novo germline WT1 mutations. The WT1 gene comprises 10 exons encoding the N-terminal transactivation and the C-terminal DNA-binding regions. Two unrelated patients with genital ambiguity and Wilms' tumor were analyzed by sequencing of the WT1 gene, and 3 mutations in exon 1 were identified of which 2 are novel. Patient 1 carried a c.555delC mutation that causes a frameshift and a premature stop codon. Patient 2 carried both c.421A>C and c.424C>T aberrations that lead to the missense p.Lys141Gln and the nonsense p.Lys142* mutation, respectively. As both patients were heterozygous for the mutations, we tested their parents who did not carry any mutation. Therefore, the 3 WT1 mutations occurred de novo in both patients. Heterozygous mutations result in WT1 haploinsufficiency as they impair protein production. They are associated with a milder DDS phenotype as observed in the patients studied here.

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Section: Resultsmentioning

confidence: 99%

WT1 Haploinsufficiency Supports Milder Renal Manifestation in Two Patients with Denys-Drash Syndrome

Guaragna

Andrade²,

Carli³

et al. 2017

Sex Dev

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“…The most frequent syndrome was Denys-Drash syndrome in 70.8% of patients (17/24) in the present study. Denys-Drash syndrome is characterized by nephrotic syndrome owing to diffuse mesangial sclerosis, male pseudohermaphroditism, and predisposition to develop Wilms tumor and gonadoblastoma [14].…”

Section: Discussionmentioning

confidence: 99%

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan

et al. 2020

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Background: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan. Methods: This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS, by means of two survey questionnaires sent by postal mail. Patients aged < 16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease. Results: A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys-Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy. Conclusions: The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices.

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Section: Discussionmentioning

confidence: 99%

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan

Hamasaki

Hamada

Muramatsu

et al. 2020

Preprint

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Background: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan.Methods: This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS by means of two survey questionnaires sent by postal mail. Patients aged <16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease.Results: A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys–Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy.Conclusions: The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices.Trial registration: Not applicable.

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An Unusual Presentation of Denys-Drash Syndrome Due to Bigenic Disease

Cited by 6 publications

References 27 publications

<b><i>WT1 </i></b>Haploinsufficiency Supports Milder Renal Manifestation in Two Patients with Denys-Drash Syndrome

<b><i>WT1 </i></b>Haploinsufficiency Supports Milder Renal Manifestation in Two Patients with Denys-Drash Syndrome

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan

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