Liver Transplantation for Severe Alcoholic Hepatitis: Report of a Single Center Pilot Program.

BACKGROUND: Liver transplantation (LT) can significantly improve mortality for severe alcoholic hepatitis (AH). However, this practice remains controversial. Our aim is to report the findings from our institution regarding outcomes for LT in severe AH and to discuss the results of a pilot program for discharging selected patients with close follow-up, in order to demonstrate sustained outpatient sobriety before listing. METHODS: Patient records were reviewed retrospectively from January 1, 2015 to January 17, 2018. The primary outcomes were patient and graft survival after LT. Secondary outcomes included relapse rates after LT, survival for those not transplanted, and reasons for denial among those not approved for transplant listing. RESULTS: A total of 18 patients with severe AH were considered for LT, of which 10 were transplanted and 8 were either denied transplantation or died before completing the evaluation. Patient and graft survival rates were 100% among those transplanted, and only 1 of the 10 patients (10%) returned to harmful drinking. In comparison, 6 of 8 (75%) of patients not transplanted died. Among the 10 patients transplanted, 4 were initially not approved for listing and were discharged with close follow-up, to demonstrate outpatient sobriety. All 4 of those patients demonstrated short-term abstinence and ultimately underwent transplantation, with no instances of relapse post-LT. CONCLUSIONS: Liver transplantation for AH can achieve excellent outcomes with low rates of relapse. Carefully selected patients can be discharged with close monitoring to demonstrate commitment to outpatient sobriety prior to transplant listing.

Ultrastructural investigation of Zimmermann-Laband syndrome.

Zimmermann-Laband syndrome (ZLS) is a very rare autosomal dominant inherited condition characterized by 3 major clinical findings of which gingival hyperplasia are always present. The great heterogenicity of the syndrome is illustrated by the numerous variable clinical findings described in the literature. The purpose of the study was to examine a patient diagnosed with ZLS and to describe possible new characteristics of this rare syndrome, including the ultrastructural morphology using a transmission electron microscope (TEM) of the gingival and dermal fibroblasts. The ultrastrucutral morphology as has not previously been described in the literature. Tissue was collected from the alveolar ridge and skin of the forearm for TEM. TEM studies indicated the presence of prominent fibroblasts situated among numerous regular dense connective tissue bundles. Genetic analysis showed a new chromosomal insertion, ins(12;8)(p11.2;q11.2q24.3), suggesting that the gene responsible for the syndrome lies on chromosome 8.

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping.

HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbrück equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.

Family with autosomal dominant hidrotic ectodermal dysplasia: a previously unrecognised syndrome?

We describe a three-generation family with an autosomal dominant hidrotic ectodermal dysplasia consisting mainly of tricho- and onychodysplasia. One of the patients had supraventricular tachycardia, another had palpitations, and two others had sinus brachycardia. We consider that the clinical manifestations in this family differ significantly from those of the Clouston syndrome (their previous diagnosis) and places them in Group A, subgroup 1-3 (tricho-onychic) of the ectodermal dysplasia classification proposed by Freire-Maia and Pinheiro [1988, "Ectodermal Dysplasias"].

Atypical acrofacial dysostosis syndrome.

We describe a male fetus with a combination of defects, including severe mandibulofacial dysostosis, holoprosencephaly, upper limb deficiency, and microgastria. These abnormalities indicate a severe defect of gastrulation/blastogenesis predominantly affecting cephalad structures. This combination of anomalies has to our knowledge not previously been described. We propose that the anomaly pattern represents either a blastogenesis-related association, or a microgastria-limb deficiency polytopic field defect.

Sutural exostoses, rib hyperostoses, craniosynostosis, mental retardation with focal fat deposition: Proteus syndrome?

We report on a 3-year-old boy with cartilaginous exostoses of the cranial sutures, rib hyperostosis, macrocephaly, metopic craniostenosis, epibulbar dermoid, hyperpigmented macules on the neck, focal fat deposition, and mild mental retardation with marked speech delay. Several of these manifestations were reported previously as an "unknown" by Thanos et al. [1977], with additional clinical information and a diagnosis of Proteus syndrome [Cohen, 1993].

