bluuebunny/crossref_metadata_2025 huggingface dataset:
Noonan syndrome: The changing phenotype
Authors: Allanson J. E. , Hall J. G. , Hughes H. E. , Preus M. , Witt R. D. , Opitz John M. , Reynolds James F.
Published: June 2005

Among the multiple congenital anomalies (MCA) syndromes, the Noonan syndrome (NS) is a cardiofacial syndrome in which affected individuals may be short and mildly mentally retarded. Autosomal dominant inheritance of Noonan syndrome with variable expressivity has been documented in many families. Genetic heterogeneity has been postulated in Noonan syndrome because of the wide phenotypic variability, the relatively high incidence, and the occasional recurrence in sibs with apparently normal parents. Clinical variability is usual in autosomal dominant disorders, and mildly affected individuals may be difficult to recognize as gene carriers. Thus, a family with two or more affected children may simulate autosomal recessive inheritance.

We have studied serial and family photographs of NS individuals in order to assess the likelihood of gene carriers' being missed in genetic sutdies. We have confirmed wide clinical variability within families, and more importantly, we have documented marked change of phenotype with age from the newborn period, infancy, childhood, and adolescence to adulthood. Manifestations in adults may be subtle and some without a known heart defect or other medically significant problems may have been considered normal in the past.

Our study, while not ruling out causal heterogeneity, suggests that the change of phenotype with age may have been falsely perceived as clinical heterogeneity. A particular and subtle phenotype must be searched for in parents of affected children.
Gauher disease: Comparative study of acid phosphatase and glucocerebrosidase in normal and type‐1 Gaucher tissues
Authors: Choy Francis Y. M. , Opitz John M. , Reynolds James F.
Published: June 2005

Acid phosphatase activity was determined in serum, cultured fibroblasts, and peripheral blood lymphocytes of six splenectomized adult patients with non‐neuropathic Gaucher disease in two Canadian families. Elevated levels of serum acid phosphatase activity (520–711% of normal) were found in four patients who also developed orthopedic complications associated with Gaucher disease, including intermittent bone pain, arthritis, collapse of femoral head, and pathological fractures. Serum acid phosphatase activity in two patients who do not have bone involvement were found to be within the normal range. Contrary to the serum enzyme, acid phosphatase activity in lymphocytes and cultured fibroblasts of all of the patients was within the normal range. Deficient glucocerebrosidase (7.5–15.5% of normal) and acid β‐glucosidase (13.8–27.8% of normal) activities were noted in all probands. Similarly, normal levels of fibroblast and lymphocyte acid phosphatase activity were found in Gaucher heterozygotes whose glucocerebrosidase activity was about 50% of normal. Acid polyacrylamide gel electrophoresis and acid phosphatase activity staining of the patients' sera showed that the elevated acid phosphatase is isozyme type 5 of osteoclastic origin. The apparent Michaelis constant, Km, of fibroblast glucocerebrosidase for the natural substrate was 0.6 ± 0.1 mM for controls and 0.6±0.2 mM for the patients. These data suggest that the assay of serum acid phosphatase activity for the presumptive diagnosis of Gaucher disease is not completely reliable and that the elevated level of serum acid phosphatase in Gaucher disease is most likely a secondary phenomenon which may be indicative of bone involvement in some patients with this disorder. It also demonstrates the clinical heterogeneity of type 1 Gaucher disease, even among full sibs of the same heterozygous parents.
The “muscular variant” of Pompe disease: Clinical, biochemical and histologic characteristics
Authors: Temple Julia K. , Dunn David W. , Blitzer Miriam G. , Shapira Emmanuel , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 2‐yr‐old boy with progressive muscular weakness and respiratory failure. There was no clinical evidence of heart muscle involvement. Autopsy showed marked intralysosomal glycogen deposition in skeletal muscle and liver with no histological evidence of glycogen deposition in cardiac muscle. The activity of the lysosomal enzyme α‐1,4‐glucosidase was deficient in skin fibroblasts, skeletal muscle, cardiac muscle, and liver; however, the enzymatic activity in peripheral blood leukocytes was in the low normal range. The child's mother had normal enzymatic activity in leukocytes but heterozygote levels in skin fibroblasts.
A new family with fra(10)(q25): Spontaneous expression and 100% expression with 100 μM BrdU
Authors: Gollin Susanne M. , Bock Hans‐Georg O. , Caskey C. Thomas , Ledbetter David H. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a family with fra(10)(q25) ascertained through a female with multiple minor anomalies and present in her phenotypically normal father and other family members. The site is expressed spontaneously at levels of 9% in lymphocytes, 2% in lymphoblasts, and 6% in skin fibroblasts. Expression frequency is significantly enhanced to levels as high as 100% by addition of BrdU to the culture medium. The consistently high level of induced expression in lymphoblasts from the proband facilitates analysis of the biochemical and structural bases of fragile site expression.
The Pena‐Shokeir syndrome: Report of nine Dutch cases
Authors: Lindhout D. , Hageman G. , Beemer F. A. , Ippel P. F. , Breslau‐Siderius L. , Willemse J. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on nine individuals with the Pena‐Shokeir syndrome. Clinical findings are compared with data on patients from the literature. Emphasis is made on genetic background, neuropathological findings, and (in two cases) on prenatal data. Possible pathogenetic mechanisms are discussed.
Antifolate‐induced misincorporation of deoxyuridine monophosphate into DNA by cells from patients with the fragile X syndrome
Authors: Wang Jin‐Chen C. , Beardsley G. Peter , Erbe Richard W. , Opitz John M. , Reynolds James F.
Published: June 2005

