bluuebunny/crossref_metadata_2025 huggingface dataset:
The neurofaciodigitorenal (NFDR) syndrome
Authors: Freire‐Maia Newton , Pinheiro Marta , Opitz John M. , Herrmann Jürgen
Published: June 2005

We describe in two brothers a previously apparently unreported multiple congenital anomalies/mental retardation (MCA/MR) syndrome of high, prominent forehead, vertical groove on tip of nose, “cowlick,” ear anomalies, acrorenal field defect (incipient unilateral triphalangism, broad halluces, with unilateral renal agenesis in one of the boys), megalencephaly associated with congenital hypotonia, severe mental retardation and highly abnormal EEG without seizures, intrauterine growth retardation and primordial shortness of stature in one brother. This is a Group III (“provisionally private”) MCA/MR syndrome and presumed to be due to a Mendelian (either X‐linked or autosomal recessive) mutation. We do not think these patients have the FG syndrome. The condition has been named the neurofaciodigitorenal (NFDR) syndrome.
Bilateral branchial cleft sinuses associated with intrauterine and postnatal growth retardation, premature aging, and unusual facial appearance: A new syndrome with dominant transmission
Authors: Lee W. K. , Root A. W. , Fenske N. , Opitz John M.
Published: June 2005

A mother and son with bilateral branchial sinuses, intrauterine and postnatal growth retardation, unusual facial appearance, and premature aging in the mother are reported. No other members of the family are similarly affected. No hormonal or systemic cause of growth retardation was identified. Chromosomal studies with G‐banding were normal. It is suggested that this syndrome is a dominant trait, the mother being the initial mutant.
Collagen synthesis by duchenne myogenic clones: Pathogenic implications for the disease
Authors: Ionasescu V. , Ionasescu R. , Massimini G. , Sandra A. , Opitz John M.
Published: June 2005

Myogenic cell clones were grown in triplicates from a 3‐year‐old boy with Duchenne muscular dystrophy and three normal control boys matched for age. The well‐differentiated Duchenne myogenic clone had lower creatine kinase activity and lower MM isozyme than the control clones. Analysis of (3H)‐proline incorporation demonstrated a 2.2‐fold increase in (3H)‐hydroxyproline released into the medium of Duchenne myogenic cell clones, whereas intracellular (3H)‐hydroxyproline levels showed normal values. These results strongly suggest that the increased amount of collagen present in Duchenne dystrophic muscle is related to the primary defect of the disease and is not due to a secondary replacement fibrosis.
Upper limb involvement in the Klein‐Waardenburg syndrome
Authors: Goodman Richard M. , Lewithal Ilana , Solomon Albert , Klein David , Optiz John M.
Published: June 2005

Upper limb involvement in the Klein‐Waardenburg (K‐W) syndrome is documented in two affected sibs and in four other previously reported patients. In addition to the key facial and auditory findings observed in the Waardenburg syndrome type I, these patients have such bilateral upper limb defects as hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, and syndactyly. The cause of the K‐W syndrome is not known although there is some evidence for autosomal dominant inheritance, but further documentation is needed before this can be considered conclusive.
Graves disease in a patient with the del(18p) syndrome
Authors: Jones Kenneth Lee , Carey Dennis E. , Opitz John M.
Published: June 2005

We report the first known patient with a del(18p) and Graves disease. This deletion has previously been reported to be associated with autoimmune thyroid disease and, perhaps, with inborn errors of thyroxin biosynthesis. We present the clinical and histological information on this patient and review the literature in an attempt to clarify the relationship between abnormalities of chromosome 18 and thyroid disease.
Genetic counseling in adult polycystic kidney disease
Authors: Sahney Shobha , Weiss Lester , Levin Nathan W. , Opitz John M.
Published: June 2005

We evaluated 22 patients with end‐stage renal disease (ESRD) due to adult polycystic kidney disease (APKD) to assess their knowledge of the hereditary nature of the condition and to determine whether they received adequate genetic counseling. Patients were evaluated by means of a questionnaire and a review of their medical records. Only 5 of 22 (23%) knew their disorder was hereditary at the time of diagnosis, and in only 4 (18%) was genetic counseling suggested. In no instance had proband and spouse received genetic counseling together. Diagnostic studies of children at risk were rarely suggested.

