Chirane Viseskul

Familial bilateral renal agenesis and hereditary renal adysplasia

This paper reports three kindreds (A, B, C) with familial bilateral renal agenesis (BRA). Etiologically, BRA is considered a multifactorially determined disorder; pathogenetically it is viewed as a developmental field defect involving absence of both kidneys and ureters in all cases, and in other cases an associated spectrum of related field defects which range from absence of the uterus and vagina to sirenomelia. In BRA, Potters syndrome represents a symptomatic deformity complex due to oligohydramnios.Two additional kindreds (D and E) in this paper show that unilateral absence of a kidney may occur in relatives of a propositus with severe bilateral renal “adysplasia”. The former defect is designated “unilateral renal aplasia” and is presumed to be a less severe form of bilateral renal adysplasia. In these two families, and in two others from the literature, autosomal dominant inheritance seems responsible for the presence of unilateral aplasia and bilateral adysplasia in different family members; this newly recognized genetic trait, is being designated “hereditary renal adysplasia (HRA)”. In women with unilateral renal aplasia the associated tubal and uterine malformation may be responsible for prematurity plus an increased risk of spontaneous abortion.

Chondrodysplasia punctata — Rhizomelic form

Pathologic, ultrastructural and radiologic studies are described on 3 infants with the rhizomelic form of chondrodysplasia punctata. Radiologic criteria in the young infant include radiolucent coronal clefts dividing all or most of the thoracic and lumbar vertebral bodies, short humeri with flared metaphyses and punctate calcifications commonly present adjacent to the ossified ischial and pubic bones and less commonly in other locations. In late infancy and childhood the radiologic criteria include demineralization in all bones with slow maturation, flat vertebral bodies, short humeri and femora, metaphyseal flaring, especially in the distal humerus, proximal femur and proximal tibia, immature shape of pelvis, and disappearance of the punctate calcifications with advancing age. The histologic changes of the resting cartilage include areas of degenerating cartilage which had become partially calcified, cystic changes with severe disturbance of the maturation of the cartilage at the physeal plate, and the formation of cancellous bone directly on resting cartilage. Ultrastructural changes are characterized by degeneration of chondrocytes, delicate collagenous fibrils without visible periodicity, and the presence of flocculent material within greatly distended endoplasmic reticulum.

A fetus with upper limb amelia, “caudal regression” and Dandy-Walker defect with an insulin-depedent diabetic mother

We describe the fetus delivered to an insulin-dependent diabetic woman who had had a previous large, stillborn, non-malformed male infant and a normal female infant. The present fetus had a most unusual combination of malformations which to date had not been described in diabetic embryopathy. The anomalies include: upper limb amelia; “caudal regression” with bilateral absence of the fibulae, unilateral absence of a femur and ipsilateral oligodactyly; undescended testes; atrial septal defect; multiple vertebral and rib anomalies with cervical scoliosis and right webbed neck; left cleft lip and cleft palate; severe micrognathia; left microtia with atresia of the ear canal; and central nervous system defects including hydrocephalus with the Dandy-Walker malformation, asymmetry of the lateral ventricles, abnormal frontal gyral formation, and ependymal and ganglion cell heterotopias of the spinal cord. The pathogenesis of diabetic embryopathy is discussed.

Niemann-Pick Disease Type C

Two sisters with Niemann-Pick Disease Type C suffered from a progressive CNS degenerative disease which ended with death at 8 and 7 years. Light microscopic and histochemical studies revealed storage of lipid (principally sphingomyelin) in the viscera and in the central nervous system (predominantly ganglioside). Complex lipid cytosomes containing stacked membranes, concentric laminated bodies with central dense cores and pleomorphic profiles were seen. Biochemical analysis showed an elevation of sphingomyelin in liver and spleen with normal total sphingomyelinase levels. However, by isoelectric focusing, there was a marked reduction of sphingomyelinase activity in the range of pI 4.6–5.2, whereas normal amounts of more acidic components were found. These data are compatible with autosomal recessive inheritance of a sphingomyelin lipidosis associated with deficiency of isoelectric forms of sphingomyelinase.

