nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное общество10.28996/2618-9801-2024-2-216-228nid-171Research ArticleНАБЛЮДЕНИЯ ИЗ ПРАКТИКИCASE REPORTSНефронофтиз-ассоциированная цилиопатия в рамках cиндрома Сенсенбреннера: клиническое наблюдение и обзор литературыNephronophthisis-associated ciliopathy within Sensenbrenner's syndrome: clinical report and literature reviewhttps://orcid.org/0000-0001-6459-2795ПапижС. В.PapizhS. V.papijsveta@mail.ruhttps://orcid.org/0009-0001-3993-8472ТопчийА. В.TopchiyA. V.anastasia_topchiy@mail.ruhttps://orcid.org/0000-0002-2672-6294МарковаТ. В.MarkovaT. V.markova@med-gen.ruhttps://orcid.org/0000-0003-4527-4518НагорноваТ. С.NagornovaT. S.t.korotkaya90@gmail.comФГАОУ ВО «Российский Национальный Исследовательский Медицинский Университет им. Н.И. Пирогова» МЗ РФРоссияPirogov Russian National Research Medical UniversityRussian FederationФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian Federation202402072024262216228Copyright © Папиж С.В., Топчий А.В., Маркова Т.В., Нагорнова Т.С., 20242024Папиж С.В., Топчий А.В., Маркова Т.В., Нагорнова Т.С.Papizh S.V., Topchiy A.V., Markova T.V., Nagornova T.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/171

Синдром Сенсенбреннера, также известный как краниоэктодермальная дисплазия, представляет собой ультраредкую аутосомно-рецессивную цилиопатию, вызванную патогенными вариантами в одном из шести генов, включая IFT43, IFT52, IFT122, IFT140, WDR19 и WDR35, кодирующих белки, которые являются частью внутрижгутикового транспортного комплекса A, участвующего в ретроградном цилиарном транспорте. Синдром Сенсенбреннера характеризуется множественными аномалиями с характерными черепно-лицевыми проявлениями (выпуклость лба, долихоцефалия), метафизарной дисплазией (укорочение конечностей, узкая грудная клетка), эктодермальными (редкие волосы, маленькие и отсутствующие зубы, аномальные ногти) и соединительнотканными (гиперэластичная кожа, гипермобильность суставов) аномалиями, дистрофией сетчатки, патологией почек и печени. Мы представляем клиническое наблюдение за мальчиком 5-ти лет с диагнозом синдром Сенсенбреннера с типичными черепно-лицевыми, скелетными и эктодермальными аномалиями в сочетании с патологией почек и прогрессирующим снижением функции почек. Мальчик является вторым ребенком от здоровых родителей, состоящих в неродственном браке. Его масса-ростовые показатели при рождении были в норме (масса 3100 гр. - 50‰, длина 51 см - 50‰). Клиническое обследование, проведенное непосредственно после рождения, выявило черепно-лицевые и скелетные аномалии (долихоцефалия, широкий лоб, эпикант, телекант, узкая грудная клетка, короткие конечности, брахидактилия, синдактилия 2-3 пальцев обеих стоп). По результатам УЗ-исследования при рождении почки были нормального размера без паренхиматозных изменений. В 14 месяцев мальчику была проведена хирургическая коррекция скафоцефалии. В возрасте 2 лет у ребенка наблюдалась задержка физического развития. УЗИ почек выявило двусторонние паренхиматозные кисты (менее 1 см). При первичном обследовании в возрасте 4 лет у мальчика отмечались низкорослость, поясничный сколиоз, метаболический ацидоз, протеинурия до 1,0 г/л с повышенным уровнем β-2-микроглобулина в моче и микроальбуминурия, снижение экскреции кальция, повышение фракционной экскреции калия, натрия и магния. рСКФ была снижена до 54,7 мл/мин/1,73 м2. При УЗИ почек сохранялись кистозные образования (ПП 1,3×1,6 см, ЛП 0,8×0,6 см) и впервые выявлены единичные медуллярные кальцинаты в обеих почках. Для коррекции метаболического ацидоза пациенту был назначен гидрокарбонат натрия. С антипротеинурической и нефропротективной целью было начато лечение ингибиторами АПФ (иАПФ) (эналаприл, 0,125 мг/кг/сут). Методом массового параллельного секвенирования выявлен вариант с неясной клинической значимостью с.2907G>T (p.Lys969Asn) в 25 экзоне гена WDR35 в гомозиготном состоянии. Оба родителя оказались гетерозиготными носителями этого варианта WDR35. 12-месячная терапия гидрокарбонатом натрия способствовала нормализации кислотно-основного состояния, лечение иАПФ привело к уменьшению протеинурии и микроальбуминурии и стабилизации фильтрационной функции почек (рСКФ 50,1 мл/мин/1,73 м2).

Sensenbrenner syndrome, also known as cranio-ectodermal dysplasia, is an ultrarare autosomal recessive ciliopathy caused by pathogenic variants in one of six genes including IFT43, IFT52, IFT122, IFT140, WDR19, and WDR35, all encoding proteins that are part of the intraflagellar transport complex A which is involved in retrograde ciliary transport. Sensenbrenner syndrome is a multiple anomaly syndrome with distinctive craniofacial findings (forehead bossing, dolichocephaly), metaphyseal dysplasia (short limbs, small thorax), ectodermal anomalies (sparse hair, small and missing teeth, short nails), connective tissue abnormalities (loose skin, joint laxity), retinal dystrophy, and chronic kidney and liver disease. In this article, we present a 5-year-old male patient diagnosed with Sensenbrenner syndrome as a typical craniofacial and skeletal anomaly with kidney disease and progressive decline in kidney function. The boy is the second child of healthy non-consanguineous parents. His birth weight was 3390 g (50‰) and the birth length was 51 cm (50‰). Clinical examination performed directly after birth, revealed craniofacial and skeletal abnormalities (dolichocephaly, wide forehead, epicanthic folds, telecanthus, narrow thorax, short limbs, brachydactyly, syndactyly of 2-3 toes of both feet). Postnatal kidney ultrasound (US) showed normal-sized kidneys without parenchymal changes. At the age of 14 months, the boy underwent a surgical correction for scaphocephaly. At the age of 2 years the child presented with failure to thrive, US revealed bilateral solitary parenchymal cysts (<1 cm) in both kidneys. At the first admission at the age of 4 years, the boy had short stature, lumbar scoliosis, metabolic acidosis, proteinuria up to 1.0 g/l with elevated urinary β-2 microglobulin level and microalbuminuria, decreased calcium excretion, increased fractional excretion of potassium, sodium, and magnesium. His eGFR was decreased to 54.7 ml/min/1.73 m2. Kidney US revealed a few cysts (RK 1.3×1.6 cm, LK 0.8×0.6 cm) and single medullary calcifications in both kidneys. Oral sodium hydrocarbonate was given to the patient to correct metabolic acidosis. Treatment with ACE inhibitor (iACE) (enalapril, 0.125 mg/kg/d) was started for antiproteinuric and nephroprotective purposes. NGS identified a variant of uncertain significance с.2907G>T (p.Lys969Asn) in exon 25 of the WDR35 gene in a homozygous state. Both parents were found to be heterozygous carriers of this WDR35 variant. 12-month therapy with sodium bicarbonate led to normalization of the acid-base state, and treatment with iACE led to decreasing proteinuria, microalbuminuria, and stabilization of his kidney function (eGFR 50.1 ml/min/1.73 m2).

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The authors declare that there are no conflicts of interest present.