No abstract

Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant disorder with a variable clinical phenotype including synophrys, hypertelorism, thick eyebrows, long eyelashes, wide nasal bridge, long philtrum, hypertrichosis, growth retardation, and intellectual disability. Cornelia de Lange syndrome (CdLS) is a rare disease characterized by synophrys, long eyelashes, limb abnormalities, generalized hirsutism, growth retardation, and intellectual disability. In both WDSTS and CdLS, the malformations are due to transcriptome disturbance caused by defects in the genes encoding the components of chromatin regulation and transcription process. The overlapping features in these two syndromes may complicate the original diagnosis of a patient. Here, we report on a Wiedemann-Steiner patient found to have a de novo pathogenic <i>KMT2A</i> variation who had been clinically suspected as CdLS. We suggest that targeted next-generation sequencing is a feasible tool for the precise diagnosis of patients who have phenotypically and clinically overlapping features of CdLS and WDSTS.

Shprintzen-Goldberg syndrome is a rare syndrome with craniosynostosis of coronal, sagittal or lambdoidal sutures, dolichocephaly, typical craniofacial features, skeletal abnormalities, scoliosis, joint hyperextensibility or contractures, neurological findings and brain malformations. Fifteen months old male patient with hydrocephalus and dysmorphic facial appearance was referred to our clinic for genetical evaluation. In his dysmorphic examination, the findings were dolichocephaly, prominent forehead and glabella, hypertelorism, prominent eyes, proptosis, depressed nasal root, anteverted nostrils, small nose, low-set and posteriorly rotated, dysplastic ears, microretrognathia, short philtrum, fish mouth of mouth, plump cheeks, high and narrow palate, secondary alveolar arch, pectus carinatum. Hands were small and he had arachnodactyly. Toes were thin. He had also hypotonia and umbilical hernia. With these findings, he was clinically diagnosed as Shprintzen-Goldberg syndrome. This is the first reported case of Shprintzen-Goldberg syndrome from Turkey according to literature review. Öz Shprintzen-Goldberg sendromu koronal, sagital ya da lambdoid sütürlerin kraniyosinostozu, dolikosefali, tipik kraniofasiyal özellikler, iskelet anomalileri, skolyoz, eklem hiperekstansibilitesi veya kontraktürleri, nörolojik anomaliler ve beyin anomalileri ile karakterize nadir görülen bir sendromdur. On beş aylık erkek hasta, hidrosefali nedeniyle genetik inceleme amacıyla polikliniğimize yönlendirildi. Hastanın dismorfik muayenesinde, dolikosefali, belirgin alın ve glabella, hipertelorizm, makroftalmik-proptotik görünüm, basık burun kökü, antevert burun delikleri, küçük burun, düşük, geriye yerleşimli ve displastik kulaklar, mikroretrognati, kısa filtrum, balık ağzı görünümü, dolgun yanaklar, yüksek ve dar damak, sekonder alveolar kemer, pektus karinatum mevcuttu. Ayrıca eller küçüktü ve araknodaktili görünümündeydi. Ayak parmakları da inceydi. Olguda hipotoni ve umblikal herni mevcuttu. Hasta mevcut bulgularla değerlendirildiğinde; klinik olarak Shprintzen-Goldberg sendromu tanısı konuldu ve takibe alındı. Literatür taramalarında Türkiye'den bildirilen ilk olgu olduğunun görülmesi ve nadir görülen bir olgu olması nedeniyle sunulmaktadır.

Alstrom Syndrome is an autosomal recessive genetic disorder affecting multiple systems. The characteristic features of this syndrome are obesity, type 2 diabetes mellitus, rod-cone dystrophy, hearing loss. Developmental delay, nistagmus, dilated cardiomyopathy, hypertension, recurrent pulmonary infections, short stature, hepatic and renal failure endocrine abnormalities are other clinical features of this syndrome. Here we report on a case with Alström Syndrome at the age of thirteen. He was referred to medical genetics clinic from endocrinology where he has been watched because of obesity, type 2 diaibetes mellitus and hypogonadism. His parents were first degree relatives. He was also 95% blind and had hearing loss. When we looked up these findings with a clinical diagnosis we thought about Alström Syndrome. It is a rare disease and difficult to make differential diagnosis with other similar syndromes, therefore this case will be a good example of Alstrom Syndrome for the literature.

The cytochrome P450 2D6 (CYP2D6) is a cytochrome P450 enzyme involved in the oxidative biotransformation of the xenobiotics, carcinogens and various clinically important drugs. Patients are evaluated in three sub-groups of extensive (EM), intermediate (IM) and poor metabolizer (PM) phenotypes due to their drug-metabolising ability for the target CYP2D6 gene. Colchicine non-responsive FMF patients were prospectively genotyped for the major CYP2D6 alleles in the current study. Major CYP2D6 alleles of *1, *3, *4, *5, and *6 were genotyped for 30 responsive and 60 non-responsive FMF patients by multiplex PCR-based reverse-hybridization StripAssay and real-time PCR methods. DNA banks isolated from blood-EDTA were retrospectively used in the current patients and results were compared statistically. Increased CYP2D6 *4 and *6 allele frequencies were highly detected in the colchicine non-responsive FMF patients when compared to the responsive group. Results showed the frequencies of major CYP2D6 *1(wild), *3(2637A > delA), *4(G1934A), *5(total gene deletion) and *6(1707T del) alleles in 0.550, 0.042, 0.158, 0.025 and 0.225 for non-responder and 0.880 and 0.120 (CYP2D6*1 and *4) for the responder groups, respectively. Despite small sample size, this study suggests that there is an association between CYP2D6*4 and CYP2D6*6 alleles and drug intoxicants in colchicine non-responder FMF patients.