The pathologic anatomy of the G syndrome

A detailed anatomic study of the organs of a stillborn male infant with the G syndrome was made.The malformations consisted of a subtle physiognostic appearance with severe micrognathia, penoscrotal hypospadias with descended testes, and failure of closure of the laryngotracheal groove. In addition, respiratory tract defects included lack of lung fissures, short trachea with a high carina and a symmetrical bronchial tree. Minor cardiac malformations of systemic and cardiac venous drainage, and urinary tract anomalies were also present. Developmental, clinical and genetical aspects of the G syndrome were discussed.

Studies of malformation syndromes in man XXXVI: the Pfeiffer syndrome, association with Kleeblattschädel and multiple visceral anomalies

This paper reports sporadic occurrence of the Pfeiffer syndrome with Kleeblattschädel (KS) in a male infant who died at 6 months of pneumonia with signs of increased intracranial pressure and who was found to have hydrocephalus, polymicrogyria, cerebellar herniation, bicuspid aortic valve, a common mesentery, absence of lesser omentum, hypplasia of gallbladder, a single umbilical artery, and multiple eye defects. This case is presumed to represent a new mutation: in other families the Pfeiffer syndrome has been dominantly inherited. The Pfeiffer syndrome is a form of acrocephalosyndactyly and impresses clinically as a mild form of the Apert syndrome. The Kleeblattschädel is an etiologically non-specific developmental field defect (DFC); about two fifths of 51 known cases have apparent thanatophoric dwarfism and about one fifth are probable or possible examples of the Pfeiffer syndrome. The KS-DFC has also been seen in the syndromes of Carpenter, Apert and Crouzon.

The clinical spectrum of congenital contractural arachnodactyly

A case of congenital contractural arachnodactyly with severe cardiovascular malformations is described. This case and two other reports of CCA with congenital heart disease from the literature indicate a wider spectrum of clinical manifestations in CCA than generally assumed. The pattern of abnormalities suggests that the underlying connective tissue abnormality in CCA is “spotty” and not generalized as in such disorders as the Marfan syndrome, Stickler syndrome and arthro-dento-osteo dysplasia.

Generalized gangliosidosis type II (Juvenile GM1 gangliosidosis)

Pathological, histochemical and ultrastructural studies on 3 siblings with GM1 gangliosidosis type II are reported. These studies support a biochemical defect with profound deficiency of β-galactosidase which results in widespread accumulation of the GM1 ganglioside and its asialo derivative in brain and to a lesser extent in viscera, as well as in storage of a keratan sulphate-like mucopolysaccharide. Striking valvular changes in the heart without myocardial involvement were seen in all cases. The histochemical and ultrastructural changes are similar to those seen in GM1 gangliosidosis type I, though less severe. Autosomal recessive inheritance without apparent ethnic predilection seems likely.

X-linked hydrocephalus. Further observations

The neuropathologic findings in a case of hydrocephalus of the X-linked recessive aqueductal stenosis type have been studied and compared with those previously reported from the same pedigree as well as with other cases from the literature. Additional pathological findings not previously recorded included: absence of the septum pellucidum and corpus callosum with malformation of the corpora quadrigemina and partial midline fusion of the fornices and thalami and fusion of thalamus with basal ganglia. These new findings indicate a broader phenotypic spectrum of this form of congenital X-linked recessive aqueductal stenosis than was previously known. Additional data from a diagnostic/genetic study of severely mentally retarded individuals are cited to show that 4 out of 5 familial cases of hydrocephalus without spina bifida are compatible with X-linked inheritance.

Defect of cerebellar Purkinje cell histogenesis associated with type I and type II renal cystic disease

SummaryThe cerebellar vermises from a 1 day old child who died with cystic dysplastic kidneys (Potter Type II) and from a 28 day old who died with infantile polycystic kidneys (Potter Type I) were studied by the Golgi silver method and electron microscopical procedures.Golgi stains showed that Purkinje cells from both cases had the following abnormal characteristics: (1) they retained perikaryal processes even at 37–42 weeks after conception although these processes are normally absent from the cerebellar vermis after 34 weeks of gestation; (2) The Purkinje cell dendrites had dilations at their numerous branchpoints. Ultrastructural studies indicated that climbing fibers remained in contact with the perikaryon of the Purkinje cell in both cases although they are not normally present on the perikaryon after 33 weeks gestation. The 1 day old child (Type II) had unusual synaptic structures of the dyad and serial type. The concurrence of cerebellar and kidney cell maldevelopment in this and a variety of other conditions suggests that there may be a pathogenetic and causal relationship between the two.