Velo-cardio-facial syndrome vs. CHARGE "association".
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Abnormalities, Multiple↗
Biomedical subjects
R A Pagon
Publications and source records attributed to R A Pagon.
Diagnostic approach to the newborn with ambiguous genitalia.
When assessing an infant with ambiguous genitalia, there are some important points to remember: Do not delay the evaluation of a patient with ambiguous genitalia. A delay may expose the patient unnecessarily to a life-threatening situation, such as a salt-losing crisis associated with 21-hydroxylase deficiency or one of the testosterone biosynthetic defects. Also, it is unfair to expect the family to be able to deal emotionally with the uncertainty of unresolved gender assignment. Never perform a buccal smear. There is absolutely no indication for performing a buccal smear at any point in the evaluation of any patient with ambiguous genitalia. Use of a buccal smear to determine gender assignment was helpful decades ago, before analysis of human chromosomes was possible. With current cytogenetic methodologies that can detect chromosomal mosaicism and subtle abnormalities of the X and Y chromosomes, there is never an indication to perform a buccal smear. Never make a gender assignment on the basis of the appearance of the external genitalia alone. The chromosomal sex and gonadal sex need to be determined first. The parents' feelings regarding the desired sex of the child, gender identity and fertility need to be discussed. Once there are sufficient data, gender assignment can be made. Gender assignment should be made as soon as possible after birth, but absolutely should be made by 18 months of age, when children develop gender identity. Never equivocate in the assignment of gender. The parents and the physicians must be absolutely certain of the gender assignment and must view their decision as final. Follow-up visits with the family ideally include an assessment of their acceptance of the gender assignment of the child. If there is ambivalence, steps must be taken to identify the source of ambivalence and to clarify the issues.
Disorders of Sex Development↗
Holoprosencephaly: prenatal sonographic diagnosis.
Fourteen cases of holoprosencephaly (HP), including 10 cases of alobar HP and four cases of semilobar HP, were identified by prenatal sonography. Intracranial and extracranial findings were reviewed to determine the accuracy and spectrum of the sonographic features. All 14 cases were reliably distinguished from other causes of fetal hydrocephalus (n = 58) detected during the same period by demonstrating absence of the midline echo (falx cerebri and interhemispheric fissure), fusion of the thalami, and abnormal ventricular configuration. Four cases of semilobar HP demonstrated incomplete fusion of the thalami and partial separation of the ventricles compared with alobar HP. Eight cases demonstrated a dorsal cyst including five with alobar HP and three with semilobar HP. One case demonstrated an unusual extraaxial fluid collection surrounding the brain, thought to be from rupture of a dorsal cyst. Facial features that were identified included a proboscis (three cases), midline facial cleft (three cases), and hypotelorism (five cases). Extracranial abnormalities that were identified included polydactyly (two cases), renal dysplasia (two cases), omphalocele (one case), and fetal hydrops (one case). We conclude that fetuses with HP can exhibit a spectrum of sonographic findings and that alobar or semilobar HP is reliably distinguished from other causes of fetal hydrocephalus by distinctive intracranial findings.
Abnormalities, Multiple↗
Williams syndrome: features in late childhood and adolescence.
Nine children with the Williams syndrome were evaluated for physical, neurodevelopmental, and behavioral characteristics to record the natural history of this disorder. The study subjects, who ranged in age from 10 years to 20 years, generally showed lower than expected cognitive functioning with four of the nine functioning in the severely retarded range. However, all the children showed uneven developmental profiles, compared to measured IQ, with reading abilities exceeding the expected level and visual-motor skills deficient for overall performance expectations. All but one child had evidence of supravalvular aortic stenosis on echocardiography, but there was little morbidity from cardiovascular disease in this group of patients. Although all had grown at or below the fifth percentile in early childhood, seven now were above the fifth percentile for height. Personality attributes that characterize younger children with Williams syndrome persisted in this group of older children.
Achievement↗
Molecular detection of a translocation (Y;15) in a 45,X male.
A 45,X male individual was shown to have a translocation of Y-chromosome material to the short arm or proximal long arm of chromosome 15. This translocation was detected by genomic DNA blotting and in situ hybridization with Y-chromosome-specific DNA probes.