The fragile site at Xq27 is expressed in vitro under conditions that lead to decreased intracellular thymidine triphosphate concentration, a condition which has also been shown to promote the misincorporation into DNA of deoxyuridine monophosphate (dUMP) in place of thymidine. We tested for increased whole‐cell misincorporation of dUMP as a possible molecular mechanism for the expression of the fragile X abnormality. Neither deoxyuridine triphosphatase nor uracil‐DNA‐glycosylase, the two enzymes that normally prevent the accumulation of dUMP in DNA, was deficient in fragile X syndrome cells. Misincorporation of dUMP occurred in comparably low levels in both normal and fragile X syndrome lymphoblasts. Although these results provide strong evidence against generalized misincorporation of dUMP in fragile X syndrome cells, a substantial real difference present at Xq27 might not be detected in these studies of whole cells containing the diploid chromosome complement.
A premutation that generates a defect at crossing over explains the inheritance of fragile X mental retardation
Authors: Pembrey M. E. , Winter R. M. , Davies K. E. , Opitz John M. , Reynolds James F.
Published: June 2005

The view that the Martin‐Bell syndrome (X‐linked mental retardation with fragile site at Xq27/8) is inherited in a regular X‐linked fashion is becoming untenable with the increasing number of reports of transmission through phenotypically normal males. Analysis of the published pedigrees containing such males shows that their heterozygous daughters are never mentally retarded, and have either no fragile site or very few indeed. By contrast, in the next generation, a third of the female heterozygotes are mentally subnormal with an average of 29% fragile sites. These data suggest a premutation that generates the definitive mutation only when transmitted by a female. We propose an inherited sub‐microscopic chromosome rearrangement involving the Xq27/8 region that causes no ill effect per se, but generates a significant genetic imbalance when involved in a recombination event with the other X chromosome. This hypothesis explains many of the puzzling genetic aspects of the Martin‐Bell syndrome, but it also complicates the interpretation of linkage analysis with genetic markers.
Vascular abnormalities in a fetus with multiple pterygia
Authors: Fitch Naomi , Rochon Louise , Srolovitz Herbert , Hamilton Emily , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a 16‐week fetus with a lethal multiple pterygium syndrome and hydrops. No bony abnormalities were noted on radiographic or anatomical examination. A prominent meshwork of dilated, thin‐walled vessels was present in the subcutis over the entire body. This abnormal vascularity may have caused pterygium formation and death of the fetus.
The inheritance of spontaneous amyloidosis development in mice: A model for hereditary threshold metabolic disorders
Authors: Chai C. K. , Lerner Charles , Prieur David J.
Published: June 2005

To study the inheritance of spontaneous amyloidosis development in mice, we crossed the LLC strain (with a high incidence) with the A/J strain (with a low incidence) and with the HLC strain (with a zero incidence of amyloidosis). We produced the F1 and a backcross generation to each parental strain in each cross. Examination of the spleen, liver, and kidneys of each mouse for the presence of amyloid was made between age 15 and 18 months. The data fit neither a dominant nor a recessive single gene hypothesis for the development of amyloidosis. In consideration of amyloidosis as a hereditary threshold character, we developed an additive gene model. Subsequently, a test for fitness of the observed percentages to the expected percentages in the backcross generations was made according to this model. The observed percentages of amyloidosis in the spleens, livers, and individual mice agreed with the expected percentages in the LLC × A/J crosses but not in the LLC × HLC crosses. Therefore, we conclude that for the development of amyloidosis, a difference exists at one locus between LLC and A/J and at more than one locus between LLC and HLC. The probability of development of amyloidosis in an individual depends on the effects of the genes at these loci. For hereditary metabolic disorders that cannot be explained by either a single dominant or recessive gene hypothesis, this genetic model may be useful to test whether the development of the disease is due to additive effects of genes.
Deficiency of chromosome 8p21.1→8pter: Case report and review of the literature
Authors: Dobyns William B. , Dewald Gordon W. , Carlson Richard O. , Mair Douglas D. , Michels Virginia V. , Opitz John M. , Reynolds James F.
Published: June 2005

The clinical manifestations and cytogenetic changes of a patient with 46,XY,del(8)(p21.1) are compared with those of nine other patients with a similar deficiency of chromosome 8. Patients with this chromosome anomaly have a syndrome of postnatal growth retardation, microcephaly, mental retardation, epicanthal folds, posteriorly angulated and malformed ears, short neck, relatively increased internipple distance, and congenital heart defect. A short and broad nose, a wide and flat nasal bridge, and a small jaw are observed in young patients but tend to become less apparent with increasing age. In most instances, the syndrome has been associated with a de novo chromosome abnormality. Levels of glutathione reductase in our patient were normal—a finding consistent with localization of the gene coding for this enzyme to the proximal part of band 8p21.1 if gene dosage studies are reliable.
Facioscapulohumeral dystrophy with cochlear hearing loss and tortuosity of retinal vessels
Authors: Gieron Maria A. , Korthals Jan K. , Kousseff Boris G. , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a mother and her three children with facioscapulohumeral dystrophy (FSHD), sensorineural hearing loss, and marked tortuosity of the retinal vessels. Initially the children presented with speech difficulties and hearing deficit. Hearing loss ranged from mild to severe. An audiologic evaluation, including brain stem auditory evoked responses in all patients, indicated a cochlear origin of hearing loss and intact pathways from the cochlea to the temporal lobe. The association of FSHD with hearing loss and tortuosity of the retinal vessels suggests previously unrecognized pleiotropy of FSHD (McKusick 15890) or a “new” type of FSHD.
Muscular dystrophy in Saskatchewan Hutterites
Authors: Shokeir M. H. K. , Rozdilsky B. , Opitz John M. , Reynolds James F.
Published: June 2005

A slowly progressive form of muscular dystrophy was studied in a Dariusleut Hutterite kindred from a colony in west‐central Saskatchewan. The disorder combines some characteristics of the dominantly inherited facio‐scapulo‐humeral and the recessively inherited limb‐girdle types of muscular dystrophy. Intellect, vision, hearing, and sensations were normally preserved. Nerve conduction was also intact.

