Renal magnesium wasting in two families with autosomal dominant inheritance.

Hypomagnesemia due to isolated renal magnesium loss was demonstrated in two unrelated families with autosomal dominant mode of inheritance. Magnesium infusions performed in two patients showed not only a reduced renal magnesium threshold but also a lowered renal tubular maximum for magnesium. All members of both families who presented with hypomagnesemia had also a lowered excretion of calcium in the urine, presumably as a consequence of increased reabsorption in Henle's loop.

An autosomal dominant type of congenital muscular dystrophy.

A family with an autosomal dominant type of congenital muscular dystrophy (CMD) will be reported. In general, an autosomal recessive mode of inheritance is accepted for CMD. In 1980, Kalyanaraman et al reported another family with an autosomal dominant CMD with possible involvement of the central nervous system (CNS). Our report concerns a father and daughter suffering from CMD without CNS involvement. The histological findings, especially some mitochondrial abnormalities in the muscle biopsy were remarkable.

Hereditary congenital facial paralysis.

Hereditary congenital facial paralysis is rare. This paper presents a pedigree of four generations of a family of about 100 members, nine of whom suffer from congenital facial paresis, three with impaired hearing, and three with both facial paresis and impaired hearing. Heredity is dominant with reduced penetrance.

[Hydrometrocolpos, polydactylia and congenital heart defect (the McKusick-Dungy-Kaufman syndrome)]. / Hydrometrocolpos, polydactylie en aangeboren hartafwijking (het McKusick-Dungy-Kaufman syndroom).

The McKusick-Dungy-Kaufman syndrome is characterized by hydrometrocolpos, polydactyly and congenital heart disease. Two of these 3 main symptoms should be present for the diagnosis. Associated anomalies are mainly found in the urogenital tract, the gastro-intestinal tract and the skeletal system. On the basis of 2 patients and the literature the clinical features and the genetic aspects of this syndrome are reviewed. The clinical variability and the severity of the syndrome are stressed. Evidence for an autosomal recessive inheritance is given. Because of the clinical variability it seems preferable to use the term complex rather than syndrome.

Congenital adrenal hypoplasia, progressive muscular dystrophy, and severe mental retardation, in association with glycerol kinase deficiency, in male sibs.

A family is described with three male sibs suffering from congenital adrenal hypoplasia (CAH). In the two surviving brothers the disease is clinically further characterized by a Duchenne type muscular dystrophy, growth failure and severe mental retardation. Laboratory investigations revealed deficient activities of gonadotrophin and glycerol kinase. The clinical, biochemical and genetic findings in ths exceptional family are reported and discussed.

Progressive idiopathic strio-pallido-dentate calcinosis (Fahr's disease) with autosomal recessive inheritance. Report of three siblings.

3 siblings with symmetrical calcifications in the strio-pallido-dentate system are described. Parathyroid function was normal and there were no signs of central or peripheral myelinopathy. This is the 9th family reported with autosomal recessive idiopathic strio-pallido-dentate calcinosis and the first to be investigated by computerized tomography (CT). CT scans appeared to be superior to plain skull radiograms to assess the localization and the extent of the calcifications in vivo. The calcifications were the least extensive in the youngest and the most extensive in the eldest. It is suggested that the calcifying process is a progressive disorder. It seems to start in the dentate nuclei and pons, and subsequently extends to the basal ganglia and to the radiation of the corpus callosum.

Recessively inherited 'pure' spastic paraplegia: case study.

Two brothers with 'pure' spastic paraplegia are presented. Inheritance of their condition probably was autosomal recessive. Clinical onset was in the first decade. Peripheral nerve conduction, visual and brain stem auditory evoked potentials were normal. Somatosensory evoked potentials suggested involvement of the cuneate tract. The relevance of neurophysiological evaluation in familial spastic paraplegia is discussed.

X-linked congenital hydrocephalus.

