RESUMO
(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) activity with normal plasma aldosterone (PA) and sometimes failure to thrive. GS is a heterogeneous genetic syndrome, ranging from severe cases in childhood to mild and sometimes asymptomatic cases in mid-adulthood. (2) Methods: We report here a sizeable Spanish family of six patients (four adults and two children) with GS. (3) Results: They carry a novel heterozygous missense variant in exon 7 of WNK1 (p.Glu630Gly). The clinical presentation in the four adults consisted of hypertension (superimposed pre-eclampsia in two cases), hyperkalemia, short stature with low body weight, and isolated hyperkalemia in both children. All patients also presented mild hyperchloremic metabolic acidosis and low PR activity with normal PA levels. Abnormal laboratory findings and hypertension were normalized by dietary salt restriction and low doses of thiazide or indapamide retard. (4) Conclusions: This is the first Spanish family with GS with a novel heterozygous missense variant in WNK1 (p.Glu630Gly) in the region containing the highly conserved acidic motif, which is showing a relatively mild phenotype, and adults diagnosed in mild adulthood. These data support the importance of missense variants in the WNK1 acidic domain in electrolyte balance/metabolism. In addition, findings in this family also suggest that indapamide retard or thiazide may be an adequate long-standing treatment for GS.
Assuntos
Acidose , Hiperpotassemia , Hipertensão , Indapamida , Criança , Adulto , Humanos , Tiazidas , Proteína Quinase 1 Deficiente de Lisina WNK/genéticaRESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic hereditary renal disease, promoting end-stage renal disease (ESRD). Klinefelter syndrome (KS) is a consequence of an extra copy of the X chromosome in males. Main symptoms in KS include hypogonadism, tall stature, azoospermia, and a risk of cardiovascular diseases, among others. Gitelman syndrome (GS) is an autosomal recessive disorder caused by SLC12A3 variants, and is associated with hypokalemia, hypomagnesemia, hypocalciuria, normal or low blood pressure, and salt loss. The three disorders have distinct and well-delineated clinical, biochemical, and genetic findings. We here report a male patient with ADPKD who developed early chronic renal failure leading to ESRD, presenting with an intracranial aneurysm and infertility. NGS identified two de novo PKD1 variants, one known (likely pathogenic), and a previously unreported variant of uncertain significance, together with two SLC12A3 pathogenic variants. In addition, cytogenetic analysis showed a 47, XXY karyotype. We investigated the putative impact of this rare association by analyzing possible clinical, biochemical, and/or genetic interactions and by comparing the evolution of renal size and function in the proband with three age-matched ADPKD (by variants in PKD1) cohorts. We hypothesize that the coexistence of these three genetic disorders may act as modifiers with possible synergistic actions that could lead, in our patient, to a rapid ADPKD progression.
Assuntos
Síndrome de Gitelman , Falência Renal Crônica , Rim Policístico Autossômico Dominante , Insuficiência Renal Crônica , Síndrome de Gitelman/complicações , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Humanos , Rim/patologia , Falência Renal Crônica/genética , Masculino , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/patologia , Membro 3 da Família 12 de Carreador de Soluto/genéticaRESUMO
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and neurofibromatosis type 1 (NF1) are both autosomal dominant disorders with a high rate of novel mutations. However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and NF1 in a single individual have been reported, but the possible implications of this association are unknown. METHODS: We report an ADPKD male belonging to a family of several affected members in three generations associated with NF1 and optic pathway gliomas. The clinical diagnosis of ADPKD and NF1 was performed by several image techniques. RESULTS: Linkage analysis of ADPKD family was consistent to the PKD2 locus by a nonsense mutation, yielding a truncated polycystin-2 by means of next-generation sequencing. The diagnosis of NF1 was confirmed by mutational analysis of this gene showing a 4-bp deletion, resulting in a truncated neurofibromin, as well. The impact of this association was investigated by analyzing putative genetic interactions and by comparing the evolution of renal size and function in the proband with his older brother with ADPKD without NF1 and with ADPKD cohorts. CONCLUSION: Despite the presence of both conditions there was not additive effect of NF1 and PKD2 in terms of the severity of tumor development and/or ADPKD progression.