The disorder reported herein resembles a type of muscular dystrophy we previously described in the Manitoba Schmiedeleut Hutterites [Shokeir and Kobrinsky, 1976]. This condition, which affects both sexes, appears to be genetic in origin and recessively inhertited.
Neurofibromatosis and fragile‐X syndrome in the same patient
Authors: Mitchell Joyce A. , Wray Jane , Michalski Karen , Opitz John M. , Reynolds James F.
Published: June 2005

We report on an 11 1/2‐year‐old boy with neurofibromatosis and the fragile‐X syndrome. Clinical manifestation of neurofibromatosis included multiple cafe‐au‐lait spots, axillary freckles, congenital glaucoma, relative macrocephaly, radiologic findings of overtubulation of the long bones, and precocious puberty. The fragile‐X syndrome manifests itself as mental retardation with behavior problems, macroorchidism, and specific cytogenetic findings. The boy has normal serum hormone levels, but a greatly elevated FSH on a first morning void, which contains the nocturnally secreted gonadotropins.

This seems to be the first reported occurrence of the fragile‐X syndrome with another inherited disease.
Familial recurrence of achondroplasia
Authors: Fitzsimmons J. S. , Opitz John M. , Reynolds James F.
Published: June 2005

A family is reported among whom 2 second‐cousins‐once removed (two half or half third cousins) demonstrate clinical and radiological features of classical achondroplasia.
Translocation mosaicism in a woman having multiple miscarriages
Authors: Sciorra Leonard J. , Lee Ming‐Liang , Cuccurullo Gail , Opitz John M. , Reynolds James F.
Published: June 2005

We concluded cytogenetic studies on a couple who had had several spontaneous abortions. The peripheral lymphocytes of the woman repeatedly showed a mosaic pattern with a structurally altered, apparently balanced, autosomal translocation between chromosomes 4 and 5. Various studies were reviewed and it was concluded that the true frequency of structural rearranged mosaics in recurrent pregnancy loss is not known.
A family with the Saethre‐Chotzen syndrome
Authors: Bianchi Elena , Aricǒ Maurizio , Podestǎ Alberto F. , Grana Marco , Fiori Paola , Beluffi Giampiero , Opitz John M. , Reynolds James F.
Published: June 2005

Acrocephalosyndactyly (ACS) is an inherited syndrome of premature synostosis of the cranial sutures and abnormalities in the distal segments of the limbs. Several forms of ACS have been described. ACS type III (or Saethre‐Chotzen syndrome) is characterized by microcephaly, skull asymmetry, mild syndactyly, and facial abnormalities. We describe an Italian family with ACS III in which two sibs are clearly affected; the mother and the maternal grandmother show some features of the syndrome.
The prenatal detection of the fragile X chromosome: Review of recent experience
Authors: Jenkins Edmund C. , Brown W. Ted , Wilson Miriam G. , Lin Ming S. , Alfi Omar S. , Wassman E. Robert , Brooks Judith , Duncan Charlotte J. , Masia Annette , Krawczun Michael S. , Opitz John M. , Reynolds James F.
Published: June 2005

The fragile X chromosome has been identified in specimens from 17 male and 10 female fetuses in 11 laboratories throughout the world, obtained from at least 79 fetuses at increased risk for the fra(X) syndrome. Of these, 19 were confirmed, 6 were pending, 1 was negative and 1 could not be confirmed. Twenty‐five of the 79 cases were studied in our laboratory (Institute for Basic Research [IBR]) and resulted in fra(X) demonstration in specimens from 3 male and 5 female fetuses. All 3 males and 2 of the 5 females have been confirmed. When aniocytes from a the two confirmed female fetuses were exposed to FUdR after culturing in Chang medium, fra(X) frequencies were virtually negative indicating that Chang medium should not be used in fragile X studies at least when FUdR is used to induce fragility. Finally, amniocytes from a fra(X) male fetus studied in 3 different laboratories exhibited strikingly different frequencies. To date, we have experienced no falsepositives or negatives, but the latter case was controversial. It is recommended that laboratories undertaking fra(X) prenatal detection use a combination of at least two different proven induction systems as well as complementary DNA marker studies to prevent false negative diagnosis.
Fragile X and autism: A multicenter survey
Authors: Brown W. Ted , Jenkins Edmund C. , Cohen Ira L. , Fisch Gene S. , Wolf‐Schein Enid G. , Gross Anne , Waterhouse Lynn , Fein Debra , Mason‐Brothers Ann , Ritvo Edward , Ruttenberg Bertram A. , Bentley William , Castells Salvador , Opitz John M. , Reynolds James F.
Published: June 2005

We screented 183 autistic males for the fra(X) and found 24 (13.1%) to be positive. Adding the subjects of this study to those of 11 other surveys, of which 6 were positive and 5 were negative, a total of 614 autistis males have been screened. Overall 47 (7.7%) were positive. Based on this estimate and the prevalence of autism and fra(X), we estimate that 12.3% of fra(X) males are autistic. We have found that 17.3% of our fra(X) males were autistic and overall a 21.2% frequency has been reported, these higher figures are most likely due to biases in age and ascertainment. With an overall 7.7% frequency of fra(X) among autistic males and an estimated 12.3% of autism among fra(X) males, we conclude there is likely to be a significant association of fra(X) with autism. Because fra(X) appears to be the single most common cause of the condition, chromosomal testing is recommended for any autistic person with undiagnosed etiology.
Infantile autism: An occasional manifestation of fragile (X) mental retardation
Authors: McGillivray Barbara C. , Herbst Diana S. , Dill Frederick J. , Sandercock H. Joyce , Tischler Bluma , Opitz John M. , Reynolds James F.
Published: June 2005

