A Thanatophoric dysplasia, is a severe congenital anomaly which mostly causes stillbirth or death of the affected baby within hours due to respiratory insufficiency. The diagnosis of TD is typically suspected on ultrasound during the second trimester of pregnancy, when severe shortening of the long bones, frontal bossing, flattened vertebrae, and short ribs that result in a narrow thorax and bell-shaped abdomen, can be seen. Here, we present a case with prenatal ultrasonographic findings suggestive of TD, and highlight the patient's postnatal dysmorphic features and typical radiographic findings. The definitive diagnosis of TD type I (TDI) was made postnatally, when molecular genetic analysis revealed the previously described p.R248C mutation in FGFR3. This case is reported due to its relative long life span and the definitive molecular diagnosis that could be made during hospitalization.

Cytogenetically balanced reciprocal translocation with normal phenotype is the most common structural chromosomal rearrangement in human with approximately 1 in 500 and chromosomally unbalanced progenies or offsprings could be the products of these chromosomal rearrangements (4). Reciprocal translocation including two nonhomologous chromosomes will form a quadrivalent configuration in pachytene in meiosis I and will produce 32 types of gametes because of the alternate, adjacent-1, adjacent-2,3:1 or 4:0 segregations with apparently unbalanced chromosome complements while only two of the 32 are balanced (3,4), The frequency of the alternate and adjacent-1 segregations are far a way the others but the option of the 3:1 segregation, ended with interchange trisomy-monosomy and tersiyer trisomy-monosomy, is need to take consideration (3). Here, we present an interchange trisomy 21 case due to a 3:1 segregation derived from balanced maternal 17;21 translocation.The proband was a thirteen months old girl referred to our department because of the suspected trisomy 21. She was the third living child of healthy and nonconsanguineous parents who had six abortions in obstetric history. The proband was born at term by vaginal delivery and no invasive prenatal diagnosis test was performed in utero. Psychomotor development was severely delayed. Her head control developed at 8 months of age and she could sit without support at 12 months of age. At 13 months of age, weight, height, occipitofrontal circumference, and hand were 2250 gr («3 centile), 69 cm (3 centile), 42 cm (After cultivation of the peripheral blood lymphocytes, G-banding was performed and cytogenetic analysis ended with the derivative chromosomes 17 and 21 probably derived from a balanced reciprocal translocation between chromosome 17 and 21, with the two normal chromosomes 21 and one normal chromosome 17. Parental karyotyping showed that the mother was the translocation carrier, and the proband's final karyotype reported as 47,XX,+21,t(17;21)(qll.2;q22.1)mat.The rates of unbalanced gametes could be different according to the nature of the chromosomes involved to the translocation or the length of the translocated segments, in the 3:1 category and a predisposition for 3:1 segregation in oogenesis (3,4). In addition to the interchromosomal effect in a reciprocal translocation affecting the segregation pattern of unrelated chromosomes, especially chromosome 21, our proband had a balance reciprocal translocation between chromosome 17 and the related small acrocentric (chromosome 21) would further exacerbated the situation (5). …

Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that participate in overlapping clinical features with autism spectrum disorders (ASDs). It has been reported that in addition to common mutations or deletions, individuals with chromosomal duplications including either the MECP2 or UBE3A loci show clinical features related to those of MECP2 duplication syndrome, AS, or ASDs. Here we report a 10-year--10-months old male patient having overlapping clinical features of MECP2 duplication syndrome, AS and ASDs. He had mental retardation, lack of speech and developmental delay, and also dysmorphic features such as plagiocephaly, retrognathia, hyperextensible joints in fingers and elbows, broad great toe and three different sizes of cafe au laits. The X-ray revealed compound craniosynostosis and the cranial MRI at 10 years showed delayed myclination. Due to his clinical features, we performed molecular karyotyping and found numerous genomic alterations. Two of these genomic alterations including duplications of chromosome Xq28 and 15qll.2ql3.l1 were found to be compatible with his clinical findings. According to methylation analysis, duplicated UBE3A gene found to be not methylated. The present case study may contribute to a better definition and an improved comprehension of the overlapping pathways of MECP2 and UBE3A.

