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Bardet−Biedl Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Besides BBS, gene mutations that lead to ciliary dysfunction are also implicated in other ciliopathies. For example, genetic changes involving BBS14 (CEP290) can also cause Joubert syndrome, Leber congenital amaurosis, Meckel syndrome, and Senior−Loken syndrome (Table 25.1). In addition, BBS may overlap clinically to other syndromes with distinct gene defects (e.g., Alström syndrome containing ALMS1 mutations, and Joubert syndrome containing NPHP1 gene mutations) [13].
The gastrointestinal tract
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
In addition to the cystic diseases of the liver and/or kidneys, congenital hepatic fibrosis can also arise in association with Leber congenital amaurosis and juvenile nephronophthisis (the heterogeneous Senior-Løken syndrome), or as part of a spectrum of ciliopathies (cerebellar vermis aplasia, oligophrenia, congenital ataxia, coloboma and hepatic fibrosis [COACH] syndrome, with features overlapping with Joubert syndrome and Meckel syndrome). It is also a feature of congenital disorder of glycosylation (CDG) type 1B.
Renal Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
ARPKD may present antenatally, with abnormal renal ultrasound (including enlarged, echogenic kidneys), or neonatally with nephromegaly, hypertension and/or renal dysfunction. Less severe cases have hypertension and renal dysfunction in infancy whereas, in later childhood, mild renal disease can coexist with liver fibrosis and portal hypertension. ADPKD can present with loin pain, urinary tract infections (UTIs), mild renal dysfunction or hypertension in childhood but is generally clinically silent until adulthood. Some patients with ADPKD are diagnosed in childhood due to incidental findings on abdominal ultrasound or familial requests for ultrasound screening. This can be debated ethically as there are no proven therapies known, although some asymptomatic children could be recruited to clinical trials. There is a rare and severe early onset variety of ADPKD with tuberous sclerosis due to contiguous mutations of PKD1 and TSC2. Nephronophthisis can be combined with extrarenal manifestations, including situs inversus, cardiac malformations, hepatic fibrosis, cerebellar vermis hypoplasia (Joubert syndrome), retinitis pigmentosa (Senior–Loken syndrome) and multiple developmental and neurological abnormalities (Meckel–Gruber syndrome).
Investigation of CEP290 genotype-phenotype correlations in a patient with retinitis pigmentosa, infertility, end-stage renal disease, and a novel mutation
Published in Ophthalmic Genetics, 2020
Madeline Williamson, Elias Traboulsi, Meghan DeBenedictis
Leber congenital amaurosis (LCA; MIM $204000) describes a type of retinal dystrophy that manifests at a very early age as a result of retinal pigment epithelium and rod and cone photoreceptor cell death. It is characterized by congenital nystagmus, photophobia, severe visual impairment, and severely reduced or extinguished responses on electroretinogram. Senior-Loken syndrome includes the LCA phenotype of the retina along with renal disease most commonly presenting as juvenile nephronophthisis that can progress to kidney failure that may eventually require transplantation. Joubert syndrome (JBTS) is an autosomal recessive disorder characterized by a variable combination of central nervous system defects with a distinctive congenital retinal dystrophy, ocular motor abnormalities, respiratory abnormalities in early infancy, and a characteristic molar tooth sign on brain MRI (2,3). Patients may also have ocular coloboma, hepatic fibrosis, and congenital cystic kidney disease (4,5). Meckel-Gruber syndrome is the most severe CEP290-related disease and is nearly always fatal by the neonatal period. Patients have intrauterine growth retardation with systemic abnormalities including cystic kidneys, polydactyly, encephalocele, and liver fibrosis (6).
Senior-Løken syndrome and intracranial hypertension
Published in Ophthalmic Genetics, 2020
Senior-Løken syndrome (SLS) is a rare, autosomal recessive syndrome first described in 1961 (10,11), and characterised by retinal dystrophy and nephronophthisis. Our patient initially presented with a severe rod-cone retinal dystrophy, and shortly after developed renal failure requiring dialysis and a subsequent renal transplant. Genetic confirmation of SLS was made with biallelic mutations in the SDCCAG8 gene. Four and a half years later, she developed intracranial hypertension. Given the presence of other risk factors for IH, the aetiology is likely multifactorial, consequent to the underlying ciliopathy, renal transplantation, medications and/or weight gain.
Copy-number variation of the NPHP1 gene in patients with juvenile Nephronophthisis
Published in Acta Clinica Belgica, 2021
Mayssa Abdelwahed, Ines Maaloul, Valerie Benoit, Pascale Hilbert, Mongia Hachicha, Hassen Kamoun, Leila Keskes-Ammar, Neila Belguith
NPHP1 and NPHP4 are generally involved in the juvenile form [5]. Mutations in NPHP2/inversin and NPHP9/Nek8 have been found in patients with infantile nephronophthisis [8]. Mutations in NPHP3 have been found in patients with adolescent nephronophthisis [7]. On the other hand, mutations in IQCB1/NPHP5 are systematically associated with NPHP or with Senior-Løken syndrome (SLS) [9]. However, mutations in CEP290/NPHP6, RPGRIP1L/NPHP8 are detected in patients with Joubert syndrome and NPHP [10,11].