In the present investigation we used fibroblasts from Smith-Lemli-Opitzsyndrome patients (SLOS) - a metabolic genetic disease affecting the cholesterol biosynthesis pathway - to investigate the consequences of cholesterol deficiency on cell morphology and protein expression.
Smith-Lemli-Opitzsyndrome (SLOS) is an autosomal recessive disorder due to an inborn error of cholesterol metabolism. The syndrome was first described in 1964 by Smith et al. (1) in a report of three patients who had common clinical features which included microcephaly, dysmorphic facies, limb anomalies, genital malformations, glo- bal developmental delay, and others. This
combined estimate may be obtained by weighing estimates 1 and 2 (Est1 and Est2) by the reciprocals of their respective binomial variances (Var1 and Var2): comb. est. = (Est1/Var1 + Est2/Var2)/ (1/Var1+1/Var2). Identical methodology was applied to three different conditions that should be considered in the differential diagnosis of SLOS: alpha-thalassemia/mental retardation syndrome (MIM 141750), Opitz (G/BBB) syndrome (MIM300000), and Aarskog syndrome (MIM 305400) (Grier et al., 1983; Cappa et al., 1987; Fryns et al., 1992; Guion-De-Almeida and Richieri Costa, 1992; Mc Donald et al., 1993; Teebi et al., 1993; Fernandez et al., 1994; Gibbons et al., 1995; Reardon et al., 1995). The estimates thus obtained are shown in Table 2. These values allow the calculation of the probabilities favoring the diagnosis of SLOS in relation to each one of the other three conditions. If no information about a given trait is available, the probability rate (likeli- hood) takes the indifferent value 1. To exemplify the use of the table data, let us suppose that in a given patient sus- pected of having SLOS or Opitzsyndrome, only the first four features shown in the table were searched and that the first three features were present and the last one was absent. In this case, the likelihood favoring the diagnosis of SLOS
Discussion: Although presenting ocular manifestations, there are no papers referring to the Opitzsyndrome in ophthalmological publications. Those which mention strabismus have no proper descriptions of the ocular motility conditions. The present case showed important oculomotor dissociations, but their causes could not be clarified, due to the premature death of the child.
Smith–Lemli–Opitzsyndrome (SLOS) is an autosomal recessive, malformation syndrome due to an inborn error of cholesterol synthe- sis. It is characterized by a large spectrum of morphogenic and con- genital abnormalities including craniofacial, internal organ malforma- tions, limb and skeletal abnormalities, urogenital abnormalities, intra uterine growth retardation (IUGR), behavioral problems and mental retardation. It is caused by mutations in the DHCR7 gene, resulting in a deficiency of the encoded 7-dehydrocholesterol reductase, which catalyzes the last step of cholesterol biosynthesis pathway. SLOS is characterized by low levels of cholesterol and high concentration of its precursor 7-dehydrocholesterol in blood and tissues.
Fig. 1 . Phenotypic features. Patient 1 (a) at diagnosis presented mildly coarse facial features with high forehead, epicanthic folds, low nasal bridge, broad nasal tip, full cheeks, large mouth with full lips and (b) bifid uvula (a feature present in several Smith–Lemli–Opitzsyndrome patients). In addition, anterior thoracic deformities and scoliosis were also recognized. (c) Currently, with 22 years old (yo), the patient’s face is longer and presents high forehead, large nose with bulbous tip, full cheeks and full lips. Patient 2 (d) at young age had a mildly coarse face with high forehead, epicanthic folds, broad nose, full cheeks, full lips, short neck and asymmetry of upper and lower limbs [radiographic evaluations confirmed the asymmetrical shortening of long bones (more severe on the left lower limb) and punctuate calcification of the epiphyseal regions of long bones, patella and tarsal bones]. (e) The same patient as a young adult (20 yo). The dysmorphic facial features have softened over time. Patient 3 presents (f) an extensive, ill-defined, relatively stable, yellowish scaly plaque affecting the left lower limb, more noticeable at the groin and thigh. The left foot presents pseudosyndactyly. The right foot presents discrete linear hyperqueratotic band over the dorsal surface of the third and fifth toes. (g) On the left buttock, there is a persistent erythematous plaque with large desquamation. (h) Other findings: left hand (and left foot) have severely dystrophic nails. Left hand: multiple finger deformity. Right hand: nail pterygium on the first, third and fourth fingers.