45,X/46,XY mosaicism is a rare disorder of sexual development and assumably underdiagnosed condition, and it has an incidence as 1.5 per 10.000 newborns (4). This condition is caused from chromosomal missegregation during early embryonic mitosis, through interchromosomal rearrangement or anaphase lag. It occurs as de novo and it could be favored by an abnormal structure of the Y chromosome (6).45,X/46,XY mosaicism can be seen in cases with normal male external genitalia. This phenotype is generally related with bilateral testes and possible higher number of the cell line with 46,XY in the gonads (9). It was reported that, men with the 45,X/46,XY chromosomal composition have a raised risk for germcell neoplasia of the gonads and the cases with genital ambiguity have higher tumor risk (3). There is no clear prediction of tumor risk in cases with 45,X/46,XY who have a normal male appearance but Cools reported the low risk due to normal external masculinisation score and bilaterally descended testes (2).There was no correlation between the percentage of evaluated lymphocytes cells with 45,X and the severity of ambiguous genitalia or final height (4,1,7).We report a 14 years and 9 months old patient with a normal male phenotype also presenting with few of Turner syndrome stigmata. 45,X/46,XY mosaicism was detected. The patient was referred to our clinic by pediatric endocrinology because of unexplained short stature. He had Tumer-like appearance (broad chest with widely spaced nipples, short stature, cubitus valgus, mild nail dysplasia, renal anomaly). The patient's height was 148cm (He had no history of seizures. The patient had mild mental retardation, his school performance was poor. In the physical examination of our case, he had scoliosis, a scar trail over the left clavicle, cervical asymmetry, short neck, round shaped face, broad nasal root and bridge, upslanting palpebral fissures, synophrys, bushy eyebrows, bulbous nose, anteverted nostrils, high arched palate, malar hypoplasia, dental malocclusion, thin lips, cubitus valgus, simian crease in his left hand, mild hypoplastic nails. He had no vision defects and any hearing problems. Pediatric echocardiography examination was normal. According to abdominal ultrasonography extra renal pelvis view in the left kidney, also double collecting system was seen in the right kidney. Pelvic USG was normal. Routine serum and urine biochemical analysis were in the normal range. From his past medical history, he had congenital torticollis and operated on at 9 years of age. At the moment he had cervical asymmetry, mild short neck and scoliosis.He had normal male external genitalia with a normal penis, marked pubic hair (Tanner stage 3) and there were two palpable testis, each with a volume of 8 mL (tanner stage 2) at ultrasound. Total testosterone serum concentration was 80.78 ng/dl and it is in normal range for tanner stage 2. According to scrotal ultrasound both testis were in normal pubertal size and parenchymal echo is homogeneous. Two anechoic cysts were detected at the right epididymal head localization and the large one is 2x3 mm size. Regular monitoring is essential in these anechoic cysts.Laboratory analysis results showed basal levels of FSH, LH, Estradiol, Cortisol, Prolactin, 1,4-androstenedione, DHEAS, TSH, free T4 all within the nonnal range. …

The aim of this study is to review and evaluate our preimplantation genetic screening (PGS) records in terms of their demographic data, indications, cytogenetic results, pregnancy outcomes and discuss these findings in different aspects. PGS was performed in a total of 84 couples (87 cycles) between the period 2005 to 2015. Biopsied blastomeres from embryos on day 3 were fixed and fluorescence in situ hybridization was carried out for chromosomes 13, 16, 18, 21, 22, X and Y depending on the indication. The diagnostic and clinical data were retrospectively evaluated. A total of 450 blastomeres were biopsied. Ninety-eight of them were found to be suitable for transfer. They were transferred to 72 patients in 75 cycles resulting in 23 pregnancies and 20 healthy births. The most common indication was unexplained infertility. The implantation rate was calculated as 23.4% whereas the take-home baby rate was 26.6% per transfer. The highest rate of healthy living births is achieved in patients having low grade maternal mosaic sex chromosomal aneuploidy. All living births achieved by PGS had normal chromosomal structure which we can propose it as an alternative test for couples at risk to select normal embryos to improve the outcomes of assisted reproductive procedures and to avoid the transfer of chromosomally unbalanced and multiple embryos.

