The Bannayan syndrome: an autosomal dominant disorder consisting of macrocephaly, lipomas, hemangiomas, and risk for intracranial tumors.

The Bannayan syndrome is a disorder consisting of macrocephaly, alterations of linear growth, and benign mesodermal hamartomas--primarily lipomas and hemangiomas. The purpose of this report is to present a family with the Bannayan syndrome, confirming the genetic etiology of the disorder and demonstrating that affected individuals are at risk for developing intracranial neoplasms. This report brings to seven the number of cases reported in the literature.

A second patient with partial deletion of the short arm of chromosome 3: karyotype 46,XY,del(3)(p25).

A child with monosomy for the distal part of the short arm of chromosome 3 is presented. Altered features include prenatal onset growth deficiency, postaxial polydactyly, ptosis, ear anomalies, and a triangular facial appearance. In addition to generalised delay in psychomotor development, specific problems in visual attention were present. Comparison with the previously reported case suggests that the phenotype observed constitutes a clinically recognisable pattern of malformation.

Presentation of mucopolysaccharidosis VII (beta-glucuronidase deficiency) in infancy.

A child is presented with mucopolysaccharidosis VII (beta-glucuronidase deficiency), bringing to six the number of reported patients with the infantile onset form of this disorder. This patient exhibited the following features, previously unrecognised as part of this syndrome: presentation in the neonatal period, progressive joint contractures, and hydrocephalus. This child's course and data from published reports indicate that mucopolysaccharidosis VII, unlike the other known mucopolysaccharidoses, is clinically recognisable in the newborn period and is most likely to be associated with moderate mental deficiency which does not progress over time.

The vascular pathogenesis of gastroschisis: intrauterine interruption of the omphalomesenteric artery.

Recognition of the disruptive vascular nature of the structural defects associated with gastroschisis and an appreciation of the embryology of the umbilical region suggest that gastroschisis results from an intrauterine interruption of the omphalomesenteric artery. This mechanism accounts for the usual location of gastroschisis to the right of the umbilical cord, the integrity of the rectus muscles in affected children, and many of the clinically observed differences between gastroschisis and omphalocele. The vascular basis of this defect explains its negligible recurrence risk and should alert the clinician to the possibility of concomitant structural defects of a similar pathogenesis.

Compression-related defects from early amnion rupture: evidence for mechanical teratogenesis.

The features of 27 cases of limb/body wall deficiency (formerly termed cyllosomus and pleurosomus) were evaluated and the anomalies were interpreted as being band-related defects and/or compression-related defects. The latter included limb deficiency, body wall deficiency, neural tube defects, scoliosis, postural deformations, growth deficiency, and short umbilical cord. It is hypothesized that the single event of early amnion rupture can explain both the band-related defects and the compression-related defects. Experimental animal studies are in accord with this hypothesis; amnion puncture of rat fetuses during early gestation produces a comparable array of defects. The term amnion rupture sequence is suggested to describe the overall pattern of malformation that results from amnion rupture whether these defects are band related, compression related, or a combination of the two. There is considerable variation in the phenotype of amnion rupture sequence, with limb/body wall deficiency representing the more severe end of the spectrum. It is important to recognize and correctly diagnose amnion rupture sequence because it is usually a sporadic event.

Vascular etiology of disruptive structural defects in monozygotic twins.

Two infants with structural defects previously undescribed in the survivor of a monozygotic twin pair are reported. One infant had hydranencephaly and a spinal cord transection, with an associated dead monozygotic co-twin of 24 weeks gestation; the other child had complete atresia of the colon and a horseshoe kidney, with a deceased co-twin of approximately six weeks gestation. These defects are presumed to be the result of in utero disruption of previously normally formed structures. They occur secondary to vascular exchange from a dead to a living monozygotic twin through placental vascular anastomoses. As illustrated by the two children described, the nature of the vascular defects seen in the survivor of a monozygotic twin pair depends on the time during gestation at which the co-twin dies. Recognition of the disruptive vascular etiology of the structural defects outlined in this report will allow for appropriate counseling with respect to the negligible recurrence risk for similar vascular accidents.

Determining role of the optic vesicle in orbital and periocular development and placement.

Nine patients with aberrations in development and placement of the eyes and periocular structures who also had serious defects in central nervous system development were evaluated in order to better understand normal ocular development. Included were an incompletely developed twin stillborn infant who lacked both eyes and the nose, a stillborn infant with cyclopia hypognathia, 6 spontaneous abortuses with varying degrees of holoprosencephaly, and a 17-year-old male with a serious defect in central nervous system development whose right eye was positioned laterally above the right ear. In all cases, evidence indicates that orbital and periocular structures are determined by the underlying optic vesicle rather than independently derived as has been suggested by previous studies.

Intrauterine constraint and craniosynostosis.