We also evaluated the children of 9 probands for APKD. Of 26 children evaluated, 17 had APKD (65%). Sixteen had no children at the time of testing. All but two of the 26 were less than 25 years old. Of the probands' children over 15 years of age, 55% knew the name of the condition in the family but only 9% knew they should be tested. Our study demonstrated inadequacy of genetic counseling and follow‐up in this group of patients; we suggest that referral for counseling become a routine part of their management. Early diagnosis and effective counseling has the potential benefit for the individuals of making rational reproductive decisions appropriate for their situation. Counseling may have to be repeated during the course of the patients' disease, as their perception of risk may change with time. With advances in dialysis and transplantation, ESRD may not be as devastating in years to come as it is now.
Cytogenetic findings in 200 children with mental retardation and multiple congenital anomalies of unknown cause
Authors: Coco Roberto , Penchaszadeh Victor B. , Opitz John M.
Published: June 2005

We report a cytogenetic study of 200 children with mental retardation and three or more major or minor congenital anomalies. In all cases, the chromosomes were studied with conventional staining methods (nonbanding) and with at least one of the following techniques: Q, G, or R banding. In a few patients, C banding and in vitro differentiation with BUDR and acridine orange (R banding) were also used. In patients with structural abnormality, parental chromosomes were studied using the same techniques.

A chromosome abnormality was found in 42 patients (21%). Of these, 16 (8%) had complete or mosaic aneuploidies (11 autosomal and 5 gonosomal); and 26 (13%) had structural defects. In 21 of the latter the structural abnormality occurred as a de novo rearrangement, and in 5 the defect was inherited from a parent carrier of a balanced rearrangement. The contribution of chromosome aberrations to the cause of (idiopathic) MCA/MR syndromes is discussed.
The acrocallosal syndrome
Authors: Nelson M. M. , Thomson A. J. , Opitz John M.
Published: June 2005

We report two unrelated patients, a three‐year‐old girl and an 8 8/12‐year‐old boy with the newly described “acrocallosal” syndrome. The main manifestations of the syndrome are unusual facial appearance, pre‐ and postaxial polydactyly, mental retardation, and absence of the corpus callosum. Cause remains unknown.
Marker X syndrome in an oriental family with probable transmission by a normal male
Authors: Rhoads Frances A. , Oglesby Allan C. , Mayer Martha , Jacobs Patricia A.
Published: June 2005

We report an oriental family with sex‐linked mental retardation, macroorchidism, and a marker or fragile site on the X chromosome–mar(X)(q28). The three affected males resemble clinically most previously reported affected Caucasians. The marker was present in four females 40–70 years old, including one with normal intelligence. Transmission of the disorder appears to have taken place through a clinically normal male to his grandson.
Psychological aspects of genetic counseling. II: Quantitative analysis of a transcript of a genetic counseling session
Authors: Kessler Seymour , Jacopini A. Gioia , Opitz John M.
Published: June 2005

The Bales system of scoring small group interactions was used to analyze a transcript of a preamniocentesis (genetic) counseling session in which a husband (H), wife (W), and a male counselor (C) participated. Scoring required the subdivision of communication into the smallest meaningful and scorable units, assigning each unit one of twelve possible category scores and designating the initiator and intended recipient(s) of the unit. The categories included “positive” and “negative” reactions, questions and attempted answers. Over half the units were found to consist of interactions in which information, orientation, and clarification were provided. C initiated 54% of all units of which three‐quarters consisted of factual information regarding amniocentesis, genetic risks, Down syndrome, and mental retardation. C interacted significantly more frequently with W than with H, but units directed toward H were significantly more positive than those toward W. One interaction, in which C responded to affective material, significantly altered the subsequent frequency and direction of units; H became more verbal and there was an increase in further affective expression. Although evidence of persuasion was present, no directiveness was demonstrated. The data show that quantitative study of genetic counseling is feasible. Further research on different counseling styles and on the influence of specific interventions on later outcome has been undertaken.
Spinal dysraphia as an autosomal dominant defect in four families
Authors: Fineman Robert M. , Jorde Lynn B. , Martin Rick A. , Hasstedt Sandra J. , Wing S. Douglas , Walker Marion L.
Published: June 2005