In this report we describe a Dutch family with ten cases of X-linked recessive congenital hydrocephalus with a high perinatal mortality. In three cases necropsy has confirmed the diagnosis. In the best documented case the most striking features are absence of obstruction or stenosis of the aqueduct and congenital malformation of the cerebral cortex. On the basis of our findings and on reviewing the literature, the hypothesis is put forward that the defective gene on the X-chromosome is responsible for a pathological influence on cerebral cortex development and extraventricular CSF pathways. The expressivity of the genetic defect may be variable, causing extreme phenotypic variants (CHC and/or MR) under the influence of the different modifying genetic or environmental factors. Genetic counselling is difficult in families with no X-linked CHC precedent, since the mutant gene rather produces a communicating HC, secondarily complicated by narrowing of the aqueduct, and as at present there is no way of detecting beforehand heterozygote carriers.

Connatal Pelizaeus-Merzbacher disease with congenital stridor in two maternal cousins.

Two maternal cousins are described with the connatal form of Pelizaeus-Merzbacher Disease (PMD) and congenital stridor. Study of brain biopsy material confirms the diagnosis of PMD. The neuropathological findings are suggestive for the transitional form of this disease. Quantitative morphology gives support to the hypothesis that PMD is a disturbance in maturation of neurons and in myelin formation rather than an active degenerative process. The hereditary transmission is most consistent with a sex-linked recessive pattern. Different X-linked signs seem combined in the presented cases.

Epidemiology of alpha 1-antitrypsin deficiency in the Netherlands.

During a 3-year period, newborns in the eastern part of the Netherlands were investigated for alpha 1-antitrypsin deficiency. Electroimmunoassay was used for screening, followed by Pi typing in suspected cases. In all 95 033 newborns were screened, and a mean frequency of deficiency (phenotypes Pi Z, Pi SZ, and Pi S) of 8.00 in 10 000 was found. The distribution of deficient Pi types over the area was remarkably uneven, Pi type Z being more predominant north and Pi type S south of the Rhine. Cluster areas of alpha 1-antitrypsin deficiency, with frequencies of up to 59.6 in 10 000 live births, occurred mainly in small rural communities. In urbanized areas the frequency of deficiency was lower than the mean.

Idiopathic arterial calcification of infancy.

A description is given of a 15-month-old girl with idiopathic arterial calcifications, detected during life time by X-ray. Radiological examination revealed calcifications in medium-sized arteries, histopathological examination showed distinct abnormalities of small vessels. The patient also had a metageria-like outward and retarded mental and motor development with myolysis. No cardiac failure was present.

Karyotype instability with multiple 7/14 and 7/7 rearrangements.

Chromosomes were studied in a mentally retarded boy with microcephaly, growth retardation, facial erythema, café-au-lait spots, and IgA deficiency. In the lymphocytes there was a remarkable tendency to exchange parts of the chromosomes Nos. 7 and 14, the translocations almost exclusively taking place in bands 7p13, 7q32 and 14q11. Seven different types of rearrangements between Nos. 7 and 14, and some other chromosomal aberrations were found. No abnormalities could be detected in the bone marrow. The patient somewhat resembles those affected with ataxia-telangiectasia or with Bloom's syndrome, but on clinical and cytogenetic grounds these disorders could be excluded. 7/14 Translocations similar to those found in our patient's lymphocytes have been reported to occur very rarely in the lymphocyte cultures of individuals with apparently normal chromosome constitution. A relationship between these phenomena may exist.

2:2 and 3:1 meiotic disjunctions in a carrier of a reciprocal 10/14 translocation.

The offspring of a female with a reciprocal whole-arm translocation between a chromosome No. 10 and a chromosome No. 14 is described. She gave birth to three cytogenetically different children: one with a normal, one with an abnormal but balanced, and one with an unbalanced karyotype. In these three cases, 2:2 disjunctions must have occurred during maternal meiosis. She also had a trisomy 14 abortion, which is assumed to have been caused by a 3:1 meiotic disjunction.

Bloom's syndrome in two Dutch families.

The clinical and cytogenetic data are presented of four children with Bloom's syndrome, who belong to two unrelated Dutch families. The patients showed, in varying degrees, the clinical features most characteristic of the syndrome: stunted growth; telangiectatic facial erythema; sun-sensitivity of the skin; and decreased immuno-competence. In one child the skin lesions were only minor and the diagnosis would probably not have been made if her sib had not been recognized as having Bloom's syndrome. The cytogenetic characteristics of the syndrome were present in all patients. Each showed a high number of chromosomal aberrations and numerous sister-chromatid exchanges per cell.