A Spanish Family with Gordon Syndrome Due to a Variant in the Acidic Motif of WNK1.

(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.

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes.

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.

Manguito periportal como signo ecográfico de síndrome mieloproliferativo / Periportal cuffing as an ultrasound sign of myeloproliferative syndrome

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Diagnóstico ecográfico de catarata / Ultrasound diagnosis of a cataract

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Tortícolis como forma de presentación de quiste de la bolsa de Blake. Diagnóstico ecográfico en atención primaria / Torticolis as a form of presentation of Blake's pouch cyst. Ultrasound diagnosis in primary care

La tortícolis es un signo clínico definido por la inclinación lateral del cuello y rotación de la cabeza, que puede ser fija o flexible y acompañarse o no de dolor cervical. Aparece en trastornos de diferente complejidad. Ante un caso de tortícolis, es preciso realizar una historia clínica cuidadosa y un examen físico completo, y, en caso de ser persistente, solicitar pruebas de imagen.Se hace referencia a una causa de tortícolis no descrita en la literatura. Se trata de una tumoración quística compresiva en la fosa craneal posterior, quiste de la bolsa de Blake, en una lactante pequeña diagnosticada mediante ecografía en la consulta de Pediatría de Atención Primaria. Tras el diagnóstico, se remitió al centro hospitalario de referencia, donde se intervino de urgencia por Neurocirugía Pediátrica, mediante fenestración de la tumoración por ventriculostomía endoscópica y derivación ventrículo-peritoneal. Actualmente, se encuentra asintomática y sin secuelas.

Torticollis is a clinical sign defined by the lateral inclination of the neck and rotation of the head, which can be fixed or flexible and accompanied or not by cervical pain. It appears in disorders of different complexity. In a case of torticollis it is necessary to carry out a careful medical history and a complete physical examination and, if persistent, request imaging tests.Reference is made to a cause of torticollis not described in the literature. This is a compressive cystic tumor in the posterior cranial fossa, Blake's pouch cyst, in a small infant diagnosed by ultrasound in the Primary Care Pediatrics office. After diagnosis, she was referred to the referral hospital, where emergency intervention was performed by pediatric neurosurgery, by fenestration of the tumor by endoscopic ventriculostomy and ventriculo-peritoneal shunt. She is currently asymptomatic and without sequelae.

[Torticolis as a form of presentation of Blake's pouch cyst. Ultrasound diagnosis in primary care]. / Tortícolis como forma de presentación de quiste de la bolsa de Blake. Diagnóstico ecográfico en atención primaria.

Torticollis is a clinical sign defined by the lateral inclination of the neck and rotation of the head, which can be fixed or flexible and accompanied or not by cervical pain. It appears in disorders of different complexity. In a case of torticollis it is necessary to carry out a careful medical history and a complete physical examination and, if persistent, request imaging tests. Reference is made to a cause of torticollis not described in the literature. This is a compressive cystic tumor in the posterior cranial fossa, Blake's pouch cyst, in a small infant diagnosed by ultrasound in the Primary Care Pediatrics office. After diagnosis, she was referred to the referral hospital, where emergency intervention was performed by pediatric neurosurgery, by fenestration of the tumor by endoscopic ventriculostomy and ventriculo-peritoneal shunt. She is currently asymptomatic and without sequelae.

La tortícolis es un signo clínico definido por la inclinación lateral del cuello y rotación de la cabeza, que puede ser fija o flexible y acompañarse o no de dolor cervical. Aparece en trastornos de diferente complejidad. Ante un caso de tortícolis, es preciso realizar una historia clínica cuidadosa y un examen físico completo, y, en caso de ser persistente, solicitar pruebas de imagen. Se hace referencia a una causa de tortícolis no descrita en la literatura. Se trata de una tumoración quística compresiva en la fosa craneal posterior, quiste de la bolsa de Blake, en una lactante pequeña diagnosticada mediante ecografía en la consulta de Pediatría de Atención Primaria. Tras el diagnóstico, se remitió al centro hospitalario de referencia, donde se intervino de urgencia por Neurocirugía Pediátrica, mediante fenestración de la tumoración por ventriculostomía endoscópica y derivación ventrículo-peritoneal. Actualmente, se encuentra asintomática y sin secuelas.

Co-occurrence of neurofibromatosis type 1 and optic nerve gliomas with autosomal dominant polycystic kidney disease type 2.

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.

Coexistence of autosomal dominant polycystic kidney disease type 1 and hereditary renal hypouricemia type 2: A model of early-onset and fast cyst progression.

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.

Ecografía clínica en la infección del trato urinario / Clinical ultrasound in urinary tract infection

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