A case of TRAP sequence: acardiac twin

Monochorionic twinning contributes significantly to neonatal morbidity and mortality. The twin-twin transfusion syndrome complicates 5-35% of monozygotic twin pregnancies with monochorionic placentation. The most severe and a rare manifestation of this condition is acardiac twinning which is seen in 1 in 35,000 pregnancies. The acronym TRAP (Twin Reversed Arterial Perfusion) sequence is used to describe this condition. The acardiac twin does not survive while the mortality for the normal twin is about 50%. Proper timing of the delivery is of prime importance to survival of the normal fetus for which emphasis is placed on close sonographic monitoring for early antenatal diagnosis. We present such a case of TRAP sequence because of its rarity.     

Natural history of Christianson syndrome

Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types. Gilfillan et al.2008] reported mutations in SLC9A6, the gene encoding the sodium/hydrogen exchanger NHE6, in the family first reported and in three others. They also noted the clinical similarities to Angelman syndrome and found cerebellar atrophy on MRI and elevated glutamate/glutamine in the basal ganglia on MRS. Here we report on nonsense mutations in two additional families. The natural history is detailed in childhood and adult life, the similarities to Angelman syndrome confirmed, and the MRI/MRS findings documented in three affected boys.     

Natural history of propionic acidemia

Propionic acidemia is an organic acidemia that can lead to metabolic acidosis, coma and death, if not treated appropriately in the acute setting. Recent advancements in treatment have allowed patients with propionic acidemia to live beyond the neonatal period and acute presentation. The natural history of the disease is just beginning to be elucidated as individuals reach older ages. Recent studies have identified the genomic mutations in the genes PCCA and PCCB. However, as of yet no clear genotype-phenotype correlations are known. As patients age, the natural progression of propionic acidemia illuminates intellectual difficulties, increased risk for neurological complications, including stroke-like episodes, cardiac complications, and gastrointestinal difficulties, as well as a number of other complications. This article reviews the available literature for the natural history of propionic acidemia.     

Natural history study of pseudoachondroplasia

Pseudoachondroplasia (PSACH) is a well-characterized autosomal dominant dwarfing condition. A great deal of information is available about orthopedic complications, but little is known about extraskeletal complications in adulthood. This study was undertaken to delineate the natural history of PSACH at all ages. Seventy-nine individuals responded to an extensive questionnaire that included information about deformities, operations, general health, chronic diseases, and reproduction. PSACH individuals were ascertained through the University of Texas Medical Genetics patient population, a genetic linkage study, and the social organization, Little People of America. The results show that PSACH individuals with a family history do not have a distinct or more severe phenotype than new mutation cases. There were no differences in the number of orthopedic complications, operations, or number of offspring between these two groups. Less than half of affected adults reported having total hip replacement surgery, which was less common than previously reported. Extraskeletal complications were generally uncommon. There were four cases of cancers in 41 individuals queried. Premature osteoarthritis was the major health problem for PSACH individuals. PSACH individuals are generally healthy but have problems associated with debilitating osteoarthritis. © 1996 Wiley-Liss, Inc.     

Natural history of Danon disease

BackgroundDanon disease is a rare but serious cardiac and skeletal myopathy leading to substantial morbidity and early mortality due to arrhythmia and cardiomyopathy. The X-linked nature of inheritance accounts for reported differences in phenotypic severity between men and women. The rarity of Danon disease has limited understanding of the complete phenotype. Clinical estimates of ages of disease onset and survival based on gender have not been published.Methods and ResultsWe present data on 82 patients with Danon disease from 36 families, the largest series to date. Men were severely affected with cognitive disabilities (100%), hypertrophic cardiomyopathy (88%), and muscle weakness (80%). Men had a high morbidity and were unlikely to reach the age of 25 years without a cardiac transplantation. Women were less severely affected but reported higher than expected levels of cognitive (47%) and skeletal muscle complaints (50%) and manifesting an equal prevalence of dilated cardiomyopathy and hypertrophic cardiomyopathy. Combining our data with that of 63 other Danon disease case reports in the literature, the average ages of first symptom, cardiac transplantation, and death were 12.1, 17.9, and 19.0 years in men and 27.9, 33.7, and 34.6 years in women, respectively.ConclusionThese data more broadly illuminate the Danon disease phenotype and should prove useful to physicians working with and providing genetic counseling to families with Danon disease. Women with Danon disease present with clinical symptoms and events approximately 15 years after men and report a higher proportion of cognitive and skeletal muscle problems than previously recognized.     

