ABSTRACT
OBJECTIVES: To describe 3 children with mutations in a Meckel syndrome gene (MKS3), with features of autosomal recessive polycystic kidney disease (ARPKD), nephronophthisis, and Joubert syndrome (JS). STUDY DESIGN: Biochemical evaluations, magnetic resonance and ultrasound imaging, electroretinograms, IQ testing, and sequence analysis of the PKHD1 and MKS3 genes were performed. Functional consequences of the MKS3 mutations were evaluated by cDNA sequencing and transfection studies with constructs of meckelin, the protein product of MKS3. RESULTS: These 3 children with MKS3 mutations had features typical of ARPKD, that is, enlarged, diffusely microcystic kidneys and early-onset severe hypertension. They also exhibited early-onset chronic anemia, a feature of nephronophthisis, and speech and oculomotor apraxia, suggestive of JS. Magnetic resonance imaging of the brain, originally interpreted as normal, revealed midbrain and cerebellar abnormalities in the spectrum of the "molar tooth sign" that characterizes JS. CONCLUSIONS: These findings expand the phenotypes associated with MKS3 mutations. MKS3-related ciliopathies should be considered in patients with an ARPKD-like phenotype, especially in the presence of speech and oculomotor apraxia. In such patients, careful expert evaluation of the brain images can be beneficial because the brain malformations can be subtle.
Subject(s)
Abnormalities, Multiple/genetics , Ciliary Motility Disorders/genetics , Membrane Proteins/genetics , Mutation , Polycystic Kidney, Autosomal Recessive/genetics , Abnormalities, Multiple/diagnosis , Brain/abnormalities , Brain/pathology , Child , Ciliary Motility Disorders/diagnosis , Female , Humans , Kidney/abnormalities , Kidney/diagnostic imaging , Kidney/pathology , Liver/abnormalities , Liver/pathology , Magnetic Resonance Imaging , Male , Polycystic Kidney, Autosomal Recessive/diagnosis , Siblings , Syndrome , UltrasonographyABSTRACT
OBJECTIVES: To report a high frequency of idiopathic intracranial hypertension (IIH) in patients with cystinosis and to speculate on the relationship between these two disorders. STUDY DESIGN: Retrospective case series and review of the literature regarding risk factors for the development of IIH in cystinosis. RESULTS: Eight patients with cystinosis had documented papilledema, normal neuroimaging of the brain, cerebrospinal fluid (CSF) opening pressure greater than 200 mm of H2O, and normal CSF composition. No common medication, condition, or disease except cystinosis was found in these persons. Six of the patients had received prednisone, growth hormone, cyclosporine, oral contraceptives, vitamin D, or levothyroxine at the time of onset of IIH. Five patients had previous renal transplants. CONCLUSION: No single risk factor for the development of IIH linked IIH to cystinosis in our patients. However, thrombosis susceptibility as a result of renal disease or impaired CSF reabsorption in the arachnoid villi as a result of cystine deposition might lead to the development of IIH in cystinosis.