Assuntos
Neurofibromatose 1/genética , Glioma do Nervo Óptico/genética , Fenótipo , Rim Policístico Autossômico Dominante/genética , Adolescente , Adulto , Códon sem Sentido , Humanos , Masculino , Neurofibromatose 1/complicações , Neurofibromatose 1/patologia , Neurofibromina 1/genética , Glioma do Nervo Óptico/complicações , Glioma do Nervo Óptico/patologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/patologia , Canais de Cátion TRPP/genéticaRESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid-filled cyst development leading to end-stage renal disease. The rate of disease progression in ADPKD exhibits high inter- and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24-year-old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next-generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.
Assuntos
Proteínas Facilitadoras de Transporte de Glucose/genética , Doenças Renais Policísticas/genética , Erros Inatos do Transporte Tubular Renal/genética , Canais de Cátion TRPP/genética , Injúria Renal Aguda/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Adulto , Pré-Escolar , Feminino , Humanos , Mutação/genética , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/patologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/patologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Erros Inatos do Transporte Tubular Renal/complicações , Erros Inatos do Transporte Tubular Renal/diagnóstico , Erros Inatos do Transporte Tubular Renal/patologia , Adulto JovemRESUMO
BACKGROUND: Congenital nephrogenic diabetes insipidus (NDI) is a rare condition characterized by severe polyuria, due to the inability of the kidneys to concentrate urine in response to arginine vasopressin (AVP). In the majority of the cases, the disease shows an X-linked inherited pattern, although an autosomal recessive inheritance was also observed. METHODS: We report a patient with a severe NDI diagnosed during the neonatal period. Because the patient was female without a family history of congenital NDI, her disease was thought to exhibit an autosomal recessive form. RESULTS: A full mutation analysis of AVP receptor 2 (AVPR2; MIM#300538) gene showed no mutations. However, direct Sanger sequencing of the aquaporin 2 (AQP2) revealed an apparently homozygous mutation at nucleotide position NM_000486.5:c.374C>T (p.Thr125Met) in exon 2. Further customized multiplex ligation-dependent probe amplification (MLPA), single-nucleotide polymorphism (SNP) array analysis, and long-range polymerase chain reaction (PCR) followed by Sanger sequencing showed a heterozygous exonic deletion comprising exons 2, 3, and partially 4 of AQP2. CONCLUSION: This is the first case of a compound heterozygote patient with a missense mutation involving NM_000486.5:exon2:c.374C>T (p.Thr125Met) and a gross deletion of at least exons 2, 3, and partially 4 on the AQP2 to present with a severe NDI phenotype.
Assuntos
Aquaporina 2/genética , Diabetes Insípido Nefrogênico/genética , Deleção de Genes , Mutação de Sentido Incorreto , Adulto , Diabetes Insípido Nefrogênico/patologia , Feminino , Heterozigoto , HumanosRESUMO
BACKGROUND: Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent episodes of fever and polyserositis and by the onset of reactive amyloid-associated amyloidosis. Amyloidosis due to familial Mediterranean fever can lead to end-stage renal disease, culminating in kidney transplantation for some patients. In this study, we report the clinical outcome of two brothers with familial Mediterranean fever who were the inadvertent donor and recipient, respectively, of a kidney. Subsequently, they were diagnosed with renal amyloidosis secondary to familial Mediterranean fever and were successfully treated with anakinra and colchicine. CASE PRESENTATION: Two brothers with familial Mediterranean fever and renal amyloidosis were the inadvertent donor and recipient, respectively, of a kidney. The recipient had presented recurrent acute febrile episodes of familial Mediterranean fever, developed nephrotic syndrome secondary to amyloidosis and needed bilateral nephrectomy and chronic dialysis. His elder brother, in apparent good health, donated his left kidney to his brother. Immediately after the kidney transplantation, both the donor and recipient presented massive proteinuria, impaired renal function and elevated serum amyloid A levels. Biopsies of the brothers' kidneys showed amyloidosis. Genetic studies thereafter revealed a homozygous variant for the MEFV gene (NM_000243.2.c.2082G > A; p.M694I) in both brothers. At this point, both the donor and recipient were treated with colchicine and anakinra, resulting in improved renal function, decreased proteinuria, undetectable serum amyloid A levels and stable renal function at 62 months of follow-up and no major adverse effects. CONCLUSIONS: In familial Mediterranean fever, analyses of the MEFV gene should be performed in potential live kidney donors from a direct family member (either between siblings or between parents and children). In addition, genetic studies are required when consanguinity is suspected between members involved in the living transplant. Finally, anakinra could be a safe adjuvant therapy combined with colchicine for patients with familial Mediterranean fever and amyloidosis, including those with successful kidney transplantation.