Natural history of rhizomelic chondrodysplasia punctata

Rhizomelic chondrodysplasia punctata (RCP) is a rare autosomal recessive disorder with many associated medical complications. Prior to this study, natural history information about RCP was limited and based on experiences with small populations of affected individuals. We delineate the natural history of RCP through systematic analysis of 35 previously unreported individuals (as well as review of 62 literature cases with respect to survival and cause of death). Survival, growth, and developmental expectations and medical needs are summarized based upon experience with this population. Survival is greater among this population than previously reported, with 90% surviving up to 1 year and 50% surviving up to 6 years. Cause of death is most often respiratory problem. All infants with RCP have joint contractures, bilateral cataracts, and severe growth and psychomotor delays. Recommendations for health supervision of children with RCP and for parental counseling are presented.     

Natural history of allergy to Hymenoptera

One hundred and nineteen patients who had a generalized reaction to a bee sting and who subsequently had a history of being re-stung before desensitization were studied. The reaction, in these 119 patients was as follows: 44.5% had an improved grade of reaction, 42.9% had the same grade of reaction and 12.6% had a worse grade of reaction. Of these 119 patients, 39.5% had only a local reaction to their re-sting. Those patients who were re-stung within 2 weeks (anergic period) or over 5 years after a generalized reaction to a sting had significantly improved response. Results of pretreatment RAST to venoms of hornet, yellow jacket, wasp, honey bee and to phospholipase A appeared to correlate with the clinical signs and symptoms of the previous sting in 75% of cases.     

Fetal brain disruption sequence: a milder variant.

We report on a female infant with severe microcephaly, scalp rugae, overlapping sutures, and telancephalic damage with relatively satisfactory early motor development. This case represents a milder form of the 'fetal brain disruption sequence', which is thought to be the result of an exogenous insult to the developing brain during the second half of gestation.     

Natural history of mosaic trisomy 14 syndrome

Trisomy 14 mosaicism produces a distinct phenotype. Among the 13 reported and 2 additional patients, the following findings were present in more than 90%: growth retardation (15/15), psychomotor retardation (10/10), broad nose (13/14), “dysplastic” and/or apparently low-set ears (15/15), micrognathia (15/15), short neck (11/12), congenital heart disease (14/15), and micropenis and cryptorchidism (6/6). Other frequent findings were prominent forehead (12/14), hypertelorism (8/13), narrow palpebral fissure (7/9), large mouth (10/14), cleft or highly arched palate (10/14), body asymmetry (8/12), and abnormal skin pigmentation (6/10). Sex ratio was 6M:9F. Four patients died before age 4 months, while at least 2 patients survived through teens. One boy died at age 3 years following cardiac surgery. One girl with tetralogy of Fallot showed a remarkable improvement in health after Blalock–Taussig procedure. Although the surviving patients showed moderate growth and mental retardation, the oldest surviving woman at 29 years demonstrates functional language and appropriate self help skills. © 1992 Wiley-Liss, Inc.     

Natural history study of hereditary multiple exostoses

Hereditary multiple exostosis (EXT) is an autosomal dominant disorder in which the clinical hallmark is the growth of bony protuberances from long bones and which can cause a variety of orthopedic deformities. This study sought to further delineate the natural history of EXT. In addition, since previous studies have suggested that there are deviations from Mendelelian expectations in EXT, including incomplete penetrance and a skewed sex ratio, we attempted to confirm or refute these suggestions. Both portions of the study were carried out through retrospective review of 43 affected probands and 137 of their affected relatives. Data are presented concerning frequency and severity of complications of EXT including short stature, sequelae of exostoses, occurrence of malignant degeneration of exostoses, and problems in pregnancy and delivery of affected females. Only 2.8% of the total affected population had experienced exostosis-related malignancy, an estimate which is considerably less than earlier reports would suggest. Penetrance was 100%. There was an excess of males within the entire affected population (104:76) and within identified probands (28:15). However, the male to female ratio was unskewed in nuclear families (probands, affected sibs, and parents). The excess of males appears to be related to males having more severe and more frequent complications of EXT than having any primary genetic origin. © 1995 Wiley-Liss, Inc.