In a multidisciplinary outpatient clinic for hereditary skin diseases and/or syndromes involving the skin, 7% (30 of 409) of patients were found to have an abnormality involving the X chromosome, a mutation in a gene located on the X chromosome or a clinical diagnosis of an X‐linked monogenetic condition. The collaboration of a dermatologist and a clinical geneticist proves to be very valuable in recognizing and diagnosing these conditions. By combining their specific expertize in counselling an individual patient, X‐linked diagnoses were recognized and could be confirmed by molecular and/or cytogenetic studies in 24 of 30 cases. Mosaicism plays an important role in many X‐linked hereditary skin disorders. From our experience, we extracted clinical clues for specialists working in the field of genetics and/or dermatology for considering X‐linked disorders involving the skin.

The triad of Currarino, also known as Currarino syndrome or complex, is a rare hereditary syndrome involving a bony sacral defect, an anorectal malformation and a presacral mass. Thus far, only 250 cases have been reported, but milder cases may not be recognized, and many cases may not be published. In addition to disorders of the gastrointestinal and urogenital tracts, sensory and motor deficits may be present. Currently, there are no reports of women with the triad of Currarino undergoing cesarean delivery with the use of neuraxial anesthesia. Neuraxial anesthesia in patients with congenital malformations of the spine may be complicated or contraindicated, depending on the level and severity of the anatomic abnormality. We present the case of a pregnant woman at 36 weeks of gestation who underwent uncomplicated neuraxial anesthesia for cesarean delivery. When neuraxial anesthesia is contemplated in such patients, they should first receive careful neurologic and radiologic evaluation.

Oculo‐dento‐digital dysplasia (ODDD, OMIM no.164210) is a pleiotropic disorder caused by mutations in the GJA1 gene that codes for the gap junction protein connexin 43. While the gene is highly expressed in skin, ODDD is usually not associated with skin symptoms. We recently described a family with ODDD and palmoplantar keratoderma. Interestingly, mutation carriers had a novel dinucleotide deletion in the GJA1 gene that resulted in truncation of part of the C‐terminus. We speculated, that truncation of the C‐terminus may be uniquely associated with skin disease in ODDD. Here, we describe a patient with ODDD and palmar hyperkeratosis caused by a novel dinucleotide deletion that truncates most of the connexin 43 C‐terminus. Thus, our findings support the notion that such mutations are associated with the occurrence of skin symptoms in ODDD and provide the first evidence for the existence of a genotype–phenotype correlation. © 2007 Wiley‐Liss, Inc.

Shprintzen-Goldberg syndrome (SGS) is a rare disorder characterized by a Marfan-like habitus, mental retardation and craniosynostosis. Cardiac abnormalities, such as aortic root dilation have also been noted as well as several skeletal abnormalities. Its nosological status is unclear as it is hard to delineate SGS from similar disorders, such as Furlong, Marfan type II, Camurati-Engelmann and Loeys-Dietz syndromes. It has been suggested that these conditions represent a phenotypical spectrum associated with aberrant TGF-beta signalling. In support of this notion, we found a novel TGFBR2 missense mutation in a patient with features of SGS.

BACKGROUND:Conradi-Hünermann-Happle syndrome [X-linked dominant chondrodysplasia punctata type 2 (CDPX2); MIM no. 302960] is an X-linked dominant disorder of cholesterol metabolism that causes a wide spectrum of skeletal abnormalities and linear ichthyosiform skin lesions. Mosaicism is probably responsible for the variability of the phenotype.OBJECTIVES:To describe new mutations in patients with variable manifestations of the disease.METHODS:We studied three patients with CDPX2. We performed mutation analysis of the EBP (formerly known as CDPX2) gene and gas chromatography-mass spectroscopy on serum of two patients.RESULTS:We found two novel (3G-->T and 419-422delTTCT) and one known mutation in the EBP gene. We demonstrated the presence of increased levels of dehydrocholesterol and 8(9)-cholestenol in the two patients with new mutations, confirming the diagnosis of CDPX2 and strongly suggesting that the mutations are indeed pathogenic. One patient had a very mild phenotype, presenting with linear alopecia and a mild symmetrical epiphyseal dysplasia. X-inactivation studies in peripheral blood of all patients showed skewing in only the most severely affected patient.CONCLUSIONS:The strong phenotypic variability in our patients suggests that there is no clear genotype-phenotype correlation.

Prenatal DiagnosisVolume 26, Issue 4 p. 373-376 Letter to the Editor Prenatal diagnosis of bronchial atresia, early in pregnancy L. K. Duin, Corresponding Author L. K. Duin Department of Obstetrics and Gynecology of the University Hospital Maastricht, The NetherlandsDepartment of Obstetrics and Gynecology of the University Hospital Maastricht, The Netherlands.Search for more papers by this authorD. Marcus-Soekarman, D. Marcus-Soekarman Department of Genetics of the University Hospital Maastricht, The NetherlandsSearch for more papers by this authorM. M. L. Baldewijns, M. M. L. Baldewijns Department of Pathology of the University Hospital Maastricht, The NetherlandsSearch for more papers by this authorS. G. F. Robben, S. G. F. Robben Department of Radiology of the University Hospital Maastricht, The NetherlandsSearch for more papers by this authorJ. G. Nijhuis, J. G. Nijhuis Department of Obstetrics and Gynecology of the University Hospital Maastricht, The NetherlandsSearch for more papers by this author L. K. Duin, Corresponding Author L. K. Duin Department of Obstetrics and Gynecology of the University Hospital Maastricht, The NetherlandsDepartment of Obstetrics and Gynecology of the University Hospital Maastricht, The Netherlands.Search for more papers by this authorD. Marcus-Soekarman, D. Marcus-Soekarman Department of Genetics of the University Hospital Maastricht, The NetherlandsSearch for more papers by this authorM. M. L. Baldewijns, M. M. L. Baldewijns Department of Pathology of the University Hospital Maastricht, The NetherlandsSearch for more papers by this authorS. G. F. Robben, S. G. F. Robben Department of Radiology of the University Hospital Maastricht, The NetherlandsSearch for more papers by this authorJ. G. Nijhuis, J. G. Nijhuis Department of Obstetrics and Gynecology of the University Hospital Maastricht, The NetherlandsSearch for more papers by this author First published: 27 March 2006 https://doi.org/10.1002/pd.1395Citations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume26, Issue4April 2006Pages 373-376 RelatedInformation