Four families were selected randomly on the basis of the occurrence of spina bifida cystica and/or spina bifida occulta in one or more family members. Sixty‐three relatives were studied clinically and roentgenologically; their roentgenograms were evaluated blindly. Twenty‐eight were clinically and roentgenologically normal; 35 were diagnosed as having spina bifida occulta (SBO), spina bifida cystica (SBC), vertebral anomalies, and/or external defects usually interpreted as evidence for SBO. Excluding one proband we found the frequency of SBO to be 19/51 (37%) and the frequency of all types of spinal/vertebral defects (excluding five probands) to be 30/58 (52%). The distribution of these defects in the four families was analyzed using likelihood methods corrected for random ascertainment.

The log likelihood values for sporadic, recessive, and dominant models were −26.69, −20.95, and −18.90, respectively, indicating a higher likelihood of autosomal dominant inheritance than sporadic occurrence or recessive inheritance. The penetrance probability in this dominant model, estimated by maximum likelihood, is 0.749 ± 0.100. Further examination of these data suggests that SBO and SBC represent different expressions of the same dominant gene in these kindreds.
Atelosteogenesis
Authors: Maroteaux P. , Spranger J. , Stanescu V. , Le Marec B. , Pfeiffer R. A. , Beighton P. , Mattei J. F. , Opitz John M.
Published: June 2005

The name atelosteogenesis is proposed for a lethal chondrodysplasia characterized by deficient ossification of various bones, notably the humerus, femur, thoracic spine, and hand bones. Clinically, the patients have micromelic dwarfism with incurvated legs, club feet, often dislocation of the elbows, and, rarely, a cleft palate. The most characteristic radiographic signs are incomplete ossification of the vertebral bodies with coronal clefts of the lumbar and hypoplasia of the upper thoracic vertebral bodies, a distal hypoplasia and club shape of the humerus and the femur, and the lack of ossification of single phalanges and metacarpals in most patients. Histologically, there are clusters of chondrocytes surrounded by fibrous capsules and, more frequently, degeneration zones containing degenerated chondrocytes and copious amounts of metachromatic material in the epiphyses and the basal zone of the growth plate.
Spondylometepiphyseal dysplasia, strudwick type
Authors: Anderson C. E. , Sillence D. O. , Lachman R. S. , Toomey K. , Bull M. , Dorst J. , Rimoin D. L. , Opitz John M.
Published: June 2005

The clinical and radiographic observations in eight patients, radiographs on an additional six patients, and morphologic observations on chondro‐osseous tissue from two of these 14 patients form the basis for delineating an entity distinct from the heterogeneous group of skeletal dysplasia involving spine and tubular bones, the spondyloepiphyseal, and spondylometaphyseal dysplasias. Disproportionately short limbs and delayed epiphyseal maturation are present at birth, and the entity is radiographically indistinguishable from spondyloepiphyseal dysplasia (SED) congenita during infancy. The metaphyseal change that allows identification of the entity described here develops during early childhood, and radiographically is seen as “dappling,” ie, the mottled appearance of alternating zones of osteosclerosis and osteopenia. Severe scoliosis and cord compression may be important clinical problems related to the spine changes in adulthood. We have identified one family with two affected sibs and normal parents, suggesting autosomal recessive inheritance and distinguishing the entity from SED congenita that has autosomal dominant inheritance.
Deafness, onycho‐osteodystrophy, mental retardation (DOOR) syndrome
Authors: Nevin N. C. , Thomas P. S. , Calvert J. , Reid M. McC.
Published: June 2005

We report two patients with sensorineural deafness, onycho‐ and osteodystrophy of fingers and toes, and mental retardation (DOOR syndrome). In addition, one patient, the only son of consanguineous parents, had seizures and hypoplasia of the optic nerves. The second patient, a male, was the only one affected in a sibship of three.
Prenatal diagnosis of cyclopia
Authors: Elejalde B. Rafael , de Elejalde Maria Mercedes , Hamilton Phillip R. , Christenson Richard , Broekhuizen Fredrik , Opitz John M.
Published: June 2005

