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Aplasia Cutis Congenita (ACC), characterized by the focal absence of the skin and skin adnexia resulting from a developmental failure, may occur as part of Adams-Oliver Syndrome (AOS) which can be defined as a congenital inherited disorder, consisting of terminal transverse limb defects and vascular anomalies in addition to ACC. Coexistence of isolated preaxial polydactyly without terminal extremity defect and ACC is extremely rare. Furthermore, ACC and preaxial polydactyly has not been reported previously. Here we report a three-generation family with autosomal dominant aplasia cutis congenita and preaxial polydactyly in the last generation and discuss whether it is a coincidence or not.

13q deletion syndrome is characterized by mental and motor retardation, craniofacial dysmorphic facial appearance and various congenital malformations. In this article, we present a new case with 13q deletion syndrome phenotypically characterized by fish mouth, choanal atresia and severe mental and motor retardation. In order to determine the certain localization of deleted region high resolution multicolor-banding technique was performed and the karyotype determined as 46,XX,del(13)(q32q33.2). To come in future to a genotype-phenotype correlation, it is very important to delineate the deleted region in such cases in detail by cytogenetic/ molecular cytogenetic methods.

A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome: We report a prenatally sonographically diagnosed conotruncal and urogenital anomaly. Postnatally, the patient presented with seizures, hypocalcemia, hypoparathyroidism and thymic aplasia and diagnosed as DiGeorge syndrome. Echocardiography showed malalignment VSD, supravalvular pulmonary stenosis and overriding aorta. Chromosome and FISH studies showed the association of mosaic type trisomy 21 and 22q11.2 microdeletion. The present patient is the second case of mosaic type of Down syndrome associated with 22q11.2 microdeletion. In addition the patient also had clinical and laboratory features of DiGeorge syndrome.

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders affecting approximately 1/3500 individuals in all ethnic groups. It is characterized by cutaneous and plexiform neurofibromas, café-au-lait spots, Lisch nodules, freckling in axillary and inguinal regions, optic gliomas and an increased risk of malignancy. The mutation rate of NF1 is one of the highest known for human disorders: approximately 50% of all affected individuals carry de novo mutations. Detection of disease causing mutations in the NF1 gene allows presymptomatic and prenatal diagnosis, but is complex and time-consuming due to the large size of the gene, the existence of pseudogenes, the lack of clustering of the mutations in a particular region of the gene, and the variability of clinical findings. Because the time for investigations in prenatal diagnosis is restricted, detection of disease-associated NF1 alleles is more rapid and useful especially for familial cases. Therefore, genetic diagnosis of NF1 is frequently performed by linkage analysis. In our laboratory, 37 families were characterized with this method, of which two requested prenatal diagnosis. One fetus was found to be under NF1 risk. However, parents elected to continue pregnancy: the child is now 2.5 years old and has NF1 features. The phenotypic variability and the absence of genotype-phenotype correlation create difficulties in reproductive decisions for NF1 families, underlining the importance of appropriate counseling and detailed discussion of possible outcomes before genetic testing of the fetus.

A severely mentally and motor retarded girl with monosomy 3pter--p25 and trisomy 8q24-qter due to a familial reciprocal translocation t(3;8) (p25;q24): We report a familial translocation t(3;8) in a three generation family that includes a severely retarded 9-year-old girl with intrauterine and postnatal growth retardation, microcephaly, capillary hemangiomas of the forehead and perioral region, synophrys, ptosis, long philtrum, high arched palate, micrognathia, malformed ears, clinodactyly, hypotonia, mental and motor retardation. The pedigree was highly suggestive ofa familial rearrangement. Cytogenetics and fluorescent in situ hybridization (FISH) showed an unbalanced translocation of chromosomes 3p25 and 8q24 of maternal origin, karyotype 46,XX,der(3)t(3;8)(p25q24)mat. Using FISH the breakpoint at 8q24 was located distal of TRPS1, the gene for trichorhinophalangeal syndrome. The balanced translocation was found in the mother, maternal grandmother and prenatally diagnosed brother. Ten individuals (seven miscarriages, niece, two nephews) probably also had an unbalanced translocation. Genetic counseling was given to the family. Because of the hemizygous deletion of the VHL gene at chromosome 3p25.3, the patient is at risk for von Hippel-Lindau (VHL) syndrome, predisposing to retinal, cerebellar, spinal haemangioblastomas, renal cell carcinoma, phaeochromocytoma and pancreatic tumors. Therefore, for early detection and treatment of VHL syndrome, we performed periodic screening beginning at age 5 years. A familial translocation t(3;8) is very rare and there are no previous reports on terminal monosomy 3p (pter-->p25) and terminal trisomy 8q (q24-->qter).