Birt-Hogg-Dubé (BHD) syndrome is an autosomal-dominantly inherited cancer syndrome characterized by fibrofolliculomas, lung cysts leading to pneumothorax, and chromophobic/oncocytic renal cell carcinoma. The disease is caused by heterozygous mutations in the BHD gene encoding folliculin and all mutations reported putatively lead to protein truncation. Although the function of folliculin is unknown, it is thought to be a tumor suppressor, with loss of heterozygosity (LOH) initiating tumor formation. Here, we report on four novel BHD gene mutations, including two splice-site mutations, in patients presenting with skin lesions only. We further show that LOH cannot be detected in fibrofolliculomas from three patients, suggesting that for the manifestation of cutaneous tumors in BHD syndrome haplo-insufficiency of folliculin is sufficient to initiate uncontrolled growth. Renal microscopic oncocytosis in BHD is considered as a precursor to malignant kidney tumors and may likewise be the result of haplo-insufficiency, with somatic second-hit mutations or LOH giving rise to malignancy later in life.

Background: Chronically compromised uterine perfusion may lead to placental insufficiency and subsequent intrauterine growth restriction (IUGR). Various therapeutic approaches (e.g. vasodilators, low-dose aspirin, intravenous glucose infusion, and hemodilution) are often of limited efficacy. Local anesthetics have been shown to improve placental blood flow in pre-eclamptic women. We hypothesized that epidural administration of local anesthetics might improve outcome in IUGR independent of the underlying cause. In preparation for a clinical trial to test this hypothesis, we performed a pilot study in 10 patients. Methods: After approval of the study protocol, 10 pregnant women presenting with oligohydramnios and IUGR were included in the study. In addition to our standard protocol (magnesium, glucose, betamethasone), each patient received an epidural catheter (T10/T12) with continuous infusion of bupivacaine 0.175% at a rate of 5 ml/h. Uteroplacental circulation was monitored by Doppler sonography and the amount of amniotic fluid was estimated daily. Results: Epidural insertion and infusion was performed without complications. Four patients continued to deteriorate rapidly, amniotic fluid volume did not change and uterine artery pulsatility index (PI) tended to increase. In the remaining 6 patients the clinical status stabilized, amniotic fluid volume tended to increase and uterine artery PI tended to decrease during treatment. This improvement was associated with a prolonged interval to cesarean section and increased infant birth weight. Conclusion: Our data suggest that, even if the underlying cause of IUGR is not pre-eclampsia, epidural local anesthetic administration might improve placental blood flow and be beneficial in a subgroup of patients. A clinical trial to test this hypothesis appears warranted.

The detection of echodense fetal bowel on ultrasound examination in the second trimester of pregnancy justifies invasive procedures such as amniocentesis to detect an underlying cause. We present a case in which initial tests identified only one mutation in the cystic fibrosis transmembrane regulator (CFTR)-gene of the fetus, the family history being negative for CF. Strongly reduced intestinal enzyme activities suggested intestinal obstruction and further increased the estimated risk for CF. After the 24th gestational week, a second mutation was found, confirming cystic fibrosis in this child. Problems in counseling in this particular case are discussed.

Nowadays, improved ultrasound techniques enable the detection of more subtle congenital abnormalities at an earlier stage of fetal development. Current cytogenetic techniques can characterize a chromosomal abnormality in greater detail. These advancements in both diagnostic possibilities have helped to answer many questions but have also created new issues and dilemmas in counselling. This is illustrated by this case report of a 35-year-old woman, who presented at the end of the second trimester of her first pregnancy. Sonographic examination indicated an abnormal external genital in a male fetus. A differential diagnosis of hypospadia was made. During follow-up, an amniocentesis was performed, and this showed a 45,X/46,X,idic(Y)(qter-p11.32::p11.32-qter) karyotype as the cause of the sonographic findings. Cytogenetic characterization of the isodicentric Y chromosome and pre- and post-natal findings in the child are reported. Cases with a similar karyotype reported in the literature are reviewed. Copyright (c) 2005 John Wiley & Sons, Ltd.

We report on monozygotic (MZ) twins with a de novo mos 46,XX,der(15)t(11;15)(p12;p11.2)/46,XX karyotype varying in different tissues. The clinical presentation and findings at the cytogenetic level are described. One of the infants had definite minor anomalies at birth, also found in other cases of trisomy of 11p resembling the Beckwith-Wiedemann syndrome. Theoretical backgrounds regarding the string of events leading to the cytogenetic findings in these twins and the various factors that might have contributed to the dissimilarities in phenotype between these twins are discussed.