Two fetuses affected by cyclopia, holoprosencephaly, and malformations of the nasopharynx were diagnosed prenatally in association with acute polyhydramnios. The facial malformations, confirmed by fetography‐amniography and proven at birth, were suspected on the basis of the ultrasonographic examination.
Age‐of‐onset heterogeneity in Huntington disease families
Authors: Pericak‐Vance M. A. , Elston R. C. , Conneally P. M. , Dawson D. V. , Opitz John M.
Published: June 2005

Ten Huntington disease (HD) families are analyzed using maximum likelihood methods to study age‐of‐onset (AO) heterogeneity. Both age of onset and age at examination are used in calculating an individual's likelihood of being affected; familial correlations and family structure are not included in the model. The model allows for differences in current age distributions by considering the distribution of age of onset conditional on age at examination.

Families are grouped according to family type (ie, juvenile‐onset families and adult‐onset families) and then analyzed within each family type as well as between the two types, using both a chi‐square test for heterogeneity and F‐ratios. The results of the chi‐square analyses indicate heterogeneity in AO among the individual families as well as between the two family types. However, the results of the F‐ratios show no significant difference between the two family types, indicating that the difference in the chi‐square analysis between the two family types is mostly owing to variation among the families. Thus, the results demonstrate that the existing variation in age of onset between these two family types is dwarfed by the magnitude of the variation among the families within each type. This implies that families of sufficient size should be evaluated individually for age‐of‐onset data for the purpose of either genetic counseling or linkage studies.
Antley‐Bixler syndrome in sisters: A term newborn and a prenatally diagnosed fetus
Authors: Schinzel Albert , Savoldelli Guido , Briner Jakob , Sigg Peter , Massini Carlo , Opitz John M.
Published: June 2005

Sisters with the Antley‐Bixler syndrome are reported herein. The first infant died at 14 days of respiratory failure and the following findings characteristic of the syndrome: craniosynostosis of coronal and lambdoid sutures, brachycephaly, frontal bossing, severe midface hypoplasia with proptosis and choanal stenosis/atresia, humero‐radial synostosis, medial bowing of ulnae, long slender fingers with camptodactyly, narrow iliac wings, anterior bowing of femora, cardiac and renal malformations. Unlike two previously published cases, she did not have connatal fractures, but she had vaginal atresia. Ultrasound examination in a subsequent pregnancy showed immobility at the elbows of the fetus, humero‐radial synostosis, medial bowing of ulnae, and long hands and fingers. The fetus also had mild bowing of femora. The pregnancy was terminated in the 21st week and the findings were confirmed by clinical and radiologic examinations. Additional autopsy findings included cardiac and renal malformations. The Antley‐Bixler syndrome is a recognizable malformation syndrome with a probable autosomal recessive mode of inheritance, which can be diagnosed in the fetus by midtrimester ultrasound examination.
Syndrome of acrofacial dysostosis, cleft lip/palate, and triphalangeal thumb in a brazilian family
Authors: Richieri‐Costa A. , Gollop Thomaz R. , Colletto G. M. D. D. , Opitz John M.
Published: June 2005

We describe two daughters of a nonconsanguineous couple. Both had facial and skeletal anomalies, but in quantitatively and qualitatively different ways. In one patient signs of mandibulofacial dysostosis are associated with anomalies of the radial rays of both arms. In the other, cleft lip and cleft palate are associated with hypoplastic thumbs. Clinical and genetical aspects of present case are discussed.
Blood groups, immunoglobulin allotypes and dermatoglyphic features of patients with amyotrophic lateral sclerosis and parkinsonism‐dementia of guam
Authors: Garruto R. M. , Plato C. C. , Myrianthopoulos N. C. , Schanfield M. S. , Gajdusek D. C. , Herrmann Jürgen
Published: June 2005