Maternal origin of extra haploid set of chromosomes in third trimester triploid fetuses.

Twenty-six highly polymorphic markers were used to determine the origin of the extra haploid chromosome set in 6 triploid fetuses of type II phenotype. All had reached the third trimester of pregnancy. The extra set was maternal in origin in all cases, supporting previous research indicating longer in utero survival of maternally-derived triploid fetuses. These findings provide evidence for an instance of genomic imprinting in humans.

Acrocallosal syndrome in two African brothers born to consanguineous parents.

We describe two mentally retarded brothers with craniofacial anomalies, polydactyly, and other clinical manifestations compatible with the acrocallosal syndrome (ACS). These are the first black patients from Africa with this diagnosis. They are also the fourth set of sibs described with ACS, and together with the parental consanguinity documented in this family, confirm autosomal recessive inheritance of this syndrome. The clinical manifestations in our patients confirm the intrafamilial variability of the syndrome. Postnatal onset of growth retardation is proposed as an additional manifestation of ACS.

Acromelic frontonasal dysostosis.

We report on 3 male and 2 female infants with acromelic frontonasal dysostosis. All 5 had a frontonasal malformation of the face and nasal clefting associated with striking symmetrical preaxial polysyndactyly of the feet and variable tibial hypoplasia. In contrast, the upper limbs were normal. This rare variant of frontonasal dysplasia may represent a distinct autosomal-recessive disorder. We suggest that the molecular basis of this condition may be a perturbation of the Sonic Hedgehog (SHH) signalling pathway, which plays an important part in the development of the midline central nervous system/craniofacial region and the limbs.

Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) in three neonates.

Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) is a rare, recessive skeletal dysplasia previously reported almost exclusively in Afrikaans speaking South Africans. The condition has been well documented in infants and children. We report on three neonates with SEMDJL, whose presentation highlighted the difficulties inherent in the clinical diagnosis of this condition. SEMDJL may be more widespread than previously considered, as evidenced by the recent documentation of a Guatemalan child with the condition.

Clinical features of Black African neonates with Down's syndrome.

Early reports indicated a low prevalence of Down's syndrome (DS) in black African children. More recent research demonstrates an incidence similar to, or higher than that reported to occur in First World populations. One of the possible reasons for underreporting of DS in Africa, appears to be the lack of recognition of the problem at birth. In this study, the musculoskeletal, central nervous system and craniofacial features are documented in 40 black DS neonates and 50 black control neonates without DS, and the findings are compared with those from a reported series of 37 caucasian DS and 40 healthy newborns. Musculoskeletal and central nervous system features were markedly similar in black and caucasian infants. However, the craniofacial features of the African DS newborns approximated more closely those of the normal African neonates, than was the case in the caucasian DS and normal neonates. This finding may partially explain the underreporting of DS in this population, and it emphasizes the need for a clinical awareness of DS and for complete clinical examination to identify affected infants.

Medical genetics in primary health care.

Medical genetics has been at the forefront of developments in medicine for the last 50 years. This progress has mainly benefited industrialized countries. Due to continuing improvements in the socio-economic and health indices in developing nations more than half of them have now reached a stage where it has become relevant for them to initiate and develop medical genetic services. The WHO foresaw this eventuality in 1985 and further recognised the need to develop community based medical genetic services that are relevant to and can be incorporated into primary health care. The need for primary health care based medical genetic services has subsequently also been accepted in industrialized nations. This paper summarises those primary health care based interventions that can be undertaken to ensure the control of genetic disorders and birth defects.

Down syndrome in black South African infants and children--clinical features and delayed diagnosis.