We present a Turkish family and their 6 children, consecutively affected by Ellis-van Creveld (EVC) Syndrome. Four of the affected children died in the postnatal period, and 2 of them had been admitted to the pediatric cardiology department for their cardiologic evaluation. Since they had the features of the EVC Syndrome, linkage analysis was performed with the polymorphic markers, D4S3360-D4S2366, selected from 4p 16 locus. There was complete segregation between the disease and marker allels and the two affected siblings were homozygote for the polymorphic markers, as expected in autosomal recessive inheritance. The diagnosis of EVC Syndrome was confirmed by this molecular analysis. Two cases with EVC were presented in this report. Case 1 had partial abnormal pulmonary venous return and pulmonary stenosis additional to ostium primum atrial septal defect and mitral cleft. Partial abnormal pulmonary venous return and pulmonary stenosis were previously not reported with EVC Syndrome. Postaxial polydactyly phenotype of the Case 2 differs from her brother's. There is bifid 5th metacarpal and unilateral (L) bifid middle and distal phalanges resembling syndactyly.

The co-occurrence of two numerical chromosomal abnormalities in same individual (double aneuploidy) is relatively rare and the clinical presentations are variable depending on the predominating aneuploidy or a combination effect of both. Furthermore, double aneuploidy involving both autosomal and sex chromosomes is seldom described. We describe a male patient with typical clinical features of Down Syndrome and his karyotype revealed 48,XXY,+21. The phenotypic characteristics of this child have been discussed in the light of the published reports on double aneuploidies of XXY and trisomy 21.

Goldenhar syndrome (GS) or oculoauriculovertebral dysplasia (OAVD) is characterized by pre-auricular skin tags, microtia, facial asymmetry, ocular abnormalities and vertebral anomalies of different size and shape. The phenotypical findings of this syndrome are variable due to heterogenous aetiology. For that reason, the physician sometimes faces difficulty when making a definite diagnosis of OAVD. We reviewed the clinical and laboratory findings of 31 patients (15 boys and 16 girls) aged from 1 day to 16 years with the clinical diagnosis of GS. The characteristic features were pre-auricular skin tags (90%), microtia (52%), hemifacial microsomia (77%) and epibulbar dermoids (39%). Vertebral anomalies were noted in 70% of the patients. Cardiac malformations were found in 39% while a genitourinary anomaly was noted in 23% and various central nervous system malformations in 47%. There were 3 pregnancies following an intracytoplasmic sperm injection (ICSI) technique among the 31 patients. Two patients with GS came from the same family. Their relatives had hydrocephaly, myelomeningocele and neural tube defects. It is known that some chromosomal aberrations are seen in GS. We performed chromosome analysis of 29 patients. Among these cases, only one patient with severe mental and motor retardation had a 47,XX,+der(22)t(11,22)(q23; q11 karyotype due to a maternal balanced translocation t(11;22)(q23;q11). This translocation was demonstrated in her sister, brother and maternal uncle. Additionally CATCH 22 analysis in 13 cases with OAVD with a CATCH 22 phenotype revealed no deletion. OAVD patients present with different morphologic features and systemic manifestations. A multidisciplinary approach should be undertaken by departments such as pediatric cardiology, audiology, ophthalmology and plastic surgery when evaluating patients with OAVD. Chromosome analysis should be performed in every patient with Goldenhar syndrome.

