Melnick-Needles syndrome: indication for an autosomal recessive form.

We describe three patients with bone changes and the facial characteristics of the Melnick-Needles syndrome (MNS). Associated anomalies (once bilateral glaucoma, twice congenital heart defect) were the reason for referral. The MNS literature also suggests a high frequency of associated anomalies, especially cardiopulmonary malformations. The distribution of the affected relatives, consanguinity of one pair of parents, and absence of similar symptoms in parents and other relatives makes autosomal recessive inheritance of the trait in this family a definite possibility. This is of great importance in genetic counseling, particularly of sporadic cases.

Autosomal dominant idiopathic hypoparathyroidism and nervous system dysfunction: report of three cases and review of the literature.

The neurological manifestations of idiopathic hypoparathyroidism in a father, his son, and his daughter are reported. In all three epilepsy was the first manifestation of the disease. Father and son also showed mental deterioration and striocerebellar symptoms; their CT scans revealed symmetrical calcification in the basal ganglia and dentate nuclei. The extent of this calcification increased during normocalcemia, which was produced by dihydrotachysterol therapy. This indicates that other factors than merely hypocalcemia influence the intracerebral calcifying process. Somatosensory evoked potentials (SSEP) showed an abnormal nonspecific complex, indicating dysfunction of the cortical gray matter. It is suggested that in the evaluation of idiopathic hypoparathyroidism one also must be beware of the possibility of epilepsy, mental deterioration, striocerebellar symptoms, intracerebral calcification and SSEP disturbances.

Autosomal recessive progressive high-frequency sensorineural deafness in childhood.

Autosomal recessive progressive high-frequency sensorineural deafness in childhood occurred in six patients from two families. This progressive sensorineural hearing loss starts mainly in the higher frequencies. There is an abrupt decline in the audiogram that slowly decreases with the increase of the hearing loss in the lower frequencies.

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.

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.

Adult metachromatic leukodystrophy. Arylsulphatase-A values in four generations of one family and some reflections about the genetics.

The authors describe an investigation of Adult Metachromatic Leukodystrophy in a Dutch family, of which two persons were affected. The studies of leukocyte arylsulphatase-A activity were made in 47 members of 4 generations of the same family. The propositus, a 30-year old man, showed a conspicious organic brain syndrome, that progressed in two years to a complete dementia. His leukocyte, liver and kidney arylsulphatase-A activities (ASA) were very low; leukocyte-ASA activity increased after aceto-salicylate. His brother had died at 34 years, after a progressive debelitating neuropsychiatric illness of eight years; postmortem metachromatic leukodystrophy was diagnosed. In all living family members, urine and leukocyte arylsulphatase-A activities were determined. The findings are discussed in relation to the genetics and pathogenesis of this adult form of metachromatic leukodystrophy. Allelic heterozygoty is proposed as inheritance model in this family. Suggestions for further research are made.

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.

[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.

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

Six 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.

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.

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.

The Nathalie syndrome. A new hereditary syndrome.

Deafness, cataract, muscular atrophy, skeletal abnormalities, retardation of growth, underdeveloped secondary sexual characteristics, and electrocardiographic abnormalities are the features of a new, probably hereditary syndrome. Case reports are presented.

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.