STUDY OBJECTIVE: Down syndrome (DS), the commonest cause of congenital developmental disability in developed countries, has only recently been shown to have an incidence in black South African neonates as high, and in some studies higher, than currently seen in First-World nations. It has also been reported that the mothers of black African DS newborns and medical and nursing staff have difficulty recognising and diagnosing DS in black neonates. The aims of this study were to document the clinical features of black DS infants and children, compare these to the features of previously documented DS infants and children from other ethnic groups, and finally to ascertain if and for how long the difficulties recorded in diagnosing DS in blacks extended into infancy or childhood. DESIGN: This was a prospective, genetic clinic-based study, entailing clinical evaluation of black DS infants and children 3 months of age and older, and the administration of a questionnaire to the mothers of these patients. SETTING: Genetics clinics at Kalafong and Ga-Rankuwa hospitals, Pretoria, and at Mankweng, Siloam, Groothoek, Nkhensani and Elim hospitals in the Northern Province. MAIN RESULTS: Fifty-five DS infants and children were assessed. Their clinical features were comparable to those of children from other ethnic groups. Congenital heart disease (CHD) was recorded in a significantly higher percentage of infants under 12 months of age (51.9%) than children 13 months of age or older (25%). Only 9 (16.4%) of these DS patients were clinically diagnosed in the neonatal period, and a further 18 (32.7%) at between 1 and 6 months of age. More than half (28 or 50.9%) were 7 months of age or older when initially clinically diagnosed. Maternal self-initiated awareness of a problem with their infant or child preceded clinical diagnosis in 32 (58.2%) patients. CONCLUSIONS: The difficulties experienced by medical and nursing staff in diagnosing DS in black neonates extends into infancy and childhood, despite the fact that the clinical features of black DS infants and children do not differ from those seen in DS patients in other ethnic groups. The prevalences of CHD in black DS infants and children suggest that CHD is a significant cause of mortality in black DS patients.

Four cases of trisomy 18 syndrome with limb reduction malformations.

Limb reduction malformations of the arms are well documented in the trisomy 18 syndrome. Four cases of trisomy 18 syndrome with limb reduction malformations of the legs are described and compared with the upper limb malformations.

South African geneticists' attitudes to the present Abortion and Sterilisation Act of 1975.

STUDY OBJECTIVE: To ascertain the attitudes of clinical geneticists and genetic counsellors practising in South Africa to the current Abortion and Sterilisation Act of 1975 (the Act). DESIGN: Postal questionnaire. MAIN RESULTS: Ninety-two per cent of the questionnaires were returned, and the responses were comparable to those of the South African Society of Obstetricians and Gynaecologists in 1990 and the Society of Psychiatrists of South Africa in 1992. No respondent felt that the Act should be more restrictive, and only 4 (17.4%) felt that it was acceptable in its present form. Section 3(1)(c) of the Act, which relates to termination of pregnancy (TOP) on genetic grounds, was acceptable in its present form to 13 respondents (56.5%), but 16 (69.7%) considered that TOP on genetic grounds should not be curtailed in future legislation. CONCLUSION: The geneticists' attitudes to the present Act concurred with those of the obstetricians and psychiatrists previously documented, and confirmed the need for review of the Act. All three specialist groups appeared to support an increase in the indications for legal TOP rather than the introduction of TOP on request up to a specified post-conceptual age. With regard to Section 3(1)(c), the geneticists' responses indicated an acceptance of the limitations of the present Act, coupled with concern about the implications of future changes to this section of the Act.

Maternal non-recognition of Down syndrome in black South African infants.

Down syndrome (DS), one of the commonest causes of mental retardation in Caucasoids, has only rarely been described in Africa. In previous studies it was suggested that there may be clinical difficulties in making the diagnosis in African neonates. In the present study data were collected by means of a questionnaire administered partly before and partly after a genetic counselling session, to 35 mothers of African infants with DS. The results show that 83% of these mothers did not recognise any facial difference between their affected infant and other normal infants and 57% did not observe any other physical differences. After counselling, 40% of the sample still did not accept that their infant was different from other newborns. Only one mother was aware of infants with similar characteristics. These findings suggest that if mothers themselves cannot see the differences between their DS children and normal children, clinical diagnosis based on physical stigmata may be difficult. Furthermore, acceptance of the diagnosis may be retarded until delayed mile-stones can be observed in the affected infants.