Chromosome Banding↗
Calvarial hyperostosis: a benign X-linked recessive disorder.
We report a family with what appears to be a unique X-linked recessive disorder of isolated hyperostosis of the calvarium. Although irregularity of the calvarium and exophytic prominences of the frontoparietal bones were apparent in infancy, premature cranial suture closure did not occur and there was no evidence of increased intracranial pressure despite a Luckenshadel appearance of the skull. Other membranous bones and the tubular bones were not involved. Calvarial bone biopsy from one patient showed vacuolated histiocytes suggesting a storage disease; however, neurologic deterioration, hepatosplenomegaly, and dysostosis multiplex did not occur. The affected family members had normal stature, normal occipitofrontal circumference, and no other medical problems. The biochemical basis of this disorder is not known. Although storage of abnormal material is possible, the long-term prognosis seems favorable.
Female↗
Retinal neovascularization in Potter's syndrome secondary to renal agenesis.
Abnormalities of retinal vascularization were observed in a male stillborn at 33 weeks gestation with Potter's syndrome secondary to renal agenesis. Each eye had a persistent tunica vasculosa lentis and hyaloid artery as well as enlarged intraretinal vessels and a sharply demarcated avascular peripheral retina. Light microscopy revealed marked proliferation of capillaries and mesenchymal spindle cells of the retina. Electron microscopy of the retinal vascular endothelial cells revealed intact tight junctions with no fenestrations. Spindle cells had gap and intermediate junctions that appeared normal in number and morphology.
Amniotic Fluid↗
'Leopard spot' retinopathy in Warburg syndrome.
A female infant with brain and muscle abnormalities characteristic of Warburg syndrome had an atypical retinal dysplasia which appeared clinically as a 'leopard spot' retinopathy. The retinal histology is described in detail and is remarkable for periodic thinning of the inner nuclear layers and for isolated rosettes in the periphery. We believe 'leopard spot' retinopathy is yet another ocular manifestation of the Warburg syndrome.
Abnormalities, Multiple↗
Kabuki make-up syndrome in a Caucasian.
A 20-year-old Caucasian female with the Kabuki make-up syndrome had adolescent onset cataracts and delayed sexual maturation with evidence of primary ovarian dysfunction. These features have not been described in other patients with this disorder, all of whom have been younger. This patient also had cystic fibrosis, which may be a fortuitous association.
Adult↗
Reevaluation of Russell-Silver syndrome.
Russell-Silver syndrome was reevaluated 2.9 to 13.0 years after initial diagnosis in 15 patients. At follow-up, five of the 15 patients exhibited late catch-up growth and had normal height, six had developmental delays or mental retardation, and asymmetry was present in five. Given the great variability in the long-term prognosis for growth and development in patients with Russell-Silver syndrome, there is a need to reevaluate this syndrome and its clinical implications.
Adolescent↗
Female pseudohermaphroditism with anorectal, müllerian duct, and urinary tract malformations: report of four cases.
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Abnormalities, Multiple↗
Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder.
We report two families in which a non-progressive spinocerebellar syndrome and a sideroblastic anaemia are segregating together in an X linked recessive fashion. Four males in two generations of one family and a fifth male from an unrelated family had both conditions. Both the sideroblastic anaemia and the spinocerebellar syndrome differ from those which have previously been reported to be inherited in an X linked recessive manner. The association of these two clinically distinct disorders in two unrelated families suggests that they are either two closely linked loci which have undergone simultaneous mutation or pleiotropic effects of an altered allele at a single locus. All the heterozygous women had normal neurological examinations and normal haematocrits and red cell indices. Some had ring sideroblasts on bone marrow examination, a dimorphic peripheral blood smear, and raised serum free erythrocyte protoporphyrin, suggesting that a proportion of heterozygotes can be detected by appropriate haematological studies.
Anemia, Sideroblastic↗
Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome.