Birt-Hogg-Dube syndrome (BHDS) is rare genodermatosis and is characterized by multiple benign skin tumors such as fibrofolliculoma, trichodiscoma and acrochordon. BHDS increases the risk of certain visceral malignancy. The formation of skin tumors is usually the first manifestation of BHDS and is usually seen between ages 20 and 30. The skin tumors gradually grow over the time and increase their numbers (5). We present this case due to its rarity and to point out the importance of regular follow up due to co-existence of visceral malignancies.A 34-year-old man visited the Department of Dermatology for evaluation of long-standing neck and V of neck papules that he had had for 10 years. He had no special medical or family history of the skin lesions, lung disease, and of benign or malignant tumors. Dermatological examination revealed numerous firm, flesh-colored, dome-shaped, papular lesions ranging from 2 to 5 mm in diameter, distributed on the V of neck and neck area (Fig. la,b). Histopathologic examination of specimen registered upper side cervical region showed elliptical fibrovascular proliferation (Fig. 2). Biopsy material was diagnosed by trichodiscoma. Histopathologic examination of specimen registered lower cervical region showed pedunculated, fibrous mass covered with epithelium of varied thickness. A papillary like dermis was composed of loosely arranged collagen fibers and dilated capillaries and lymphatic vessels (Fig. 3). The material was diagnosed by acrochordon. Abdominal ultrasound did not reveal any renal cancer findings. Computerized tomography scan of the chest has demonstrated that pulmonary nodosite and fibrotic changing.Clinical diagnosis of BHDS requires a minimum of 10 skin lesions clinically compatible with FFs and at least one histologically proven fibrofolliculoma. Thus, based on clinical and histological findings, our patient could be diagnosed as BHDS. He is on regular follow-up because renal and colorectal cancer can occur in this syndrome.BHDS syndrome was first described by Bitt et al. in 1977. BHDS is autosomal dominant genodermatosis. The germline mutations of FLCN gene, localizing on 14 exon of the pi 1.2 region of the chromosome 17, causes BHDS syndrome. BHDS is characterized by fibrofolliculoma in the skin, multiple lung cysts, spontaneous pneumothorax, and kidney tumors. Fibrofolliculomas are usually seen around age 20; lung cysts are between ages 20 and 30; and kidney tumors are between ages 40 and 70 (2). In our case, the patient started developing findings by age 24. Fibrofolliculoma, and trichodiscoma are the most important skin findings in BHDS that are usually asymptomatic, single or multiple, skin-colored, and dome-like papules and mostly localizes in the neck, head, neck, and back areas. Some authors postulated that fibrofolliculoma, and trichodiscoma may be different stages of the same disease (4). Similar clinical findings were observed in our case.The other reported skin lesions include mucosal and oral fibromas, fibrous papule, collagenoma, angiofibromas, perivascular fibromas, focal cutaneous mucinosis, lipoma, angiolipoma, and epidermal cyst. Although the skin lesions are benign, the lesions can cause cosmetic and psychological issues (2). …

A new observation of 13q deletion syndrome: severe undescribed features: 13q deletion syndrome is characterized by a wide phenotypic spectrum resulting from a partial deletion-of the long arm of chromosome 13. It consists predominantly of mental and motor retardation, craniofacial dysmorphia, growth retardation, and several congenital malformations. We present a new case with 13q deletion syndrome phenotypically characterized by severe major malformations, some of them still undescribed, consisting of left diaphragmatic hernia, right pulmonary sequestration, hypoplastic left heart syndrome, pancreatic agenesis, polysplenia, and catastrophic central nervous system malformations: semilobar holoprosencephaly, occipital myelomeningocele, partial agenesis of the corpus callosum and agenesis of olfactory bulbs. Fluorescence in situ hybridization technique using the probe LSI D13S319 (13q1l4) SO/ LSI 13q34 SG determined partial monosomy of chromosome 13 in 39/100 cells (mosaicism).

