Rubinstein-Taybi syndrome with piebaldism

A young girl is reported suffering from multiple congenital anomalies typical of Rubinstein-Taybi syndrome, in association with cutaneous lesions of piebaldism and occipital poliosis. Clinical characteristics of both entities are described and cutaneous manifestations of Rubinstein-Taybi syndrome are reviewed. To the best of our knowledge, this is the first case reporting such an association.     

Ectopic pregnancy after a laparoscopically-assisted vaginal hysterectomy

PURPOSE/METHODS: Rubinstein-Taybi syndrome is a constellation of clinical findings characterized by mental and motor retardation, broad thumbs and broad first toes, marked growth retardation, microcrania, typical facies, high-arched palate, and cryptorchidism in males. Ocular and adnexal abnormalities are quite common and include antimongoloid slant of the palpebral fissures, epicanthal folds, congenital obstruction of the lacrimal excretory system, ptosis, strabismus, and severe ametropia. Macrocornea, microophthalmos, colobomas of the iris and of the optic nerve head, congenital cataract, and optic nerve atrophy have also been described. Congenital glaucoma is a rare complication. We examined a patient with Rubinstein-Taybi syndrome with bilateral congenital glaucoma. RESULTS/CONCLUSIONS: Examination of this patient revealed bilateral antimongoloid slants of the palpebral fissures, and bilateral congenital glaucoma. Gonioscopic examination revealed the iris to be inserted flatly into the trabecular meshwork. This case emphasizes the importance of detailed, complete ocular examinations in patients with Rubinstein-Taybi syndrome, and also highlights the occurrence of ocular abnormalities rarely associated with this disease.     

Commentary on magnesium deficiency, substance P receptor up-regulation and NO overproduction

The authors described symptoms of Rubinstein-Taybi syndrome and presented a treatment of this disease. It concerned a 1-year-old baby with obstruction of left lacrimal ducts, psychomotor retardation and facial abnormalities.     

General anesthesia for an infant with Rubinstein-Taybi syndrome

A 5-year-old girl with Rubinstein-Taybi syndrome (RTS) was scheduled for ophthalmic surgery under general anesthesia. RTS is a well-defined syndrome with facial abnormalities including a high palate and micrognathia, broad thumbs and big toes, and mental retardation as main clinical features, which may be complicated with repeated respiratory infections, cardiac anomalies, and so on. Anesthesia was uneventfully induced and maintained with the inhalation of oxygen, nitrous oxide and sevoflurane. Special attention was paid to the possibilities of the difficult airway, aspiration pneumonia and cardiovascular dysfunction during anesthesia. No complications were observed throughout the perioperative procedures.     

Cloning and expression of a rat Smad1: regulation by TGFbeta and modulation by the Ras/MEK pathway

A mouse model of Rubinstein-Taybi syndrome (RTS) was generated by an insertional mutation into the cyclic AMP response element-binding protein (CREB)-binding protein (CBP) gene. Heterozygous CBP-deficient mice, which had truncated CBP protein (residues 1-1084) containing the CREB-binding domain (residues 462-661), showed clinical features of RTS, such as growth retardation (100%), retarded osseous maturation (100%), hypoplastic maxilla with narrow palate (100%), cardiac anomalies (15%) and skeletal abnormalities (7%). Truncated CBP is considered to have been acting during development as a dominant-negative inhibitor to lead to the phenotypes of RTS in mice. Our studies with step-through-type passive avoidance tests and with fear conditioning test showed that mice were deficient in long-term memory (LTM). In contrast, short-term memory (STM) appeared to be normal. These results implicate a crucial role for CBP in mammalian LTM. Our CBP +/- mice would be an excellent model for the study of the role of CBP in development and memory storage mechanisms.     

True synovial metaplasia of breast implant capsules: a light and electron microscopic study

