Different Seizure Types and Skin Lesions in Oculocerebrorenal Syndrome of Lowe

Erdogan, Fuesun; İsmailoğulları, Sevda; Soyuer, Işın; Ferahbaş, Ayten; Poyrazoğlu, Hakan

doi:10.1177/0883073807301928

Cited by 14 publications

(16 citation statements)

References 12 publications

(14 reference statements)

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“…These resemble eruptive vellus hair cysts [76] but may also originate from mature hair follicles [77]. Won et al reported large epidermal cysts located on the scalp [78].…”

Section: Clinical Manifestations and Managementmentioning

confidence: 99%

The oculocerebrorenal syndrome of Lowe: an update

2016

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The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, intellectual disability, and proximal renal tubular dysfunction. Whereas the ocular manifestations and severe muscular hypotonia are the typical first diagnostic clues apparent at birth, the manifestations of incomplete renal Fanconi syndrome are often recognized only later in life. Other characteristic features are progressive severe growth retardation and behavioral problems, with tantrums. Many patients develop a debilitating arthropathy. Treatment is symptomatic, and the life span rarely exceeds 40 years. The causative oculocerebrorenal syndrome of Lowe gene (OCRL) encodes the inositol polyphosphate 5-phosphatase OCRL-1. OCRL variants have not only been found in classic Lowe syndrome, but also in patients with a predominantly renal phenotype classified as Dent disease type 2 (Dent-2). Recent data indicate that there is a phenotypic continuum between Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for the loss of enzyme function. Extensive research has demonstrated that OCRL-1 is involved in multiple intracellular processes involving endocytic trafficking and actin skeleton dynamics. This explains the multi-organ manifestations of the disease. Still, the mechanisms underlying the wide phenotypic spectrum are poorly understood, and we are far from a causative therapy. In this review, we provide an update on clinical and molecular genetic findings in Lowe syndrome and the cellular and physiological functions of OCRL-1.

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“…These resemble eruptive vellus hair cysts [76] but may also originate from mature hair follicles [77]. Won et al reported large epidermal cysts located on the scalp [78].…”

Section: Clinical Manifestations and Managementmentioning

confidence: 99%

The oculocerebrorenal syndrome of Lowe: an update

2016

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“…These include mental retardation, neonatal hypotonia, stereotypical behaviour and an increased susceptibility to seizures (2). Magnetic resonance imaging (MRI) indicates cystic lesions in the white matter of Lowe syndrome patients, often in the periventricular region (2,34–36). It is interesting to note that OCRL1 is highly expressed in brain, and that only the longer splice variant, isoform a, is present in this tissue, while other tissues express both isoforms a and b (37,38).…”

Section: Introductionmentioning

confidence: 99%

Impaired neural development in a zebrafish model for Lowe syndrome

Ramirez

Pietka

Jones

et al. 2011

Human Molecular Genetics

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Lowe syndrome, which is characterized by defects in the central nervous system, eyes and kidneys, is caused by mutation of the phosphoinositide 5-phosphatase OCRL1. The mechanisms by which loss of OCRL1 leads to the phenotypic manifestations of Lowe syndrome are currently unclear, in part, owing to the lack of an animal model that recapitulates the disease phenotype. Here, we describe a zebrafish model for Lowe syndrome using stable and transient suppression of OCRL1 expression. Deficiency of OCRL1, which is enriched in the brain, leads to neurological defects similar to those reported in Lowe syndrome patients, namely increased susceptibility to heat-induced seizures and cystic brain lesions. In OCRL1-deficient embryos, Akt signalling is reduced and there is both increased apoptosis and reduced proliferation, most strikingly in the neural tissue. Rescue experiments indicate that catalytic activity and binding to the vesicle coat protein clathrin are essential for OCRL1 function in these processes. Our results indicate a novel role for OCRL1 in neural development, and support a model whereby dysregulation of phosphoinositide metabolism and clathrin-mediated membrane traffic leads to the neurological symptoms of Lowe syndrome.

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“…However, there has been comparatively little research regarding the associated skin lesions. To our knowledge, there are only three published reports in the English literature about the skin lesions associated with Lowe syndrome 4,5,13 , and there are none in the Korean literature. Nandedkar et al 4 reported a case of Lowe syndrome with eruptive vellus hair cyst.…”

Section: Discussionmentioning

confidence: 98%

“…Nandedkar et al 4 reported a case of Lowe syndrome with eruptive vellus hair cyst. Erdogan et al 5 reported a case of accompanying trichoepithelioma, and Batirbaygil and Turgut 13 reported a case consisting of multiple eruption cysts in the oral cavity and hematoma formation. Nandedkar et al 4 found that abnormally high level of extracellular lysosomal enzymes, leaving these enzymes free to cause tissue destruction.…”

Section: Discussionmentioning

confidence: 99%