Classical infantile autism occurs more frequently in males and has recently been noted in patients with the fragile (X) form of X‐linked mental retardation (XLMR). In order to better understand this association and to determine whether fra(X) XLMR could account for the excess of autistic males, we investigated a group of institutionalized severely handicapped adults, 33 males and eight females, who were diagnosed as autistic using the DSM III diagnostic criteria of infantile autism. Chromosome studies using FUdR showed that three of the males had the Xq27 fragile site. We confirmed the association of autism and fra(X) XLMR, and showed that this extreme form of behaviour is part of the spectrum seen in the Martin‐Bell syndrome. Two of the three autistic males with the Xq27 fragile site had ahistory of birth insults, which in combination with developmental deficits due to the fragile X gene, might have led to the behavioural disorder. Even though the fragile X cannot account for the excess of males with classical autism, it is an important X‐linked factor in its cause. The diagnosis can allow more accurate counselling for this subset of autistic males.
Autism in fragile X females
Authors: Hagerman Randi J. , Chudley Albert E. , Knoll Joan H. , Jackson Alfred W. , Kemper Melinda , Ahmad Razia , Opitz John M. , Reynolds James F.
Published: June 2005

We present two women with the fragile X syndrome (Martin‐Bell syndrome) and autism. Both are mentally retarded, one mildly and one severely. Cytogenetic studies showed a high percentage of lymphocytes with the fragile X chromosome and inactivation occurring preferentially in the normal X chromosome.

Autism is shown to be a severe behavioral and cognitive manifestation of the fragile X syndrome in females.
Fra(2) (q13) and inv(9) (pllq12) in autism: Causal relationship?
Authors: Jayakar Parul , Chudley Albert E. , Ray Mano , Evans Jane A. , Perlov Jack , Wand Rox , Opitz John M. , Reynolds James F.
Published: June 2005

Twenty individuals with autism or related disorders underwent chromosome analysis and physical examinations with documentation of minor anomalies. Chromosome anomalies were identified in 3: 2 had the heritable folate sensitive fra (2) (q13) site and 1 had an inv (9) (p11q12). No heritable chromosome variants or anomalies were seen in 20 age and sex‐matched control individuals. When patients with the fra (2) were excluded from analyses, there was no difference in the frequency of chromosome breaks and/or gaps between the study group and control group. The results of this study suggest that heritable folate sensitive fragile sites and other chromosome variants may be more commonly seen in individuals with autism or related disorders in childhood than in the general population.
Psychiatric disability associated with the fragile X chromosome
Authors: Reiss A. L. , Feinstein C. , Goldsmith K. E. Toomey B. , Rosenbaum K. , Caruso M. A. , Opitz John M. , Reynolds James F.
Published: June 2005

Fragile X (or Martin‐Bell) syndrome, a common, genetic, mental retardation disorder is increasingly being recognized as a major cause of cognitive disability and psychiatric illness in boys. Here, we present a study in which relatives in 4 generations of a large family with the fra(X) chromosome were given comprehensive psychiatric evaluations in order to further describe the psychopathology associated with this condition. Three of 4 males with the fra(X) chromosome were found to have autistic behavior. An adult fra(X) male had a chronic schizoaffective disorder and mental retardation. In femal relatives, a relationship was found between the fra(X) carrier status and psychopathology including schizoaffective and major affective disorders.
The fragile(X) syndrome: The mutation problem
Authors: Jacobs Patricia A. , Sherman Stephanie , Turner Gillian , Webb Tessa , Opitz John M. , Reynolds James F.
Published: June 2005

In an attempt to understand the nature of the mutational event leading to the fra(X) syndrome, we have searched for sporadic cases in 3 populations: affected males, affected females, and non‐affected transmitting females. In all 3 populations there was a dearth of isolated cases, and the reasons for this are discussed.
Trisomy 22 mosaicism syndrome and Ullrich‐Turner stigmata
Authors: Wertelecki W. , Breg W. R. , Graham J. M. , Iinuma K. , Puck S. M. , Sergovich F. R. , Opitz John M. , Reynolds James F.
Published: June 2005

Mosaic trisomy 22, ascertained in three unrelated patients, was found to be associated with body asymmetry and signs of the Ullrich‐Turner syndrome including short stature, ptosis, webbed neck, nevi, cubitus valgus, dysplastic nails, malformed greatvessels, and abnormal ovaries. These anomalies in trisomy 22 mosaicism have not been emphasized heretofore. In each of our patients, trisomy 22 mosaicism was found only in fibroblasts. In one patient, the trisomy resulted from a paternal first meiotic nondisjunction, and in the 46,XX cells, both chromosomes 22 were of paternal origin.
A new skeletal dysplasia syndrome with dwarfism, craniofacial anomalies, and unique radiographic findings
Authors: Jones Kenneth Lee , Jones Kenneth Lyons , Miller Kenneth , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a boy from a consanguinous marriage who has a unique skeletal dysplasia, marked dwarfism, mild developmental delay, eye abnormalities, and cranofacial and skeletal changes that have not been described previously.
Three new cases of Tel Hashomer camptodactyly syndrome in one Arabic family
Authors: Tylki‐Szymanska Anna , Opitz John M. , Reynolds James F.
Published: June 2005