Blood group frequencies, immunoglobulin allotypes, and dermatoglyphic patterns were determined on patients with amyotrophic lateral sclerosis (ALS) and parkinsonism‐dementia (PD), two chronic, degenerative, neurologic disorders of unknown cause found commonly among the Chamorros of the Mariana Islands, in an attempt to identify a specific genetic or phenetic marker associated with either disorder. With the exception of the Kidd system, no significant differences were found in blood group frequencies nor in immunoglobulin allotypes between ALS patients, PD patients, and unaffected controls. The dermatoglyphic analysis demonstrated that ALS patients had higher frequencies of palmar patterns and accessory triradii in the IV interdigital area, and PD patients had significantly higher frequencies of complete simian creases and of palmar patterns in the thenar/I interdigital area than unaffected controls. The frequencies of the remaining dermatoglyphic traits showed no significant differences. We conclude that none of the marker systems tested show a particular pattern of association in patients and controls or a genetic predisposition to either disorder, and that early identification of at‐risk individuals remains elusive.
Complex segregation analysis and computer‐assisted genetic risk assessment for Duchenne muscular dystrophy
Authors: Williams Wick R. , Thompson Margaret W. , Morton Newton E. , Opitz John M.
Published: June 2005

Two hundred forty‐four Toronto pedigrees of Duchenne muscular dystrophy patients have been partitioned into nuclear families with pointers for complex segregation analysis under a mixed model. The model takes into account the major X‐linked locus and a multifactorial transmissible component for creatine kinase activity in females. The incidence in the province of Ontario is estimated to be 292 per million male births. The proportion of sporadic cases is 1/3, demonstrating equal mutation rates in males and females. A multifactorial component (H = 0.379) contributes to family resemblance for creatine kinase measurements. Examples are presented of the application of a computer program, COUNSEL, to derive genetic risks for genetic counseling with consideration of the multifactorial component.
New, autosomal dominant form of ectodermal dysplasia
Authors: Tuffli Gordon A. , Laxova Renata , Opitz John M.
Published: June 2005

We describe a 15‐year‐old boy with an ectodermal dysplasia syndrome (EDS) associated with unilateral adrenal cyst. The EDS combination of aplasia cutis verticis, hypohidrosis, nipple/breast hypoplasia, onychodysplasia, and delayed dental eruption with minor tooth anomalies has not been previously reported as an autosomal dominant trait. The association with adrenal cyst may alert other units to review their experience to determine if such combination is more than a coincidence.
Aqueductal stenosis leading to hydrocephalus—an unusual manifestation of neurofibromatosis
Authors: Horwich Arthur , Riccardi Vincent M. , Francke Uta , Opitz John M.
Published: June 2005

Two brothers and an unrelated male with neurofibromatosis (NF) developed hydrocephalus in childhood. Aqueductal stenosis (AS) was demonstrated by ventriculography and required shunt operation. Genetic counselors had to decide whether to invoke an X‐linked gene for AS or whether AS could be caused by the NF mutation. Reports of 13 patients of both sexes with AS and NF suggest that AS with resulting hydrocephalus may be a rare manifestation of the NF gene. AS should be looked for in young NF patients with signs of hydrocephalus or with neurologic abnormalities.
Hb F levels, longevity of homozygotes and clinical course of sickle cell anemia in Brazil
Authors: Hutz Mara H. , Salzano F. M. , Adams J. , Opitz John M.
Published: June 2005

A sample of 354 individuals with sickle cell anemia ascertained in the city of Rio de Janeiro was studied to investigate the relationships between Hb F level, morbidity, and mortality. The mean Hb F level was 6.41 ± 5.21%. The relationship between age and the proportion of Hb F can be described as a quadratic polynomial distribution, the level falling from approximately 11% in the first year to 4% at 25 years and then rising proportionally after 30 years. The correlations between Hb F level and 140 variables, including hematological values, signs and symptoms of the disease, as well as therapeutic requirements, showed that the patients with high Hb F levels are less anemic and have a more benign course. Several significant correlations (between amount of Hb F and the following clinical signs: pallor of mucous membranes, jaundice, cholelithiasis, leg ulcers, bronchial asthma, increased pulmonary vascularity, left ventricular hypertrophy, and osteomyelitis) are being reported here for the first time.
The dup(3)(p25 → pter) syndrome: A case with holoprosencephaly
Authors: Martin Nicole J. , Steinberg Barry G. , Opitz John M.
Published: June 2005