High resolution chromosome analysis, molecular cytogenetics, and study of the association between specific chromosome rearrangements and single gene disorders have provided a chromosomal basis to a number of mendelian diseases. Deletions and duplications of small regions, usually less than 3 Mb in size, result in an alteration of normal gene dosage of a number of unrelated genes physically close to each other and are responsible for contiguous gene syndromes. For example, haploinsufficiency is implicated for del 8q24.1 in Langer-Giedion syndrome, del 17p13.3 in Miller-Dieker syndrome, and del 22q11.2 in DiGeorge and Velo-cardiofacial syndromes. Another chromosomal mechanism causing mendelian phenotypes is translocation, which may eventually interrupt a disease gene. It is assumed that translocation breakpoints are running through a relevant gene, hindering the production of the gene product. An example is breakage 16p13.3 associated with Rubinstein-Taybi syndrome. Females with X/autosome translocations have an almost exclusive inactivation of the normal X. Interruption of a disease gene in the translocated X causes the expression of a mendelian phenotype in the presence of an allelic recessive mutation onto the nonrearranged X. Finally, if a human gene shows exclusive expression from a single parental homologue, ie, it is imprinted, deletion of the chromosomal segment containing the active allele results in structural monosomy and functional nullisomy. This situation is illustrated by Prader-Willi and Angelman syndromes. Over seventy human genes have been precisely assigned to chromosomal regions using a cytogenetic approach. Chromosome techniques combined with molecular methods have proved to have powerful and sensitive diagnostic capabilities.     

Viral hemorrhagic fever]

Rett syndrome and Angelman syndrome are neurodevelopmental disorders characterized by severe intellectual disability, microcephaly, speech disturbance, movement disorders with gait and/or truncal ataxia, and occasionally a similar facial appearance. Both conditions can be difficult to diagnose in girls early in their clinical course and can be difficult to distinguish from each other. Genomic imprinting is a known association in Angelman syndrome and previously has been suggested in Rett syndrome. Our aim was to evaluate the methylation status in a cohort of classical patients with Rett syndrome, using a methylation system for chromosome 15q11-13. Methylation analysis of chromosome 15 has not been previously reported in Rett syndrome. Furthermore, we document the clinical features of 31 girls with classical Rett syndrome and confirm the phenotypic similarities between Rett syndrome and Angelman syndrome. The methylation studies in these girls with Rett syndrome were normal. This excludes an imprinting error of the Angelman syndrome critical region on chromosome 15 (15q11-13) as an association with Rett syndrome, and indicates that methylation studies may be useful in distinguishing Rett syndrome from Angelman syndrome in young patients with an overlapping clinical phenotype. A normal methylation pattern, however, does not exclude the diagnosis of Angelman syndrome and clear distinction between the two syndromes will evolve over time.     

Congenital nephrotic syndrome: a novel phenotype of type I carbohydrate-deficient glycoprotein syndrome

Type I carbohydrate-deficient glycoprotein (CDG) syndrome is a genetic multisystem disorder generally without overt renal problems. We report a neonate with neurological abnormalities and congenital nephrotic syndrome of diffuse mesangial sclerosis type. Serum transferrin isoelectric focusing showed the typical abnormalities of type I CDG syndrome. Normal transferrin focusing findings in other patients with similar renal problems excluded the possibility of a secondary biochemical phenomenon. The diagnosis of type I CDG syndrome was confirmed by demonstration of a deficiency of phosphomannomutase. No evidence of pontocerebellar atrophy was found in imaging or at autopsy. We conclude that congenital nephrotic syndrome may occur in type I CDG syndrome, and that this diagnosis should be considered in patients with congenital nephrotic syndrome. Absence of pontocerebellar atrophy does not exclude the diagnosis of type I CDG syndrome.     

Vasitis nodosa

PURPOSE: To report the association of keratoconus and Turner's syndrome in three patients and to review the ophthalmic manifestations of Turner's syndrome. METHODS: Three patients with keratoconus and Turner's syndrome were identified and reported in a retrospective review. RESULTS: These three cases represent the first series of patients with keratoconus and Turner's syndrome. All three patients underwent penetrating keratoplasty with good visual rehabilitation. None of the patients had other ocular features associated with Turner's syndrome. CONCLUSION: Turner's syndrome is commonly associated with ocular problems. In this series we identify an association of keratoconus with Turner's syndrome. Clearly, a careful ocular examination in this condition with attention to ocular features of Turner's syndrome is important.     

The compactness of ribonuclease A and reduced ribonuclease A

This study reports on a patient with Leigh syndrome with a T-to-C mutation at nucleotide 8993 of mitochondrial deoxyribonucleic acid (T8993C). The authors reviewed 10 Leigh syndrome patients, including ours, with T8993C. Compared with 18 reported patients with Leigh syndrome caused by a T-to-G mutation at nucleotide 8993 (T8993G), Leigh syndrome with T8993C was characterized by a significantly higher frequency of ataxia (P < 0.01). None of the reviewed T8993C-associated Leigh syndrome patients had retinitis pigmentosa, which is one of the characteristic findings in Leigh syndrome with T8993G. The milder symptoms of T8993C-Leigh syndrome can be explained by the milder complex V dysfunction; however, the higher frequency of ataxia in T8993C-Leigh syndrome requires more study.     