Three new cases with the Tel Hashomer camptodactyly syndrome have been ascertained in an Arabic family. This report emphasizes some of the manifestations seen in these three relatives. The Tel Hashomer captodactyly syndrome is thought to be a connective tissue disorder of unknown basic defect.
A balanced de novo X/autosome translocation in a girl with manifestations of lowe syndrome
Authors: Hodgson S. V. , Heckmatt J. Z. , Hughes E. , Crolla J. A. , Dubowitz V. , Bobrow M. , Opitz John M. , Reynolds James F.
Published: June 2005

The Oculo‐cerebro‐renal syndrome of Lowe is an X‐linked recessive disorder characterised by mental and growth retardation, renal rickets with renal tubular acidosis, generalised aminoaciduria, hypotonia, cataracts, glaucoma and frontal bossing. Manifestations of this syndrome were seen in a girl with no family history of the disorder, but who was found to have a de novo balanced X/3 translocation, with a breakpoint at Xq25. She had also inherited a balanced 14/17 translocation from her father. It is postulated that the clinical picture may be the result of disruption of the X chromosome within the gene at the locus for Lowe syndrome, with non‐random inactivation of the normal X, which may permit the expression of this X‐linked recessive disorder in a girl.
Growth hormone deficiency in the Rothmund‐Thomson syndrome
Authors: Kaufmann Silvia , Jones Marilyn , Culler Floyd L. , Jones Kenneth Lee , Opitz John M. , Reynolds James F.
Published: June 2005

We describe the first proven occurrence of growth hormone deficiency in an individual with the Rothmund‐Thomson syndrome. This was suspected because of the patient's severely retarded growth and bone age and her failure to respond normally to growth hormone stimulation testing with I‐DOPA, arginine, and growth hormone releasing factor. In addition, we have briefly reviewed other genetic and malformation syndromes that have been found associated with growth hormone deficiency. We recommend that growth hormone deficiency be considered in these syndromes, especially when the growth failure is more marked than expected.
The Perlman familial nephroblastomatosis syndrome
Authors: Greenberg Frank , Stein Fernando , Gresik Mary V. , Finegold Milton J. , Carpenter Robert J. , Riccardi Vincent M. , Beaudet Arthur L. , Opitz John M. , Reynolds James F.
Published: June 2005

In 1973, Perlman et al described a familial syndrome of bilateral renal hamartomas with or without nephroblastomatosis, macrosomia, islet cell hypertrophy, unusual facies, and early lethality. Two additional sibs were recently reported by Neri et al [1984]. We report on two sibs with polyhydramnios, fetal ascites, and abdominal muscular hypoplasia, visceromegaly, and subsequent development of Wilms tumor in one of them. Delineated features of this syndrome include visceromegaly, macrosomia, renal hamartomas, nephroblastomatosis, cryptorchidism in males, unusual facial appearance, polyhydramnios, fetal ascites, and Wilms tumor but do not include hemihypertrophy, omphalocele or umbilical abnormalities, aniridia, or other conditions known to be associated with wilms tumor. This condition should be considered primarily in the differential diagnosis of fetal ascites without hydrops and possibly in the differential diagnosis of familial Wilms tumor, polyhydramnios, congenital hepatomegaly, or nephromegaly.
A new syndrome of severe upper limb hypoplasia and Müllerian duct anomalies
Authors: Halal Fahed , Opitz John M. , Reynolds James F.
Published: June 2005

We report on the occurrence of a new syndrome of upper limb hypoplasia and Müllerian duct anomalies in a French Canadian family. Limb/acral anomalies varied in expression from postaxial polydactyly to ectrodactyly to severe upper limb hypoplasia with split hand. Genital anomalies varied in expression from only a vaginal septum to complete duplication of uterus and vagina in the female to a micropenis in one of two affected males. The syndrome appears to be inherited as an autosomal dominant trait.
Brief clinical report: A genetic association between microcephaly and lymphedema
Authors: Crowe Carol A. , Dickerman Lois H. , Opitz John M. , Reynolds James F.
Published: June 2005

We discuss a family in which microcephaly and lymphedema are co‐segregating as an apparently autosomal or X‐linked dominant trait. A review of each malformation is presented with reference to the known genetic patterns of each. This combination of microcephaly and lymphedema may be a unique syndrome, previously undescribed because of subtleties of expression in affected individuals.
Congenital aplasia of the extensor muscles of the fingers and thumb associated with generalized polyneuropathy: An autosomal recessive trait
Authors: Hamanishi Chiaki , Ueba Yasuo , Tsuji Takeo , Ijiri Shinichiro , Mihara Taku , Yamanaka Kiyoshi , Yamamuro Takao , Reynolds James F.
Published: June 2005

Three sibs born to normal but consanguinous parents had flexion deformities of the thumb and fingers on one hand and sensory deficit in the other hand. Extensor muscles were absent or vestigial in all of them. Polyneuropathic electrophysiological findings were detected in 4 limbs. This is an apparently autosomal recessive trait previously unreported.
Cyclopia as a result of an unbalanced familial translocation, rcp(7;18)(q34;q21)
Authors: Smart Ronald D. , Ross Judy , Amann Gabriel , Nelson Matilda M. , Reynolds James F.
Published: June 2005

One fetus is described with cyclopia and associated abnormalities as a result of an unbalanced translocation involving chromosomes 7 and 18 [46XX, del 7, rcp(7;18)(q34;21)]. The parents had had a previous infant described as having possible holoprosencephaly, but no medical records were available to substantiate this description.
Keutel syndrome: Clinical report and literature review
Authors: Cormode Edward J. , Dawson Malcolm , Lowry R. Brian , Opitz John M. , Reynolds James F.
Published: June 2005