Assuntos
Amiloidose/etiologia , Febre Familiar do Mediterrâneo/complicações , Nefropatias/etiologia , Transplante de Rim , Adulto , Amiloidose/diagnóstico , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Homozigoto , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Pirina/genéticaRESUMO
BACKGROUND: Renal angiomyolipomas (AML) are usual manifestations of tuberous sclerosis complex (TSC) that may cause aneurism-related haemorrhages and renal impairment. Everolimus has emerged as an alternative to surgery/embolization. We provide further insight into everolimus safety and efficacy for TSC-related AML. METHODS: This was a Spanish expanded access trial including patients aged ≥18 years with TSC-related AML. They received 10 mg everolimus once daily until AML progression, unacceptable toxicity, death/withdrawal, commercialisation for TSC-related AML, or 1 year after first patient enrolment. The primary outcome was dose-limiting safety according to grade 3/4 adverse events, serious adverse events, or adverse events leading to treatment modification. Secondary outcomes included overall safety and efficacy. RESULTS: Nineteen patients were enrolled and received everolimus for a median of 6.6 (5.3-10.9) months. Eleven (57.9 %) remained on 10 mg/day throughout the study and eight (42.1 %) required treatment modifications due to adverse events; none permanently discontinued treatment. Adverse events were overall grade 1/2 and most frequently included aphthous stomatitis/mucosal inflammation, hypercholesterolaemia/hypertriglyceridaemia, urinary tract infection, hypertension, dermatitis acneiform, and insomnia. Four (21.1 %) patients experienced grade 3 adverse events, none was grade 4, and only one (5.3 %) was serious (pneumonia). AML volume was reduced ≥30 % in 11 (57.9 %) patients and ≥50 % in 9 (47.4 %); none progressed. Right and left kidney sizes decreased in 16 and 14 patients, respectively. CONCLUSIONS: These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes. TRIAL REGISTRATION: EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012.
RESUMO
The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate (PIP2P) 5-phosphatase, is responsible for the phenotypic characteristics of the disease. We report a 22-year-old male with a severe form of OCRL syndrome, diagnosed on the basis of congenital cataracts, severe psychomotor and cognitive deficits, and renal tubular dysfunction without Fanconi syndrome. The patient presented low molecular weight proteinuria, nephrocalcinosis, nephrolithiasis, rickets, and growth retardation and developed progressive renal failure. Genetic analysis showed a novel and de novo deletion of exons 10-13 in the OCRL1 gene.
