Molecular and neurological characterizations of three Saudi families with lipoid proteinosis

<p>Abstract</p> <p>Background</p> <p>Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood. It is caused by homozygous or compound heterozygous mutations in the <it>ECM1 </it>gene. The disease is largely uncharacterized in Arab population and the mutation(s) spectrum in the Arab population is largely unknown. We report the neurologic and neuroradiologic characteristics and <it>ECM1 </it>gene mutations of seven individuals with lipoid proteinosis (LP) from three unrelated consanguineous families.</p> <p>Methods</p> <p>Clinical, neurologic, and neuro-ophthalmologic examinations; skin histopathology; brain CT and MRI; and sequencing of the full<it>ECM1 </it>gene.</p> <p>Results</p> <p>All seven affected individuals had skin scarring and hoarseness from early childhood. The two children in Family 1 had worse skin involvement and worse hoarseness than affected children of Families 2 and 3. Both children in Family 1 were modestly mentally retarded, and one had typical calcifications of the amygdalae on CT scan. Affected individuals in Families 2 and 3 had no grossneurologic, neurodevelopmental, or neuroimaging abnormalities. Skin histopathology was compatible with LP in all three families. Sequencing the full coding region of <it>ECM1 </it>gene revealed two novel mutationsin Family 1 (c.1300-1301delAA) and Family 2 (p.Cys269Tyr) and in Family 3 a previously described 1163 bp deletion starting 34 bp into intron 8.</p> <p>Conclusions</p> <p>These individuals illustrate the neurologic spectrum of LP, including variable mental retardation, personality changes, and mesial temporal calcificationand imply that significant neurologic involvement may be somewhat less common than previously thought. The cause of neurologic abnormalities was not clear from either neuroimaging or from what is known about <it>ECM1 </it>function. The severity of dermatologic abnormalities and hoarseness generally correlated with neurologic abnormalities, with Family 1 being somewhat more affected in all spheres than the other two families. Nevertheless, phenotype-genotype correlation was not obvious, possibly because of difficulty quantifying the neurologic phenotype and because of genetic complexity.</p

Thyroid-Associated Orbitopathy*

Thyroid-associated orbitopathy (TAO) is usually diagnosed clinically. Early presentation of TAO such as ocular irritation, lid puffiness, and mild retraction may be overlooked and misdiagnosed. Careful clinical evaluation, laboratory investigations, and orbital imaging studies are needed for diagnosing early TAO. Knowing the pathogenesis will open the door for obtaining directed and effective treatment for the inflammatory process in TAO. Most patients with mild to moderate active TAO are treated with observation alone as the available treatment modalities effective in controlling the disease have many potential side effects. Severe active TAO, compressive optic neuropathy, and severe exposure keratopathy are the main indications for treatment with immunosuppressant agents, orbital radiotherapy, or orbital decompression. Surgery remains the final rehabilitation in TAO, which should be done during cicatricial (inactive) TAO when reliable and stable results can be obtained

Different Patterns of Orbital Roof Involvement by Cholesterol Granuloma

Two patients presented with cholesterol granuloma (CG), with completely different patterns of orbital roof involvement. One patient had a large intraorbital cystic CG, whereas the other had a very large intraosseous CG of the frontal bone. The presentation of CG with variable orbital roof involvement highlights the importance of being aware of the clinical characteristics and the imaging features of CG