In 1972 Keutel et al described a brother and sister with brachytelephalangism, hearing loss, peripheral pulmonary stenosis and abnormal cartilage calcification. Since then, three additional cases have been reported. We report a sixth case and discuss the clinical findings and cause.
Prevalence of mitral‐valve prolapse in the Stickler syndrome
Authors: Liberfarb Ruth M. , Goldblatt Allan , Opitz John M. , Reynolds James F.
Published: June 2005

An increased prevalence of mitral‐valve prolapse occurs in several connective tissue dysplasias, including Marfan syndrome, Ehlers‐Danlos syndrome, and pseudoxanthoma elasticum. We evaluated 57 patients diagnosed as having the Stickler syndrome for mitral‐valve prolapse by ausculation and two‐dimensional echocardiography. The diagnosis was made on the basis of craniofacial and musculoskeletal abnormalities, sensorineural hearing loss, eye defects, and a family history of Stickler syndrome. Twenty‐six patients (45.6%) had mitral‐valve prolapse, including 11 of 22 females (50.0%) and 15 of 35 males (42.9%). The age range of our study population was 4 to 60 years. Prevalence of mitral‐valve prolapse did not increase with age. Nine patients (34.6% of those with mitral‐valve prolapse) had the click‐murmur syndrome; only one of them was symptomatic.

Because of the growing list of complications associated with mitral‐valve prolapse, all patients with Stickler syndrome should be evaluated by auscultation, electrocardiogram, and echocardiography. Those with mitral‐valve prolapse should be advised to have periodic follow‐up and to instruct physicians caring for them of their need for antibiotic prophylaxis with certain surgical procedures.
Lethal osteogenesis imperfecta with amniotic band lesions: Collagen studies
Authors: van der Rest M. , Hayes A. , Marie P. , Desbarats M. , Kaplan P. , Glorieux F. H. , Opitz John M. , Reynolds James F.
Published: June 2005

An infant was born with osteogenesis imperfecta (OI) and died after 7 days. In addition, there were amniotic constriction bands and amputations of several digits of the upper and lower limbs. The radiologic picture was suggestive of type III OI. Histomorphometric analysis of the bone showed a trabecular bone volume of 15.1% compared to 26.9% for age‐matched controls. This was due to a decreased apposition of matrix by the osteoblasts. Because abnormal collagen synthesis has been suggested as the underlying defect in most forms of OI, collagen studies were undertaken using intact tissues.

Bone and skin collagen solubilities were strikingly reduced. Shortened type I collagen molecules, representing 25% of the total type I collagen, were produced by pepsin digestion of the demineralized bone matrix. The molecular weight of the shortened collagen, was 10 kd lower than normal for both the α1 and α2 chains as determined by gel electrophoresis. The bone acetic acid‐soluble collagen showed few shotened α‐chains. Twenty‐five percent of the acid‐soluble bone collagen was cleaved into shortened molecules by a pepsin digestion. The shortened α1 chain was purified by high‐performance liquid chromatography (HPLC).
Mendelian inheritance of isolated nonsyndromic cleft palate
Authors: Rollnick Beverly R. , Kaye Celia I. , Opitz John M. , Reynolds James F.
Published: June 2005

Isolated, apparently nonsyndromic cleft palate (CP) is thought to be etiologically heterogeneous. The multifactorial threshold explanation for CP is postulated in most cases. Mendelian inheritance has been documented in 3 families. We report on three unrelated white families with 17 relatives in several generations affected with CP, including submucous CP and bifid/absent uvula. We could find no evidence of a cleft syndrome. In one family, the pattern is consistent with autosomal dominant inheritance. In 2 families, the pattern is consistent with X‐linked recessive inheritance. The specific findings and their implications for family evaluation and genetic counseling are discussed.
Characteristic craniofacial appearance and brachytelephalangy in a mother and son with Kallman syndrome in the son
Authors: Hunter Alasdair G. W. , Feldman William , Miller Jonathan , Reynolds James F.
Published: June 2005

We report on a mother and son with a similar facies characterized by a square forehead, small nose, telecanthus, and this upper lip. They both had a similar metacarpal‐phalangeal profile characterized by marked brachytelephalangy. They were both short in comparison to other family members, and the son had hypogonadotropic‐hypogonadism and anosmia. We favor the hypothesis of a single autosomal dominant gene with variable expression of the hypogonadism and anosmia, although there are alternative explanations for the combination.
Male pseudohermaphroditism, partial androgen receptors defect, 11p13 deletion: Indication of gene localization
Authors: Malpuech Georges , Sultan Charles , Bertheas Marie‐Francoise , Loire Corinne , Renaud Hubert , Francannet Christine , Vanlieferinghen Philippe , Opitz John M. , Reynolds James F.
Published: June 2005

A partial androgen receptor defect was found in a boy with male pseudohermaphroditism and an 11p13 deletion. We hypothesize that a gene responsible for the function or structure of androgen receptors might be localized in the 11p13 band or in close proximity to it.
Reduced plasma haptoglobin and urinary taurine in familial seizures identified through the multisib strategy
Authors: Haines Jonathan L. , Panter S. Scott , Rich Stephen S. , Eaton John W. , Tsai Michael Y. , Anderson V. Elving , Opitz John M. , Reynolds James F.
Published: June 2005