Pregnancy-associated Sweet's syndrome: world literature review

Sweet's syndrome (acute febrile neutrophilic dermatosis) is a steroid-responsive dermatosis characterized by pyrexia, neutrophilia, and painful erythematous plaques that histologically show a dense dermal infiltrate of neutrophils. Pregnancy-associated Sweet's syndrome is defined as the initial appearance or recurrent episode of Sweet's syndrome in a pregnant woman. Sweet's syndrome occurring during pregnancy has only been described in four women. The clinical characteristics of the women with pregnancy-associated Sweet's syndrome are reviewed and the differential diagnosis of pregnancy-associated dermatoses that clinically mimic Sweet's syndrome are discussed.     

Gitelman's syndrome is genetically distinct from other forms of Bartter's syndrome

In the past the term Bartter's syndrome has been used to describe a spectrum of inherited renal tubular disorders with hypokalemic metabolic alkalosis and overlapping and additional clinical and biochemical features. Pathogenesis remained uncertain until recently Gitelman's syndrome, the hypokalemic-hypomagnesemic variant with hypocalciuria, was linked to the gene encoding the thiazide-sensitive Na-Cl-cotransporter (TSC) located on chromosome 16q. Various mutations in the TSC gene were identified in patients with Gitelman's syndrome. To clarify whether different forms of hypokalemic tubular disorders (HTD) represent variable phenotypes of a common genetic defect, we performed linkage analyses in 17 families with different symptoms of HTD with four highly polymorphic chromosome 16 DNA markers closely linked to the TSC gene. Linkage of Gitelman's syndrome to the TSC locus was confirmed in our families with a maximum two-point Lod score Z = 4.70 (theta = 0.001) for marker locus D16S526. Highly negative LOD scores were obtained at this locus in our families with classic Bartter's syndrome (Z = 9.89, theta = 0.001) and hyperprostaglandin E syndrome (Z = -11.24, theta = 0.001). Our data prove that Gitelman's syndrome is genetically distinct from classic Bartter's syndrome and hyperprostaglandin E syndrome. It remains unknown if classic Bartter's syndrome and hyperprostaglandin E syndrome are caused by a common genetic defect.     

Prenatal and postnatal prevalence of Turner syndrome. A registry-based study

The prevalence of Turner's syndrome in Denmark 1970-1993 was studied and the validity of prenatal diagnosis was assessed. The study was conducted on prenatal and postnatal Turner's syndrome in the Danish Cytogenetic Central Register. All registered Turner's syndrome karyotypes (100 prenatal cases and 215 postnatal cases) at the Danish Cytogenetic Central Register were included. The main outcome measures were prevalence of Turner's syndrome karyotypes among prenatally tested fetuses and Turner's syndrome among liveborn infants. The results showed that among infant girls, prevalence of Turner's syndrome was 32/100,000. Among female fetuses tested by amniocentesis, prevalence of Turner's syndrome karyotypes was 176/100,000 (relative risk of syndrome, 6.74 compared with prevalence among untested pregnancies). Among female fetuses tested by chorion villus sampling, prevalence of syndrome karyotypes was 392/100,000 (relative risk, 16.8). We excluded prenatal tests referred because of results of ultrasound scanning: among fetuses tested by amniocentesis revised relative risk was 5.68, while revised relative risk among fetuses tested by chorion villus sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turner's syndrome, pregnancy was allowed to continue and 24 of the children were live born. Thirteen of the liveborn children were karyotyped postnatally, and the diagnosis of Turner's syndrome had to be revised for eight, seven being normal girls and one boy. This gives a tentative predictive value of amniocentesis in the diagnosis of Turner's syndrome between 21% and 67%. There was no significant relation between mother's age and risk of Turner's syndrome. In conclusion, a discrepancy between prenatal and postnatal prevalence of Turner's syndrome challenges the specificity of prenatal examination in diagnosing Turner's syndrome.     

Adie syndrome as the initial sign of primary Sj?gren syndrome

PURPOSE: To report Adie syndrome as the initial sign of primary Sj?gren syndrome. METHODS: Case report. RESULTS: Adie syndrome was associated with necrotizing gingivitis and xerostomia. Antibodies against Ro (SS-A) were present. Prednisone and antimalarial drugs were ineffective in treating Adie syndrome but improved the necrotizing gingivitis. CONCLUSION: Search for Sj?gren syndrome is mandated in patients with Adie syndrome. The latter condition is likely related to ganglionitis, a mechanism responsible for peripheral nervous system involvement in primary Sj?gren syndrome.     