We report a patient with dup(3p) syndrome with holoprosencephaly. This infant is compared with 17 others reported previously with banding studies. In 72% of cases the duplication derived from a mother with a balanced translocation; 78% of affected individuals are males. The most common anomalies are characteristic facial changes, congenital heart defects, and hypoplasia of male genitalia. Holoprosencephaly has not been reported before in the dup(3p) syndrome.
The Kenny‐Caffey syndrome: Growth retardation and hypocalcemia in a young boy
Authors: Lee W. K. , Vargas A. , Barnes J. , Root A. W.
Published: June 2005

A 2‐year‐old black boy with the Kenny‐Caffey syndrome was first evaluated because of growth retardation and hypocalcemia. Hypothalamic‐pituitary function was normal. Basal serum somatomedin C levels were normal for age, but did not increase during short‐term administration of human growth hormone. Serum immunoreactive parathyroid hormone levels remained inappropriately low during spontaneous and induced hypocalcemia, indicating that hypocalcemia was the consequence of hypoparathyroidism. The manifestations of 15 patients with this syndrome are tabulated.
The campomelic syndrome: Review, report of 17 cases, and follow‐up on the currently 17‐year‐old boy first reported by Maroteaux et al in 1971
Authors: Houston C. Stuart , Opitz John M. , Spranger Jürgen W. , Macpherson Roderick I. , Reed Martin H. , Gilbert Enid F. , Herrmann Jürgen , Schinzel Albert
Published: June 2005

We report 17 cases of the campomelic syndrome (CS) and a follow‐up of one of the original patients of Maroteaux et al who is now 17 years old. Our review is based on 97 patients, including our own.

An infant with the CS presents at birth with spectacularly short and bowed femora and tibiae. The initial chest radiograph confirms the diagnosis by demonstrating extremely small bladeless scapulae and hypoplastic pedicles of many thoracic vertebrae. Ossification of the sternal segments, pubis, talus, and knee epiphyses is also retarded. Usually the hips are dislocated and talipes equinovarus deformities are present. There is a small chondrocranium and a disproportionately large neurocranium.

The bell‐shaped chest, narrow superiorly, does not explain the degree of respiratory distress that soon ensues. Narrow airways from defective tracheo‐bronchial cartilage can often be demonstrated on the radiograph, but micrognathia, retroglossia, cleft palate, hypoplastic lungs, and even CNS‐based hypotonia contribute to the respiratory problem.

Internal anomalies include frequent absence of olfactory bulbs and tracts and dilatation of cerebral ventricles, heart defects (PDA, VSD, stenosis of aortic isthmus), hydroureter and hydronephrosis, renal hypoplasia, and rarely renal cysts.

We conclude on the basis of mostly sporadic (“chance isolated”) occurrence, several instances o parental consanguinity, and familial occurrence that the CS is probably owing to the homozygous state of an autosomal recessive gene. Affected males may have normal genitalia with desceding testes or female genitalia with streak‐like gonadal rudiments, or any stage of male pseudohermaphroditism between these two extremes. Whether the H‐Y antigen deficiency observed in “sex reversed” CS males is a primary or secondary defect remains unsettled.

This not uncommon syndrome is usually fatal within days, weeks, or months. However, several young survivors are known with initially normal neurologic status and psychomotor development. Our patient 17 is 17 years old, has an estimaged IQ of 45, and a hearing loss, which may reflect numerous middle‐ear infections and malformations of the middle ear.
Previously undescribed syndrome of craniofacial, hand anomalies, and sensorineural deafness
Authors: Sommer Annemarie , Young‐Wee Theresa , Frye Thomas
Published: June 2005

We describe in a mother and her infant daughter a previously unreported syndrome of unusual craniofacial, hand, and digital anomalies. Both mother and child have a flat facial profile, hypertelorism, hypoplastic nose with slit‐like nares, and a sensorineural hearing loss. Common radiographic manifestations include small maxilla, absent or small nasal bones, and ulnar deviation of the hands. This is either an autosomal dominant or X‐linked trait.
Discordance for the Kleeblattschädel anomaly in monozygotic twins with thanatophoric dysplasia
Authors: Horton William A. , Harris David J. , Collins Debra L. , Opitz John M.
Published: June 2005