The multisib (MS) sampling strategy was used for detecting possible genetic influences on a complex and heterogeneous disorder. The MS strategy increases the likelihood of selecting pedigrees for single genetic factors and allows the efficient analysis of data. The collection of complete pedigrees will procure additional data, but at a large marginal expense. The MS ascertainment procedure was applied to seizure disorders by examination of taurine excretion levels and by conducting two‐dimensional gel electrophoresis of plasma proteins. Reduced taurine excretion (proposed to be genetically controlled) was found to associate with seizures, particularly in those individuals with a generalized spike and wave (GSW) EEG, or in families with a GSW‐seizure history. Examination of two‐dimensional gels showed hypohaptoglobinemia in several seizure patients [Panter et al, 1984]. The frequency of hypohaptoglobinemia is greatly increased in familial seizure cases, and may also be genetically controlled. Thus the MS strategy has proven successful in identifying kindreds in which specific physiological alterations may contribute toward the complex phenotype of seizures.
A new category of lethal short‐limbed dwarfism
Authors: Knowles Simon , Winter Robin , Rimoin David , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a first cousin marriage between Asians which resulted in 13 pregnancies; 4 of the offspring were normal, 5 were stillborn dwarves, 3 pregnancies resulted in miscarriage, and one was terminated for dwarfism detected prenatally. The radiology and histology are unique and the predigree suggests autosomal recessive inheritance.
A distinct lethal neonatal chondrodysplasia with snail‐like pelvis: Schneckenbecken dysplasia
Authors: Borochowitz Z. , Jones K. L. , Silbey R. , Adomian G. , Lachman R. , Rimoin D. L. , Opitz John M. , Reynolds James F.
Published: June 2005

We describe the clinical, radiographic, histopathologic, and ultrastructural features of a distinct neonatal lethal chondrodysplasia inherited as an autosomal recessive trait. The characteristic radiographic findings consist of flattened, hypoplastic vertebral bodies; short ribs; hypoplastic iliac bones with “a snail‐like” configuration; short, broad long‐bones with dumbbell‐like appearance; short and wide fibula; and precocious ossification of the tarsus. Chondro‐osseous histology is characteristic with hypervascularity, increased cellular density, and normal size chondrocytes with a centrally located round nucleus and absence of lacunar space. Because of the snail‐like radiographic appearance of the pelvis in this disorder, we propose the name “Schneckenbecken dysplasia” (ie, German for snail pelvis).
Prenatal ultrasonographic features of the Pena–Shokeir I syndrome and the trisomy 18 syndrome
Authors: Muller Linnie M. , de Jong Greetje , Reynolds James F.
Published: June 2005

The prenatal ultrasonographic features found in two cases each of the Pena‐Shokeir I and the trisomy 18 syndromes are described. All four cases were referred for ultrasonographic evaluation of polyhydramnios, clinically detected in the third trimester. A detailed ultrasonographic study of the craniofacial structures, intrathoracic organs, and limbs showed scalp edema, multiple ankyloses, camptodactyly, rocker‐bottom feet, cardiac arrhythmias, and lung hypoplasia. Chromosome analysis showed trisomy 18 in two cases; in the other two cases the diagnosis of the Pena–Shokeir I was confirmed after delivery. The similarity of the two syndromes with respect to ultrasound findings is discussed.
Psychological response to amniocentesis: II. Effects of coping style
Authors: Phipps Sean , Zinn Arthur B. , Opitz John M. , Reynolds James F.
Published: June 2005

Differences in coping style were assessed in a group of women undergoing amniocentesis and a control group not having the procedure. Subjects were divided into two groups according to coping style; “monitors” (information seekers) and “blunters” (information avoiders). In the amniocentesis group, coping style was associated with differences in mood state and change in mood state over time. “Monitors” experienced greater mood disturbance than “blunters” both before and during the procedure, but this effect disappeared after communication of amniocentesis results. Coping style was nor associated with differences in maternal attitudes toward pregnancy or maternal‐fetal attachment. In the control group, there were no differences between “monitors” and “blunters” on any of the mood state or pregnancy measures. Implications of these findings for providers of genetics services are discussed.
Abdominal distension in Kaufman‐McKusick syndrome
Authors: Farrell S. A. , Davidson R. G. , DeMaria J. E. , Grant L. , Toi A. , Opitz John M. , Reynolds James F.
Published: June 2005

A female infant with Kaufman‐McKusick syndrome redeveloped respiratory distress and abdominal distention at 5 weeks of age. Ultrasonography demonstrated recurrence of peritoneal cysts and hydrometrocolpos. It is postulated that refluxing vaginal secretions may contribute to the abdominal distention seen in many infants with Kaufman‐McKusick syndrome.
Interstitial 7q deletion [46,XY,del (7) (pter → cen::q112 → qter)] in a retarded quadriplegic boy with normal beta glucuronidase
Authors: Frydman Moshe , Steinberger Julia , Shabtai Fiorella , Steinherz Reuben , Opitz John M. , Reynolds James F.
Published: June 2005

A 14‐year‐old severely retarded male with deletion of chromosomal band 7 cen → q112 is described.

Clinical features include short stature, microcephaly, unusual facies with narrow forehead, short nose, malar hypoplasia, protruding alveolar ridges and incisors, receding chin, relatively long philtrum, and large ears. In addition, he had bilateral inguinal herniae cryptorchidism with hypogonadism, pulmonic stenosis, and spastic quadriplegia.