abSTRaCT - Nail-Patella Syndrome (OMIN 161200) (Hereditary Onychodysplasia), first reported by Chatelain in 1820, is a rare polymalformative syndrome that affects tissues of both ecto and mesodermal origin. It is an inherited disorder, transmitted as an autosomal dominant trait, having the responsible gene been mapped to 9q34 and further characterized as encoding for a LIM-homeodomain protein that plays a pivotal role in the dorso-ventral patterning of tis- sues of the developing vertebrate limbs. Clinically, NPS classic features include hypoplastic or absent nails and patellae, joint abnormalities, iliac horns, pigmentary anomalies of the irides and nephropathy. Nail anomalies, usually present at birth, are highly evocative – hypoplastic or even absent nails on the first or second fingers and triangular-shaped lunulae – and allow, upon recognition, to prevent a delayed diagnosis and, as such, joint crippling deformities and renal failure that eventually develop, as patients age. The case of a 4 YO Caucasian boy bearing unstable gait, absent patellae, a PDD (Pervasive Developmental Disorder) meeting some Asperger`s Syndrome criteria and fingernail anomalies is repor- ted. In this case it is noteworthy the sharp contrast between the extent of the dermatological findings and the absence or scarcity of both renal and orthopaedic alterations. In fact, not only no renal and hearing alterations were detected but, apart from the bilaterally absent patellae, a 5 th finger clinodactily and a mild iris dyschromia, no further anomalies
Heavy eye syndrome is an association of anisometropia, usually with high myopia, and hypophoria or hypotropia. The more myopic eye is hypotropic. This disorder was called heavy eye syndrome on the basis of the fanciful idea that the larger, more myopic eye is in a relatively low position, as though it were too heavy. Of course, gravity has no discernible role in the causation, which appears to be an abnormally low muscle path of the lateral rectus in the involved eye. It is caused by conversion of lateral rectus muscle function from abduction to infraduction leading to impaired abduction and supraduction.
The purpose of presenting this case is to caution clinicians regarding the possible association of PDS in young myopes with Krukenberg's spindle. Many patients with PDS remain undetected, while those with glaucoma are misdiagnosed as having juvenile onset glaucoma or primary open angle glaucoma. Those patients with Krukenberg's spindle and without elevated IOP are often treated as normal. These patients must be cautioned re- garding possible future consequences of the dis- ease and the hereditary nature of the syndrome. They must be educated about the importance of regular eye checkups and the possible avoidance of vigorous exercise which may cause liberation of pigment and progression of glaucoma. The case also highlights the importance of looking for subtle signs like phacodonesis and iridodonesis which may be due to increased axial length of the eyeball or may be an associated feature of PDS.
The known or suspected inherited ocular problems play a big role in this syndrome by itself, although they can predispose dogs to develop some other breed-related diseases, as seen ahead. They are trichiasis, caruncular trichiasis, distichiasis, ectopic cilia, entropion, excessive nasal fold, decreased corneal sensitivity, corneal dystrophies, prolapse of the nictitating membrane, keratoconjunctivitis sicca, hereditary cataracts and progressive retinal atrophy. Trichiasis is a condition in which normally positioned but abnormally directed hairs irritate the ocular globe, conjunctiva, or both. It can lead to corneal damage when in direct contact with this structure, and the chronic corneal irritation causes not only extra lacrimation, but also pain, blepharospasm and mucopurulent conjunctival discharge. Its location is commonly in the nasal folds, the upper eyelid, or a combination with entropion in the same area (Stades & Woerdt, 2013).
Background. Cogan’s syndrome is a rare clinical entity whose etiopathology is still unknown, and the treatment strategies are not clearly defined. Case. A 23-year-old male presented with symptoms of headache, peripheral facial palsy, persistent right hearing loss and bilateral papillitis. Workup excluded all infectious, granulomatous, neoplastic, and immune causes. The diagnosis of atypical Cogan’s syndrome was established, and the patient was treated with systemic corticosteroids and later on with cyclophosphamide and methotrexate. There were improvement of visual symptoms and stabilisation of left hearing. Conclusion. Cogan’s syndrome is a very rare disease with no specific biological tests for the diagnosis. The diagnostic exams are mostly important to exclude other etiologies. The atypical ocular and audiovestibular manifestations make the diagnosis difficult, delaying the institution of appro- priate therapy which may result in profound bilateral deafness.