We present a 9 month-old baby girl with de novo pure interstitial duplication 1q. The girl has dysmorphic craniofacial features as well as neuromotor retardation, multiple subcutaneous solid tissue lesions, urogenital anomalies, cardiac defect, liver parenchyma heterogeneity and intracranial anomaly. The case of de novo duplication of 1q32q42 defined by G-banding and Microarray Comparative Genomic Hybridization (Microarray CGH) was presented with its clinical findings.

LETTER TO THE EDITORCraniorachischisis and anencephaly are serious type of Neural tube defects (NTD), are the opening of almost all the neural tube starting from the brain until the lower spine. NTDs occur because of the interaction of many genes and environmental factors (7,11). Schisis association is the presence of one or more togetherness of combination of neural tube defects, oral clefts, omphalocele, and diaphragmatic hernia (4). Thoracoabdominal syndrome (THAS) is a rare multiple congenital malformation syndrome characterized by omphalocele, diaphragmatic hernia, a defect of the lower sternum, and ectopia cordis with congen- ital cardiac anomalies (2,12).A 32-year-old, gravida 3, para 2, woman was referred to genetic counseling at 14 weeks and 4 days of gestation because of multiple congenital malformations in the fetus. The parents involved in this pregnancy were unrelated, and there was no family history of malformations, diseases, or teratogenic medication. The ultrasound scan revealed a single live fetus with crown-rump length (CRL) of 82 mm, femur length of 14 mm and the amniotic fluid was normal. The fetus had craniorachischisis, in which the open cranial defect (anencephaly) is continuous with the completely open spine (craniorachischisis). Also a large omphalocele and ectopia cordis were detected. The omphalocele was including intestines, liver and heart and the pulsation of the ectopic heart could be seen on the liver. After counseling about the fetus, chorionic villus sampling (CVS) and termination of pregnancy was offered. The parents accepted and CVS was done. The pregnancy was subsequently terminated. The result of karyotype analysis was 46, XY. The fetal examination after termination revealed anencephaly, craniorachischisis, small forehead, hypertelorism, proptosis, wide philtrum, webbed neck, diaphragmatic hernia, a defect of the lower sternum and omphalocele containing the intestines, liver and heart (Fig. 1).The findings of patient such as anencephaly, craniorachischisis, diaphragmatic hernia and omphalocele suggests of schisis association. However, the absent of cleft palate/lip in the patient away from the diagnosis of schisis association. Another syndrome of co-occurrence of omphalocele, diaphragmatic hernia and ectopia cordis is THAS. Pentalogy of Cantrell or THAS is a very rare malformation and X-linked dominant inheritance as far known. The characteristic features of THAS were diaphragmatic and ventral hernias, hypoplastic lung, and ectopia cordis with cardiac anomalies (3). The associated defect of omphalocele and ectopia cordis is the major finding of this syndrome. The associated anomaly with THAS, including exencephaly, craniorachischisis, and intact diaphragm have been variously described (14,15). The absence of cardiac anomaly in the patient and unknown genetic etiology of THAS, that diagnosis isn't exactly for THAS.In our case; the anencephaly, craniorachischisis, diaphragmatic hernia, a defect of the lower sternum and omphalocele were detected in the postmortem examination of the fetus. In the literature, the co-occur- rence of omphalocele and NTD has been reported in many cases. The number of patients with the presence of co-occurrence of NTD with mid-line defect of abdomen and thoracic is quite low. Table I shows the previously published cases with neural tube, thoracic and abdominal defect (1,5,6,8,10,13-16). Relating to NTDs within the eleven cases, there were craniorachischisis in five cases, severe spina bifida in three cases, exencephaly in two cases, and anencephaly in a case. Relating to abdominal wall defects defined omphalocele in six cases, and hernia in three cases. Relating to thoracic defects have been reported diaphragmatic hernia in nine cases, ectopia cordis in four cases, and defect of the lower sternum in three cases within eleven cases. We detected an- encephaly, craniorachischisis, diaphragmatic hernia, ectopia cordis and omphalocele similarly to the previously reported cases. …