Normal activity of beta‐glucuronidase was found in the patient's leukocytes. This finding suggests that the gene is not in the deleted region, narrowing the smallest region of overlap to 7q112 → q22.
An unusal case of ectodermal dysplasia
Authors: Cortes Fanny , Lacassie Yves , Fraser F. Clarke , Preus Marilyn
Published: June 2005

The syndrome was characterized by striking hypoplasia of nails, malformations of hands and feet, curly hair, small lower teeth and seizures. There were no similarly affected relatives. Death occurred at 31 months with the patient apparently in status epilepticus with terminal hepatorenal syndrome.
Long survival in a 69,XXY triploid male
Authors: Sherard J. , Bean Charles , Bove Betsy , DelDuca Vincent , Esterly K. L. , Karcsh Henry J. , Munshi Gaurang , Reamer James F. , Suazo Gloria , Wilmoth Donna , Dahlke Mariam B. , Weiss Carol , Borgaonkar Digamber S. , Reynolds James F.
Published: June 2005

We report on an infant with a 69,XXY chromosone constitution who survived for 10½ months; this is the longest survival reported with this condition to date. The infrequency of this disorder, data on natural history, and improved survival, possibly due to better management of respiratory illness and prematurity, are all factors worth noting in counseling on such rare conditions. Genotyping demonstrated the extra genome to be of maternal origin.
Balanced double complex translocations [46,XX,t(1p;6p;7p;3q;11p)(11q;22p;21q)] in an infant with multiple congenital anomalies
Authors: Fukushima Yoshimitsu , Kuroki Yoshikazu , Ito Taizo , Opitz John M. , Reynolds James F.
Published: June 2005

We describe a 1‐month‐old female infant with balanced double complex translocations [46,XX,t(1p;6p;7p;3q;11p) (11q;22p;21q)]. She had a multiple congenital anomalies syndrome of microcephaly, unilateral corneal staphyloma, hypoplastic thumbs, ectrodactyly of the right foot, brachydactyly of the left third toe, and syndactyly between the left fourth and the fifth toes. The complex chromosome rearrangements of the patient involve 8 breakpoints, the greatest number of breakpoints in complex chromosome rearrangements of humans known to us. The 8 breakpoints are 1p22, 3q27, 6p21, 7pl5, 1lp15, 11q11, 21q11, and 22p11. These are not related to any confirmed fragile sites. These double complex translocations seemed to have occurred de novo.
Neural tube defects in spontaneous abortions
Authors: Byrne Julianne , Warburton Dorothy , Opitz John M. , Reynolds James F.
Published: June 2005

Nine specimens with neural tube defects (NTDs) were ascertained in a consecutive series of spontaneous abortions in New York City, giving a rate of 10.2 per 1,000 testable embryos and fetuses. All seven successfully karyotyped abortions had a chromosome anomaly. The rate of NTDs in miscarriages in New York is only one‐third the rate in miscarriages in London, and the difference is due entirely to a deficit of fetuses with normal chromosomes. Our data, together with data from three other centers, indicate that there is a strongly positive association (r = 0.96) between rates of neural tube defects in early pregnancy and at term. The implications of these findings for genetic counseling and for etiologic studies are discussed.
New multiple congenital anomalies/mental retardation syndrome with cardio‐facio‐cutaneous involvement—the CFC syndrome
Authors: Reynolds James F. , Neri Giovanni , Herrmann Jurgen P. , Blumberg Bruce , Coldwell James G. , Miles Paul V. , Opitz John M. , Carey John C.
Published: June 2005

Eight patients (4 males, 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which was designated the Cardio‐Facio‐Cutaneous (CFC) syndrome and which includes congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure. Cardiac defects were variable, the most common being pulmonic stenosis and atrial septal defect. Typical facial characteristics were high forehead with bitemporal constriction, hypoplasia of supraorbital ridges, antimongoloid slant of palpebral fissures, depressed bridge of nose, and posteriorly angulated ears with prominent helices. The hair was usually sparse and friable. Skin changes varied from patchy hyperkeratosis to a severe generalized ichthyosis‐like condition. All cases were sporadic in occurrence, there was no family history of consanguinity, and chromosomes were normal. Although presumed to be genetic, the cause of the CFC syndrome remains unknown.
Cherubism, gingival fibromatosis, epilepsy, and mental deficiency (Ramon syndrome) with juvenile rheumatoid arthritis
Authors: Pina‐Neto João M. , Moreno Aparecida Fátima C. , Silva Luis Roberto , Velludo Maria Angeles S. L. , Petean Eucia Beatriz L. , Ribeiro Maria Valeriana M. , Athayde‐Junior Luis , Voltarelli Júlio Cesar , Opitz John M. , Reynolds James F.
Published: June 2005

This is a report on four persons in one family with a condition similar to that described by Ramon et al [Oral Surg 24:436–48, 1967] in two sibs born to a consanguineous couple. Our patients also had mental deficiency, epilepsy, cherubism due to fibrous dysplasia of the maxillae, gingival fibromatosis, hypertrichosis, and stunted growth. This appears to be an autosomal recessive trait in both families. Our patients are the second set reported with this syndrome; they also have juvenile rheumatoid arthritis, which was not described in the family reported by Ramon et al [Oral Surg 24:436–48, 1967]. We conclude that the Ramon syndrome should also include juvenile rheumatoid arthritis.
Deletion of proximal 6q: A clinical report and review of the literature
Authors: Yamamoto Yoshifumi , Okamoto Noriko , Shiraishi Hirohiko , Yanagisawa Masayoshi , Kamoshita Shigehiko , Opitz John M. , Reynolds James F.
Published: June 2005

We report on a 13‐year‐old boy who had an interstitial deletion of the long arm of chromosome 6[46,XY,del(6)(pter→ql3::ql5→qter)]. A characteristic facial appearance with facial asymmetry, vertebral anomalies, valgus heels with flat feet, and congenital heart defect seem to form part of a specific del 6q syndrome.