ABSTRACT: Piriformis syndrome is a painful musculoskeletal condition resembling sciatica, secondary to sciatic nerve entrapment in piriformis muscle at the greater sciatic notch and responsible for 6%cases of low back pain, also called back pocket sciatica or wallet sciatica, first described in 1928 by Yeoman. It usually occurs due to abnormalities in piriformis muscle such as hypertrophy, inflammation and anatomic variations resulting in irritation and entrapment of sciatic nerve. The diagnosis of piriformis syndrome is made by clinical features, electromyography and nerve conduction velocity, computed tomography, magnetic resonance imaging and bone scan. Management of piriformis syndrome includes nonsurgical and surgical interventions. Non-surgical management includes- nonsteroidal anti-inflammatory drugs, physical therapy, ultrasound, correction of biomechanical abnormality, lifestyle modifications, local anesthetic and/or steroid injection into the piriformis muscle. Surgical management includes-surgical release of piriformis muscle and decompression of the sciatic nerve. Piriformis Syndrome- a review.
Sharma et al. revealed that overlap syndrome had higher association with increased right ventricular mass and right ventricular remodeling compared to COPD alone. In addition, they indicated that the extent of adverse right ventricular remodeling was correlated with nocturnal oxygen desaturation (97). Former studies exhibited that an explicit approach for the interpretation of pulse oximetry tracing could be a reliable strategy for diagnosis or selection of patients who would most benefit from further polysomnographic assessment for sleep-related breathing disturbances (98,100).
The authors report a 49 years old, female patient who have been operated on several times (antrectomy with Billroth II reconstruction, partial gastrectomy with troncular vagotomy and total gastrectomy) in the last 5 years for recurrent ulcer disease. Three months ago, an abdomen ultra sound was done showing multiples images that suggested liver metastasis, which was confirmed by CT and RM. Two months ago, one new abdomen CT specifi- cally to pancreas was done showing an expansive process in pancreas. Serial gastrine was 1532 pg/ml at the time (reference – until 115) and among clinical history and images exams Zollinger-Ellison Syndrome was suggested, a rare disease case.
A 2 -year-old girl presented to us with recurrent infections, hepato splenomegaly, and photophobia. On examination she had blond hair with a metallic sheen. The blood smear showed giant lysosomes in the white blood cells (fi gure) and we diagnosed Chediak-Higashi syndrome, a rare autosomal recessive disease (gene CHS1/LYST at 1q42.1-2). There have been around 200 cases reported, and giant cytoplasmic granules are pathognomonic. Death often occurs before the age of 7 years because of the so-called accelerated phase, with hepatosplenomegaly, lymphadenopathy, and pancyto penia or severe recurrent bacterial infections.
The preferred treatment for neoplasia associated with Sweet’s syndrome is that in progress and may result in complete remission of the syndrome in the case of a solid tumor. However, a cycle of systemic corticosteroid is administered preliminarily. Sys- temic corticosteroids are the reference standard in the treatment of classic Sweet’s syndrome, and prednisone is the most commonly used drug. 7 Nevertheless, there is no specific guideline for the treat-
Abstract: The authors describe a case of Cowden´s syndrome in a female patient with classic cutaneous lesions, plus papillomatous lesions in the gastrointestinal tract and a previous history of thyroid carcinoma. Mucocutaneous lesions occur in 90% of Cowden's syndrome cases and are characterized by facial trichilemmo- mas, oral mucosal papillomas and benign acral keratoses. Sites of extracutaneous involvement include: the thy- roid, gastrointestinal tract, breast and endometrial tissue. There is risk of malignancies in these organs and they need to be monitored with imaging tests. The early diagnosis of the syndrome by a dermatologist through muco- cutaneous lesions enables the investigation and diagnosis of extracutaneous involvement.