We are reporting a male patient who suffered from chronic granulomatous disease associated with cytochrome b-245 deficiency and McLeod red cell phenotype, Duchenne muscular dystrophy, and retinitis pigmentosa. On cytogenetic analysis, he seemed to have a very subtle interstitial deletion of part of band Xp21. Since it was impossible to know whether this material was truly deleted or inserted elsewhere in the genome, somatic cell and molecular studies were carried out. In somatic cell hybrids, the deleted X chromosome was isolated on a Chinese hamster background. Southern blot analysis with 20 single-copy probes, that had been mapped to the X short arm, led to the discovery of one (probe 754) that is missing from this patient's X chromosome and also from his total DNA. This proves that he, indeed, has a deletion rather than a balanced insertion. The results provide cytological mapping information for the X-linked phenotypes present in this patient. Furthermore, probe 754 recognizes a restriction fragment length polymorphism of high frequency that makes it the most powerful probe currently available for linkage studies with X-linked muscular dystrophy.
Animals↗
X-inactivation patterns in lymphocytes and skin fibroblasts of three cases of X-autosome translocations with abnormal phenotypes.
X-inactivation patterns were studied by replication analyses both in lymphocytes and skin fibroblasts of two patients carrying balanced X-autosome translocations, t(X;10)-(pter;q11) and t(X;17)(q11;q11), and one patient with an unbalanced translocation t(X;22)(p21;q11). Preferential late replication of the normal X chromosome was found in lymphocytes of both patients carrying balanced translocations and in skin fibroblasts of the patient carrying the translocation t(X;17). However, skin fibroblasts of the patient with a translocation t(X;10) showed preferential late replication of the abnormal der(X) chromosome with no spreading of late replication to the autosomal segment. In the case of unbalanced translocation t(X;22) there was preferential late replication of the der(X) chromosome both in lymphocytes and skin fibroblasts. The abnormal phenotype of the patients is discussed in relation to the observed X-inactivation patterns and the variability of the patterns in different tissues.
Adult↗
Separation of retinoblastoma and esterase D loci in a patient with sporadic retinoblastoma and del(13)(q14.1q22.3).
A chromosome 13 deletion in a patient with sporadic retinoblastoma appears to have separated the loci for retinoblastoma and esterase D. This study indicates that: (1) the retinoblastoma locus is distinct from the esterase D locus; and (2) the linear order of these genes is centromere-esterase D-retinoblastoma.
Carboxylesterase↗
Septo-optic dysplasia with digital anomalies.
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Abnormalities, Multiple↗
Müllerian anomalies and renal agenesis: autosomal dominant urogenital adysplasia.
We report two families in which müllerian anomalies or renal agenesis appeared to be caused by an autosomal dominant gene that produces unilateral or bilateral renal agenesis and a spectrum of müllerian anomalies. This single gene disorder may account for the high incidence of müllerian anomalies observed in females with bilateral renal agenesis and the increased frequency of renal anomalies in patients with müllerian malformations. The range of müllerian anomalies in this disorder includes bicornuate uterus, uterus didelphys, Rokitansky- Kuster -Hauser syndrome (vaginal atresia with or without absence of the uterus), and total müllerian aplasia. Gene expression is not sex limited. Affected males can have bilateral or unilateral renal agenesis, and possibly may have unilateral or bilateral absence of the vas deferens or seminal vesicles. We suggest that autosomal dominant urogenital adysplasia is common, but underdiagnosed because of the deceptive variability in gene expression. In addition, reduced gene penetrance and reduced biologic fitness from lethal renal anomalies or genital tract anomalies may obscure the autosomal dominant nature of this disorder in most families.
Adult↗
Arteriohepatic dysplasia: phenotypic features and family studies.
Arteriohepatic dysplasia (AHD) is a disorder characterized by intrahepatic cholestasis and peripheral pulmonary artery stenosis. We have reviewed the phenotypic features in the 56 previously reported cases and 7 persons from our institutions with AHD to summarize the type of cardiac, hepatic, facial, ocular and skeletal manifestations observed in this disorder. Family studies evaluating first-degree relatives of patients with AHD are compatible with an autosomal dominant mode of inheritance with reduced penetrance and variable expressivity.
Abnormalities, Multiple↗