Assuntos
Síndrome Oculocerebrorrenal/genética , Monoéster Fosfórico Hidrolases/genética , Deleção de Sequência , Sequência de Bases , Éxons , Humanos , Masculino , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Gross haematuria is a common manifestation of autosomal dominant polycystic kidney disease (ADPKD). It can be spontaneous or the result of trauma, renal calculi, tumour, or infection. Spontaneous cyst bleeding is important in this particular group of patients, since it can be prolonged by local activation of fibrinolysis by urokinase. The management of haematuria in ADPKD is usually conservative, including bed rest, blood transfusion, correction of blood disorders, and use of vasopressin and erythropoiesis-stimulating agents. In some patients, the management of gross or life-threatening haematuria may require embolisation and/or nephrectomy. Nonetheless, other methods have been tried to avoid prolonged hospitalisation and nephrectomy and preserve kidney function, such as the use of anti-fibrinolytics. Tranexamic acid was recently suggested as a tool to treat gross haematuria in ADPKD in isolated cases. OBJECTIVE: The aim of this study was to evaluate prospectively the response to tranexamic acid in a group of 8 patients with ADPKD and gross haematuria unresponsive to conventional treatment. RESULTS: The massive bleeding stopped within 2 to 5 days in all patients. The haemoglobin level and renal function subsequently stabilised. There were no side effects or thromboembolic events. In this case series, the largest prospective study so far published and the only one including different degrees of renal function, tranexamic acid is confirmed as a promising tool for treating haematuria due to intracystic bleeding in ADPKD. CONCLUSIONS: In summary, tranexamic acid can be used safely in ADPKD patients with chronic renal impairment or preserved renal function to treat severe haematuria poorly responsive to conventional therapy. Tranexamic acid can be administered orally or IV; and dose adjustment for renal impairment is important. Tranexamic acid therapy may preserve renal function in ADPKD directly, by stopping haematuria episodes, or indirectly, by preventing embolisation and/or nephrectomy. The major limitation of this study is the small sample size and the lack of an untreated control group. We suggest a prospective, randomised controlled study to confirm the efficacy of this treatment, its long-term safety, and the optimal dosage. Further larger and multicentre studies are needed to evaluate the cost-benefit ratio and the limits of this therapy in the clinical setting.
Assuntos
Antifibrinolíticos/uso terapêutico , Hematúria/tratamento farmacológico , Hematúria/etiologia , Rim Policístico Autossômico Dominante/complicações , Ácido Tranexâmico/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
We report the case of a 25-year-old woman who presented with abdominal and flank pain with two successive pregnancies and was diagnosed of giant bilateral renal AMLs and pulmonary LAM associated with TSC in the post-partum of her second pregnancy. This case illustrates that in women with TSC rapid growth from renal AMLs and development of LAM may occur with successive pregnancies. It also stresses the potential for preservation of renal function despite successive bilateral renal surgery of giant AMLs. Moreover, the treatment with a low-dose rapamycin may be an option for LAM treatment. Finally, a low-dose rapamycin may be considered as an adjuvant treatment together to kidney-sparing conservative surgery for renal AMLs.
Assuntos
Angiomiolipoma/terapia , Neoplasias Renais/terapia , Linfangioleiomiomatose/terapia , Complicações Neoplásicas na Gravidez/terapia , Sirolimo/uso terapêutico , Adulto , Angiomiolipoma/complicações , Angiomiolipoma/tratamento farmacológico , Angiomiolipoma/cirurgia , Feminino , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/tratamento farmacológico , Linfangioleiomiomatose/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.
Assuntos
Glomerulonefrite Membranosa/complicações , Rim/patologia , Síndrome Nefrótica/complicações , Rim Policístico Autossômico Dominante/complicações , Adulto , Biópsia , Glomerulonefrite Membranosa/terapia , Humanos , Masculino , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Síndrome Nefrótica/terapia , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/terapia , Proteinúria/complicações , Proteinúria/terapiaRESUMO
A 43-year-old woman with autosomal-dominant polycystic kidney disease (ADPKD) received octreotide for 12 months, and this was associated with a 6.3% reduction in liver volume, an 8% reduction in total kidney volume and stabilization of renal function. There was also a reduction of cyst size in fibrocystic disease of breast. These data suggest that the cyst fluid accumulation in different organs from patients with ADPKD is a dynamic process which can be reversed by octreotide. This is the first report of a case of simultaneous reduction in hepatic, renal and breast cystic volume with preservation of renal function in a patient with ADPKD receiving octreotide.