Age-related decline in female fertility is not due to diminished capacity of the uterus to sustain embryo implantation

Rapp-Hodgkin syndrome and AEC syndrome are two disorders in which ectodermal dysplasia and clefting are associated. Rapp-Hodgkin syndrome is an autosomal dominant condition characterized by cleft lip and palate, peculiar craniofacial features, and ectodermal dysplasia, consisting of abnormalities of teeth, hair, nails and sweating. AEC syndrome manifests the same defects plus ankyloblepharon and a higher frequency of scalp dermatitis. A child affected by ectodermal dysplasia associated with clefting, ankyloblepharon, severe scalp dermatitis, and the characteristic Rapp-Hodgkin facies is reported. The overlap between Rapp-Hodgkin syndrome and AEC syndrome is discussed. Critical review of both disorders suggest that AEC syndrome and Rapp-Hodgkin syndrome represent the same entity.     

Diagnosis of genetic defects by chromosomal analysis

Of 901 karyotypes performed over a period of 4 years, genetic anomalies were detected in 162 cases. Down's syndrome (trisomy 21) was the most common (168.8%) genetic disorder followed by Turner's syndrome, Philadelphia chromosome, Klinefelter's syndrome, Edward's syndrome (trisomy 18) and Patau's syndrome (trisomy 13). All the three trisomies were detected very early in life. Mean age at the time of diagnosis for Turner's syndrome was 13.3 years, allowing a timely hormone replacement therapy to improve secondary sexual characters. Patients with Klinefelter's syndrome were diagnosed late (mean age 23.6 years), which greatly reduced their chances of an effective therapy to improve the clinical and social outcome.     

Munchausen's syndrome and substance abuse

The syndrome of factitious disorders with physical symptoms was named "Munchausen's syndrome" by Richard Asher (1951). The present article contains an interesting case report of a patient who has a history of Munchausen's syndrome, substance abuse, and genuine physical illness. A review of the literature supports a strong association of substance abuse in patients with Munchausen's syndrome. Also important for clinicians to remember is that patients with Munchausen's syndrome often have true physical illnesses which need appropriate treatment. The patient described here has successfully begun treatment with methadone maintenance, but further study will be needed regarding methadone maintenance's role in the management of Munchausen's syndrome.     

Combining beta-core fragment and total oestriol measurements to test for Down syndrome pregnancies

Recent articles by Cuckle et al., Canick et al., and Isozaki et al. have evaluated urine beta-core fragment as a screening test for Down syndrome in second-trimester pregnancies. They found over four-fold elevation of beta-core fragment levels in Down syndrome pregnancies, and between 62 and 88 per cent detection of this trisomy at a 5 per cent false-positive rate. Urine beta-core fragment may be a superior screening test for Down syndrome pregnancies. In the present study, urinary total oestriol has been evaluated as a marker to use in combination with beta-core fragment in screening for Down syndrome pregnancies. The two markers were evaluated separately in relation to the urine creatinine concentration. To amplify screening performance, we evaluated the ratio of beta-core fragment to total oestriol levels (creatinine-independent). beta-core fragment and total oestriol levels were determined (normalized to creatinine, ng/mg creatinine) in urine samples from 480 unaffected and 12 Down syndrome pregnancies, collected consecutively at a single prenatal diagnosis centre. The median beta-core fragment level in Down syndrome cases was 4.5 MOM. Fifty-eight per cent of Down syndrome cases had beta-core fragment levels exceeding the 95th centile of unaffected pregnancies. The median total oestriol level in Down syndrome cases was 0.33 MOM. Forty-two per cent of Down syndrome cases had total oestriol levels exceeding the 95th centile of unaffected pregnancies. We investigated the ratio of the two determinants (beta-core fragment, ng/ml divided by total oestriol, ng/ml) in our sample set. The median beta-core fragment:total oestriol ratio in Down syndrome cases was 13 MOM. Seventy-five per cent of Down syndrome cases had a ratio exceeding the 95th and the 99.5th centile of unaffected pregnancies. Total oestriol complements beta-core fragment in urine screening for Down syndrome pregnancies. A test measuring the ratio of the two urine determinants may be a significant improvement over current serum methods for detecting Down syndrome.