Intrauterine constraint is responsible for a number of structural defects of the craniofacial and peripheral skeleton including plagiocephaly, micrognathia, congenital hip dislocation, and talipes equinovarus. This report describes five infants with serious craniofacial alterations, all attributable to intrauterine constraint. All five children had clinical and laboratory evidence strongly suggestive of craniosynostosis. In three of the five, sutural fusion was documented either at operation or at necropsy. In the other two the clinical course indicated that true synostosis was not present. In all cases the sutural involvement corresponded to the dimension in which head growth had been restricted. This determaination was based upon an assessment of the other craniofacial alterations that were present. The etiology of the intrauterine constrain was different in each case. Factors involved included breech presentation, primagravidity, uterine malformations, amniotic bands, and defects in fetal neuromuscular development, all of which are known to produce fetal deformations. As further evidence of severe constraint, fetal activity was greatly reduced during four of the five pregnancies. There was no history of craniosynostosis in other family members. We propose that in utero compression may lead to a spectrum of craniofacial defects that includes craniosynostosis when the constraint is particularly prolonged. The data suggest that mechanical forces may play a role in the etiology of some cases of craniosynostosis. The fact that head shape spontaneously remolded in one of the five cases suggests further that surgical correction may not be required in all cases in which constraint is the suspected etiology of the deformation. (Neurosurgery, 6: 39-44, 1980).

The Cockayne syndrome: an evaluation of hypertension and studies of renal pathology.

Three children with renal disease, hypertension, and the Cockayne syndrome were evaluated. All patients had severe hypertension; peripheral vein renin was elevated in two patients. Renal biopsy specimens from two patients were studied by light microscopy, electron microscopy, and immunofluoresence. Immunohistologic studies demonstrated deposits of immunoglobulin and complement in the vessels and glomeruli of the first patient; deposits of immunoglobulin and complement were seen in the glomeruli of the third patient. Also electron-dense deposits were seen in the glomerular basement membrane of the third patient. Circulating immune complexes were detected by the Raji cell and Clq binding techniques in this child as well. Both hypertension and renal disease are frequent complications of the Cockayne syndrome.

The amniotic band disruption complex: timing of amniotic rupture and variable spectra of consequent defects.

Seventy-nine patients with the amniotic band disruption complex, including 54 infants with multiple system involvement and 25 with affected limbs alone, were evaluated. No two cases of the disorder were exactly alike. Defects varied from simple digital band constrictions to major craniofacial and visceral defects; fetal death may also occur. Amniotic rupture appeared to cause injury through three basic mechanisms: (1) interruption of normal morphogenesis; (2) crowing of fetal parts; and (3) disruption of previously differentiated structure. Comparison of 35 cases in which the timing of amniotic rupture could be estimated suggests that early amniotic rupture results in multiply affected infants who are frequently aborted or stillborn, whereas later rupture results primarily in limb involvement. Our findings indicate that both the spectrum of the developmental pathology and the nature of fetal outcome are determined by the timing of amniotic rupture. Appreciation of the mechanism which explains the disparate appearances of infants with the amniotic band disruption complex will allow more acurate diagnosis and appropriate counseling with respect to the sporadic nature of the disorder.

The Aase syndrome in a female infant.

This report describes a 2-month-old female with the Aase syndrome, bringing to 8 the total number of cases of this disorder. Features include triphalangeal thumbs and congenital hypoplastic anaemia. The occurrence of this disorder in sibs born to unaffected parents and in both sexes makes autosomal recessive inheritance the most likely aetiology.

Two forms of cutis laxa presenting in the newborn period.

Two infants are described with congenital cutis laxa. They represent two distinct disorders. In the first, congenital cutis laxa is associated with a generalized disorder of elastic tissue in which there may be diaphragmatic or other hernias, diverticula of the gastrointestinal or urinary tract and infantile emphysema. The disease is fatal often within the first year. In the second, congenital cutis laxa is associated with widely patent anterior fontanel, a variety of malformations, and retarded growth and development. Recognition of these distinct syndromes in the newborn period and their recessive inheritance permit realistic discussion of the prognosis which is very different from the benign dominant forms of cutis laxa.

Dysmorphology: an approach to diagnosing children with structural defects of the head and neck.

In dealing with a child with a structural defect, an overall diagnosis must be formulated. Such a diagnosis makes it possible to provide genetic counseling for the parents and an accurate prediction relative to such a child's future development. Because there are a great many abnormalities involving the head and neck, it is hoped that the approach set forth in this article will allow for a systematic narrowing of the diagnostic possibilities. Nomenclature is established. Prenatal-onset defects are described, including both single primary defects (malformations and deformations) and multiple malformation syndromes (chromosomal abnormalities, genetic disorders, defects resulting from teratogenic factors, and disorders of unknown etiology). Genetic and environmental factors of postnatal developmental problems are also discussed.

A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegetarian.

We studied a six-month-old infant with severe megaloblastic anemia, coma and hyperpigmentation of the extremities. He was found to have methylmalonic aciduria (79 mumol per milligram of creatinine) and homocystinuria (0.85 mumol per milligram of creatinine). Additional biochemical abnormalities included cystathioninuria, glycinuria, methylcitric aciduria, 3-hydroxypropionic aciduria and formic aciduria. The concentration of vitamin B12 in the serum was 20 pg per milliliter. This severe nutritional deficiency was a consequence of inadequate intake, for the infant was exclusively breast-fed by a strictly vegetarian mother who manifested methylmalonic aciduria. Our observations emphasize the importance of educating strict vegetarians about the deficiency of vitamin B12 in their diets and the importance of vitamin B12 supplementation.