Assuntos
Cisto Mamário/tratamento farmacológico , Cisto Mamário/etiologia , Cistos/tratamento farmacológico , Cistos/etiologia , Doenças Renais Císticas/tratamento farmacológico , Doenças Renais Císticas/etiologia , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Octreotida/uso terapêutico , Rim Policístico Autossômico Dominante/complicações , Adulto , Feminino , HumanosRESUMO
Tuberous sclerosis complex (TSC) is caused by constitutively activated mammalian target of rapamycin (mTOR) resulting in non-malignant tumours of several organs including renal angiomyolipomas (AMLs). AMLs may originate renal failure, hypertension and spontaneous life-threatening bleeding. Recent reports suggest a possible beneficial role of the mTOR inhibitor rapamycin for TSC. However, safety and efficiency of rapamycin in TSC patients as an anti-proliferative agent are still undefined. A 40-year-old man with sporadic TSC and a history of spontaneous bleeding from his left kidney AMLs received low-dose rapamycin for 12 months, and this was associated with a reduction in bilateral kidney AML volume, stabilization and even improvement of renal function. There was also a reduction of facial angiofibromas, improvement of blood pressure control and absence of AML bleeding over this time period. Brain lesion images remained stable, and no significant rapamycin-associated side effects were noted. To the best of our knowledge, this is the first report of a case of reduction in renal AML volume together with preservation of renal function in a patient with TSC receiving low-dose rapamycin. These data suggest that it could be the result of the anti-angiogenic, anti-fibrotic and anti-proliferative effects of rapamycin.
Assuntos
Angiomiolipoma/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/tratamento farmacológico , Adulto , Humanos , Rim/patologia , Rim/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Esclerose Tuberosa/patologia , Esclerose Tuberosa/fisiopatologiaRESUMO
We report for the first time a case of acute kidney injury associated with severe gastric distention after a laparoscopic Nissen-Rossetti fundoplication of the stomach for hiatal hernia. An abdominal compartment syndrome secondary to intra-abdominal hypertension was suspected. Naso-gastric tube decompression resulted in immediate resaturation of the diuresis and progressive recovery of renal function.
Assuntos
Anuria/terapia , Fundoplicatura , Dilatação Gástrica/terapia , Hérnia Hiatal/cirurgia , Intubação Gastrointestinal , Laparoscopia/efeitos adversos , Abdome , Injúria Renal Aguda/etiologia , Idoso , Anuria/etiologia , Síndromes Compartimentais/etiologia , Síndromes Compartimentais/terapia , Descompressão , Feminino , Dilatação Gástrica/etiologia , Hérnia Hiatal/complicações , Humanos , Obesidade/complicaçõesRESUMO
This is the first report of a case of a reduction in kidney volume and preservation of renal function in a patient with autosomal-dominant polycystic kidney disease (ADPKD) receiving rapamycin. A 42-year-old man with ADPKD and a severe persistent bleeding from his solitary left kidney was successfully treated with tranexamic acid (TXA). He also received low-dose rapamycin for 8 months, and this was associated with a 23.5% reduction in kidney volume, improvement and stabilization of renal function, and normalization of haemoglobin levels. When treatment with rapamycin was interrupted, renal function deteriorated within an 8-month period and haemodialysis (HD) became necessary. Kidney volume increased at once, and life-threatening bleeding prompted a nephrectomy 4 months after the onset of HD. These data suggest that the reduction in kidney volume and preservation of renal function with rapamycin could be the result of the antiangiogenic, antiproliferative effects of rapamycin.
RESUMO
This is the first report of a case of sacral radicular cysts in a patient with autosomal dominant polycystic kidney disease (ADPKD). A 46-year-old woman with ADPKD was found to have bilateral sacral radicular cysts discovered incidentally by magnetic resonance imaging (MRI). Cysts arising from arachnoid or spinal meningeal sac should be considered one of the manifestations of a more widespread connective tissue disorder associated with ADPKD.
RESUMO
We report for the first time a family with type 1 ADPKD in which the marriage between affected non-consanguinous individuals resulted in two live-born heterozygous offspring and two fetuses lost in mid-pregnancy. Given a 25% chance for mutant compound heterozygosity in the offspring of this family, our findings suggest that compound heterozygosity of PKD1 mutations in humans may be embryonically lethal.