B. G. A. ter Haar

Aplasia of tibia with split-hand/split-foot deformity. Report of six families with 35 cases and considerations about variability and penetrance.

SummarySix families with a total of 34 affected persons with the syndrome of tibial aplasia and ectrodactyly are reported. The spectrum of malformations is compared to that of 99 familial cases from the literature. The full-blown syndrome consists of bilateral aplasia of tibiae and split-hand/split-foot deformity. Additional malformations may be distal hypoplasia or bifurcation of femora, hypo- or aplasia of ulnae, and minor anomalies such as aplasia of patellae, hypoplastic big toes, postaxial and intermediate polydactyly in connection with split-hand deformity, and cup-shaped ears. The mildest visible manifestation may be hypoplastic big toes, the severest is tetramonodactyly or transverse hemimelia. This disorder is autosomal dominantly inherited. The penetrance is markedly reduced.

Progressive Idiopathic Strio-Pallido-Dentate Calcinosis (Fahr’s Disease) with Autosomal Recessive Inheritance

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.

A presumptive tetrasomy for the short arm of chromosome 9

SummaryFor the identification of an extra chromosome in a female child a number of recently developed staining techniques were used.The extra element found in 86% of the patients peripheral lymphocytes resembles an isochromosome for the short arm of chromosome No. 9, in which case a tetrasomy for this arm would exist. The clinical findings in our patient were compared with those in patients reported to have extra chromosome 9 material.

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

2Department of Pediatrics, Groot Ziekengasthuis, s Hertogenbosch, The Netherlands

Karyotype Instability With Multiple 7/14 and 7/7 Rearrangements

SummaryChromosomes 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 Blooms syndrome, but on clinical and cytogenetic grounds these disorders could be excluded.7/14 Translocations similar to those found in our patients 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.

Trisomy for the short arm of chromosome No. 10

The clinical and cytogenetic data are presented of a child with multiple congenital malformations, including cystic kidneys. A trisomy for at least the larger part of the short arm of chromosome No. 10 in association with a translocation between chromosomes Nos. 10 and 14 was found in peripheral blood lymphocytes and skin fibroblasts. Both the mother and a younger sib were balanced carriers of the translocation.

Immune responses in four patients with Bloom syndrome.

Abstract Immunological examinations of four patients with Bloom syndrome, belonging to two families, revealed some disturbances of the immune function. All patients had decreased levels of at least one class of immunoglobulins. The disturbances of the lymphocyte stimulation tests demonstrated a remarkable similarity in the siblings: decreased stimulation in vitro by phytohemagglutinin (PHA) and pokeweed mitogen (PWM), low responses on stimulation by specific antigens, and diminished responder capacity in mixed lymphocyte reaction (MLR) in both patients of family I: normal stimulation in vitro by PHA and PWM, high responses on stimulation by specific antigens, and diminished responder capacity in MLR in both patients of family II. This remarkable difference in expression of the defect between both families could be the expression of a genetic heterogeneity.

Bloom's syndrome in two Dutch families

The clinical and cytogenetic data are presented of four children with Blooms 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 Blooms syndrome.

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.

Epidemiology of alpha 1 -antitrypsin deficiency in the Netherlands

SummaryDuring a 3-year period, newborns in the eastern part of the Netherlands were investigated for alpha1-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 PiZ, PiSZ, and PiS) 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 alpha1-antitrypsin deficiency, with frequencies of up to 59.6 in 10 000 liver births, occurred mainly in small rural communities. In urbanized areas the frequency of deficiency was lower than the mean.