Infertility is an important health problem which affects aproximately 10-15% of couples and, in 30-50% of these couples, infertility is due to male factor infertility (1). Recently, Hoffher et al. (4) performed a meta-analysis by reviewing previously published reports in the literature to determine the cumulative frequencies of chromosomal abnormalities and chromosome Y microdeletions in infertile males. According to their results, the 47,XXY karyotype, which is associated with both Klinefelter syndrome and its variants, were found to be the most frequent chromosomal abnormalities, with a frequency of 4.9%, followed by autosomal chromosome abnormalities (3.5%) and structural sex chromosomal abnormalities (1.8%). Furthermore, they estimated that the frequency of Y chromosome microdeletions in infertile males was 3.5% (4). To the best of our knowledge, there have been only thirteen cases reported in the literature in which male factor infertility was found in association with a ring Y chromosome, and in only two of these cases was the male factor infertility not associated with loss of AZFa,b,c regions located at Yql 1.2. While one of these two cases had oligoasthenospermia, the other had azoospermia.Here, we describe the second male patient found with azoospermia in conjunction with mosaicism for 45,X karyotype and ring Y chromosome without AZFa,b,and c deletions.A 29-years old man was admitted to our clinic due to male factor infertility. Neither his previous medical nor family history contained any information of relevance to his case. On physical examination, both testes were soft and 12 cc in size. The ductus deferens was palpable and normal in shape, bilaterally, and there wasn't any sign of varicocele on either side. Analysis of the patient's semen was performed on 2 different occasions and revealed complete azoospermia. The patient's hormone profile was found to be as follows: luteinizing hormone levels were 3.580 mIU/ml (1.70-8.60 mIU/ml), the follicle stimulating hormone levels were 2.760 mIU/ml (1.50-12.40 mIU/ml), and total testosterone and free testosterone levels were 2.630 ng/ml (2.808.00ng/ml) and 10.050 pg/mL (8.90-42.50 pg/mL), respectively. As is standard procedure with men found to have azoospermia, the patient was referred to the medical genetic diagnostic laboratory for both chromosomal karyotyping and Y chromosome microdeletion analysis.Conventional cytogenetic analysis of the patient's peripheral blood lymphocytes revealed a ring chromosome Y (Fig. la). C-banding showed that ring chromosome Y was monocentric and did not contain a constitutional heterochromatin region located in the Yql2 band (Fig. lb). Therefore, the breakpoint on the long arm of chromosome Y was thought to be Yqll.2. The karyotype of the father was found to be normal. FISH analysis showed that the SRY located in the Ypl 1.2 and centromeric alfa satellite DNA was intact on ring chromosome Y (Fig. lc-d). Based on the FISH analysis, the patient's final karyotype was designated as: 45,X[ 10]/46,X,dic r(Y)(pll.2.qll.2)[4]/46,X,r(Y) (pll.2.qll.2)[86], ish r(Y)(pll.2qll.2) (SRY+, DYZ3+, DYZ1-). Y chromosome microdeletion analysis showed that the patient did not have any genomic deletions in the AZFa, AZFb and AZFc regions on the long arm of the Y chromosome.There are only six previous reports in the literature of infertile males that had a ring Y chromosome with AZF deletions that had been studied (2, 3, 5, 6) (Table I). As with our case, five of these patients had azoospermia, whereas one case had oligoastenospermia. Five cases had varying degrees of mosaicism for 45,X and 46,X,r(Y) cell lines. …