The t(4;8)(p16;p23) is the second most common constitutional chromosomal translocation and is caused by an ectopic meiotic recombination between the olfactory receptor gene clusters (ORGC), located on chromosome 4p and 8p. Given that ORGCs are scattered across the genome and make-up about 0.1% of the human genome we reasoned that translocations between 4p16 and other chromosomes might be mediated by ectopic recombination between different ORGC. In 13 patients, we mapped the breakpoints of either a balanced or unbalanced translocation between chromosome 4p16 and different chromosomes. For all four t(4;8) cases, the breakpoints fall within the 4p and 8pter ORGC, confirming that non-allelic homologous recombination (NAHR) between the ORGC is the main mechanism of the t(4;8) formation. For the nine other translocations, the breakpoints on chromosome 4 mapped to different loci, one of them within the ORGC and in two flanking the ORGC. In these three cases, the translocation breakpoint at the reciprocal chromosome did not contain ORGC sequences. We conclude that only the t(4;8) is mediated by NAHR between ORGC.

Thoracoschisis is a very rare congenital anomaly and is usually associated with limb and abdominal wall defects forming part of limb-body wall complex. We here present a case of a 29-week-4-day pregnancy ended with intrauterine demise. Postmortem examination revealed hiatal hernia, thoracoschisis and protrusion of some part of liver from this defect, left forearm agenesis and right arm and right hand agenesis. The findings accompanying thoracoschisis in this presented case exclude any previously reported related syndrome and we believe that this is a new syndrome.

Here we report a 15-year-old girl patient who had severe mental and growth retardation, cleft palate, hemifacial microsomia, skin tags, hypoplasia of the external auditory canal, scoliosis and renal agenesis. Our patient was the fourth child of nonconsanguineous marriage. Peripheral blood chromosomal analysis of the patient revealed 47,XX,+der(22)t(11;22)(q23;q11). The maternal karyotype was reported as 46,XX,t(11;22)(q23;q11). Maternal balanced translocation t(11;22)(q23;q11) causing Goldenhar syndrome with 47,XX,+der(22) has not been reported previously. The presented case clearly indicates that in every case with Goldenhar syndrome, chromosome analysis should be done for the possibility of unbalanced translocations.

The whistling face syndrome (Freeman-Sheldon Syndrome) is a rare disorder characterized by typical face and limb abnormalities. A wide range of clinical findings have been reported. We report unusual skin dimples in a sporadic case with the whistling face syndrome.

Hereditary gingival fibromatosis and sensorineural hearing loss in a 42-year-old man with Jones syndrome: Gingival fibromatosis is a rare disease, which can be seen as an isolated condition or associated with some uncommon syndromes. This case report describes the evaluation and treatment of a 42-year-old male patient with hereditary gingival fibromatosis, sensorineural hearing loss, undescended testis and maxillary odontogenic cyst (Jones Syndrome). Six years follow up of the index patient after the surgery revealed no recurrence of the gingival fibromatosis. This report also describes the anamnestic data of the patient's family that showed progressive deafness and gingival enlargement in three generations.

We report a prenatally diagnosed balanced de novo translocation t(6;7)(p25;q31). Physical examination of the baby born at term revealed only a posterior cleft palate. Laboratory examinations and radiologic investigations were found normal. Two years follow-up of the patient showed her mental and motor development was appropriate with her age. Our report is the first observation on balanced de novo translocation t(6;7)(p25;q31) and cleft palate. Association of this translocation and cleft palate has not been reported previously.

Complex facio-audio-symphalangism syndrome. an autosomal recessive type?: This report describes a new case of facio-audio-symphalangism syndrome in a 32-year-old female patient from a consanguineous family. She had a severely mentally retarded and anophthalmic sister. These associations might be coincidental or demonstrate genetic heterogeneity in this syndrome We note the diagnostic features of the case, discuss the novel association with consanguinity and highlight the possible heterogeneity of the facio-audio-symphalangism syndrome.

Familial intestinal polyatresia (FIPA) is a rare autosomal recessive disorder. In this article we present a new prenatally diagnosed case with FIPA from consanguineous parents with two affected daughters. The fourth pregnancy was diagnosed prenatally with FIPA at 18 weeks sonographically and these findings were confirmed by postmortem examination.