Say syndrome: A new case with cystic renal dysplasia in discordant monozygotic twins

We report a term female infant born to nonconsanguineous parents who presented with renal failure at birth, hypothyroidism, cholestasis, and progressive cardiac dysfunction. Multigene next-generation sequencing panels for cholestasis, cardiomyopathy, and cystic renal disease did not reveal a unifying diagnosis. Whole exome sequencing revealed compound heterozygous pathogenic variants in ANKS6 (Ankyrin Repeat and Sterile Alpha Motif Domain Containing 6), which encodes a protein that interacts with other proteins of the Inv compartment of cilium ( NEK8, NPHP2/INVS, and NPHP3). ANKS6 has been shown to be important for early renal development and cardiac looping in animal models. Autopsy revealed cystic renal dysplasia and cardiomyocyte hypertrophy, disarray, and focal necrosis. Liver histology revealed cholestasis and centrilobular necrosis, which was likely a result of progressive cardiac failure. This is the first report of compound heterozygous variants in ANKS6 leading to a nephronopthisis-related ciliopathy-like phenotype. We conclude that pathogenic variants in ANKS6 may present early in life with severe renal and cardiac failure, similar to subjects with variants in genes encoding other proteins in the Inv compartment of the cilium.

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Fetal and Postnatal Magnetic Resonance Imaging of Unilateral Cystic Renal Dysplasia in a Neonate with Tuberous Sclerosis

Pediatrics & Neonatology ◽

10.1016/j.pedneo.2013.10.014 ◽

2016 ◽

Vol 57 (5) ◽

pp. 440-443 ◽

Cited By ~ 1

Author(s):

Vineet Tyagi ◽

Eran Bornstein ◽

Robert Schacht ◽

Shailee Lala ◽

Sarah Milla

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Tuberous Sclerosis ◽

Renal Dysplasia ◽

Resonance Imaging ◽

Cystic Renal Dysplasia

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Variation in Major Pulmonary Fissures: Incidence in Fetal Postmortem Examinations and a Review of Significant Extrapulmonary Structural Abnormalities in Sixty Cases

Pediatric and Developmental Pathology ◽

10.1007/s100249900041 ◽

1998 ◽

Vol 1 (4) ◽

pp. 289-294 ◽

Cited By ~ 2

Author(s):

A.W. Bates

Keyword(s):

Pulmonary Hypoplasia ◽

Chromosomal Abnormalities ◽

Renal Dysplasia ◽

Situs Inversus Totalis ◽

Postmortem Examination ◽

Structural Abnormalities ◽

Appropriate For Gestational Age ◽

Cystic Renal Dysplasia ◽

Left Right Asymmetry ◽

Postmortem Examinations

A retrospective study of 1513 fetal postmortem examination reports from 1967 to 1996 yielded 35 cases with anomalous major pulmonary fissures (2.3%), to which a further 25 cases were added from fetal postmortem examinations performed between 1929 and 1966. Of 60 cases with anomalous fissures, 43 had an absent right horizontal fissure and 8 had a supernumerary left horizontal fissure; the remaining 9 showed various patterns in which one lung lacked major fissures. Histological examination in 29 cases did not reveal any additional pulmonary abnormality and pulmonary maturity was appropriate for gestational age. Additional malformations were present in 40 cases and these were frequently multiple, the most common being central nervous system, cardiovascular, and genitourinary system defects; notable heart malformations (10 cases); hydrocephalus (5 cases); and cystic renal dysplasia (4 cases). Chromosomal abnormalities were demonstrated in six cases although this figure does not reflect their prevalence, as many cases predate the availability of karyotyping. In seven cases, including three with polysplenia syndrome and one with situs inversus totalis, there was evidence of an underlying abnormality of left–right asymmetry, and in 13 cases there was documented pulmonary hypoplasia.

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Recurrent Johanson-Blizzard Syndrome in a Triplet Pregnancy Complicated by Urethral Obstruction Sequence: A Clinical, Molecular, and Immunohistochemical Approach

Pediatric and Developmental Pathology ◽

10.2350/11-04-1020-oa.1 ◽

2012 ◽

Vol 15 (1) ◽

pp. 50-57 ◽

Cited By ~ 3

Author(s):

Katharina Schoner ◽

Barbara Fritz ◽

Georg Huelskamp ◽

Frank Louwen ◽

Martin Zenker ◽

...

Keyword(s):

Phenotypic Variability ◽

Later Life ◽

Renal Dysplasia ◽

Urethral Obstruction ◽

Triplet Pregnancy ◽

Gene Testing ◽

Truncating Mutation ◽

Eosinophilic Granulocytes ◽

Gestational Week ◽

Cystic Renal Dysplasia

We report on a triplet pregnancy of consanguineous parents with one fetus being affected by recurrent Johanson-Blizzard syndrome (JBS). At autopsy in the 35th gestational week, the affected triplet presented with an especially severe and lethal manifestation of the disorder as compared to his elder affected brother and to cases in the literature, thus exemplifying great interfamilial and intrafamilial phenotypic variability. Arhinencephaly and cystic renal dysplasia associated with urethral obstruction sequence were features not described previously in the literature. In addition to the lack of exocrine acini as the characteristic feature of JBS, the pancreas revealed a resorptive inflammatory reaction with infiltration by eosinophilic granulocytes that focally dispersed onto islets of Langerhans, thus favoring a progressive destructive rather than primary dysplastic process and possibly explaining the occurrence of diabetes mellitus in later life. JBS maps to chromosome 15q15-q21.1 and is associated with mutations in the UBR1 gene. Testing the fetus and the affected sibling revealed a homozygous truncating mutation in UBR1. The resulting absence of the UBR1 protein was confirmed by Western blot. Immunohistochemical staining using a commercial anti-UBR1 antibody demonstrated staining, presumably artifactual. This finding suggests that, until an appropriately validated antibody has been identified, this modality should not be utilized for diagnosis or confirmation of this disorder.

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