Sotos syndrome

Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (<1%). The main differential diagnoses are Weaver syndrome, Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal period, therapies are mostly symptomatic, including phototherapy in case of jaundice, treatment of the feeding difficulties and gastroesophageal reflux, and detection and treatment of hypoglycemia. General pediatric follow-up is important during the first years of life to allow detection and management of clinical complications such as scoliosis and febrile seizures. An adequate psychological and educational program with speech therapy and motor stimulation plays an important role in the global development of the patients. Final body height is difficult to predict but growth tends to normalize after puberty

Characteristics of Laryngeal Osteosarcoma : A Critical Review

Laryngeal sarcomas constitute an extremely rare entity among head and neck malignancies. Furthermore, most of them are chondrosarcomas, and the osteogenic form remains a true rarity. In general, there is a lack of information on the characteristics of laryngeal osteosarcoma. Thus, we sought to critically review the existing world literature on laryngeal osteosarcoma in order to develop a more accurate clinicopathological profile of this malignancy. Laryngeal osteosarcoma has a predilection for elderly male patients, as 87% were male in the present series and the mean age was 62 years (range 32-80), and without a direct association with tobacco exposure. Osteosarcoma of the larynx is typically a highly malignant neoplasm that metastasizes early, has a propensity for hematogenous spread and also has a marked tendency to recur. Twelve (41%) out of the 29 cases in the present review with follow-up data had metastatic disease. The aspects that distinguish osteosarcoma from its differential diagnostic alternatives are discussed in this review.Peer reviewe

Generation of Evc2/Limbin global and conditional KO mice and its roles during mineralized tissue formation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113740/1/dvg22879.pd

Molecular and clinical analysis of Ellis-van Creveld syndrome in the United Arab Emirates

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplastic condition with clinical manifestations that include short-limbs and ribs, postaxial polydactyly and dysplastic nails and teeth. In about two thirds of patients, mutations in either <it>EVC </it>or <it>EVC2 </it>genes have been found to be the underlying cause.</p> <p>Methods</p> <p>In this paper, we describe the molecular (DNA sequencing) and clinical analysis of six children diagnosed with EvC from four different families from the United Arab Emirates (UAE).</p> <p>Results</p> <p>All the children had the common clinical and radiological features of this syndrome. However, DNA sequence analysis of the genes shown to be involved (<it>EVC </it>and <it>EVC2</it>) revealed a novel splice site mutation (c.2047-1G>T) in intron 13 of <it>EVC2 </it>gene in one family. In addition, we confirm previous mutational analyses that showed a truncating mutation in exon 13 of <it>EVC </it>gene (c.1813C>T; p.Q605X) in the second family and a single nucleotide deletion (c.981delG; p.K327<it>fs</it>) in exon 8 of <it>EVC2 </it>gene in the third family. No mutations in the exons, splice sites or the promoter regions of either gene have been found in the index case of the fourth family who exhibited "EvC-like" features.</p> <p>Conclusions</p> <p>Given the small population size of UAE, our data illustrates further the molecular heterogeneity observed in EvC patients and excludes the possibility of a common founder effect for this condition in the UAE reflecting the current ethnic diversity of the country.</p

Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: Experience of 370 consecutive cases

<p>Abstract</p> <p>Introduction</p> <p>To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) after induction chemotherapy, with or without concomitant chemotherapy.</p> <p>Methods</p> <p>Between August 2003 and March 2007, 370 patients with locoregionally advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62, stage III in 197, and stage IVA/B in 111 patients. All patients except for 36 patients with cervical lymphadenopathy of 4 cm or less in diameter received 2 cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received cisplatin-based concurrent chemotherapy as well.</p> <p>Results</p> <p>With a median follow-up time of 31 months (range 5 to 61 months), the 3-year local control, regional control, metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate analyses revealed that both age (≤ 60 vs. >60) and N-classification are significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95% confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95% confidence interval [CI] 1.235-5.533); And N-classification is the only significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279-3.098). T-classification and concurrent chemotherapy were not significant prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis revealed that concurrent chemotherapy provided no significant benefit to IMRT in locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4 acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity including xerostomia was observed. However, two patients treated with IMRT and neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment related complications.</p> <p>Conclusion</p> <p>IMRT following neoadjuvant chemotherapy produced a superb outcome in terms of local control, regional control, MFS, DFS, and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy is urgently needed for distant control in patients diagnosed with locoregionally advanced NPC.</p

PAPSS2‐related brachyolmia : clinical and radiological phenotype in 18 new cases

Brachyolmia is a skeletal dysplasia characterized by short spine‐short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from different ethnic backgrounds and ages ranging from infancy to 19 years, with the autosomal recessive form, associated with PAPSS2. The main clinical features include disproportionate short stature with short spine associated with variable symptoms of pain, stiffness, and spinal deformity. Eight patients presented prenatally with short femora, whereas later in childhood their short‐spine phenotype emerged. We observed the same pattern of changing skeletal proportion in other patients. The radiological findings included platyspondyly, irregular end plates of the elongated vertebral bodies, narrow disc spaces and short over‐faced pedicles. In the limbs, there was mild shortening of femoral necks and tibiae in some patients, whereas others had minor epiphyseal or metaphyseal changes. In all patients, exome and Sanger sequencing identified homozygous or compound heterozygous PAPSS2 variants, including c.809G>A, common to white European patients. Bi‐parental inheritance was established where possible. Low serum DHEAS, but not overt androgen excess was identified. Our study indicates that autosomal recessive brachyolmia occurs across continents and may be under‐recognized in infancy. This condition should be considered in the differential diagnosis of short femora presenting in the second trimester