We describe monozygotic twins with thanatophoric dysplasia who were discordant for the Kleeblattschädel anomaly, but were identical in all other respects, including the histologic appearance of the endochondral growth plate. The observation suggests that the skull anomaly represents a variable manifestation of thanatophoric dysplasia, and that its occurrence in an infant with this bone dysplasia should not alter the low recurrence risk generally given.
Autosomal dominant recurrent encephalopathy of childhood
Authors: Neuhäuser Gerhard , Eichner Jerrold M. , Opitz John M. , DeMyer W. , Guggenheim M.A.
Published: June 2005

Recurrent encephalopathy affecting cerebellar and extrapyramidal structures was observed in five members of two families. The syndrome is characterized by sudden onset of truncal ataxia, occasionally accompanied by lethargy and impairment of speech. Choreic and athetoid movements were present, and there was loss of deep tendon reflexes with presence of pathological reflexes. Onset of the disease was early in childhood. Attacks lasted for days to weeks; residual symptoms comprising speech impairment and incoordination were seen in some patients. Both sexes were affected. The pedigrees suggest autosomal dominant inheritance. Pathogenesis remains unexplained by the laboratory studies done; metabolic or immunological processes predisposed by genetic factors are suggested. Similar reports from the literature are discussed; no identical family could be found.
Cytogenetic differentiation of Fanconi anemia, “idiopathic” aplastic anemia, and Fanconi anemia heterozygotes
Authors: Cervenka Jaroslav , Hirsch Betsy A. , Opitz John M.
Published: June 2005

We have analyzed chromosome breaks in 8 patients with Fanconi anemia (FA), 42 with “idiopathic” aplastic anema (AA), 15 first‐degree relatives of FA patients, and 13 controls. Their lymphocytes were treated in culture with three concentrations of mitomycin‐C (MMC). A 60‐fold increase in breaks was observed in FA patients as compared to AA patients, regardless of severity of clinical signs. The MMC‐stress test was standardized to clearly differentiate FA from other pancytopenias in doubtful cases. Also, the effect of storage of MMC in solution was investigated. The data on SCEs of 12 subjects tested, 10 mo apart, showed an inverse relationship between length of storage of MMC and chromosome damage. The 10‐month‐old solution induced only one half as many SCEs as it induced at 4 months.

Further, the usefulness and power of diepoxybutane (DEB) in detection of FA heterozygotes was investigated in 12 first‐degree relatives of patients with Fanconi anemia and 12 healthy controls. The mean number of chromosome breaks per mitosis by DEB stress in obligate heterozygotes was 0.08 in comparison to 0.06 in controls. Four of twelve control subjects showed proportions of breaks almost identical to or higher than those of FA heterozygotes, ie, 0.12, 0.10, 0.10, and 0.11 breaks per mitosis. The responses of healthy controls to DEB could be separated into two groups: one with mean chromosome breaks of 0.11 per mitosis, and a second with mean breaks of 0.04 per mitosis. Thus, it appears that heterozygote detection by DEB stress of cultured lymphocytes is not unequivocal.
Unusual combination of genetic defects in a Sicilian boy: Gγ Aγ δβ thalassemia, Gγ Aγ heterocellular HPFH, βº thalassemia, and albinism
Authors: Schilirò G. , Pavone L. , Romeo M. A. , Russo A. , Musumeci S. , Russo G. , Opitz John M.
Published: June 2005

We describe the clinical and hematological findings in a 5‐year‐old boy with Gγ Aγ δβ thalassemia, a Gγ Aγ heterocellular form of HPFH, βº thalassemia, and albinism. Clinically he manifested only the characteristics of β‐thalassemia trait and not the typical picture of doubly heterozygous β thal/δβ thal. The simultaneous presence of heterocellular HPFH improves γ chain synthesis, thus reducing the α chain excess. It is also possible that gene expression can be modified by the presence of other genetic anomalies.
The dynamics of quantifiable homeostasis I. The individual
Authors: Murphy Edmond A. , Trojak Joseph E. , Opitz John M.
Published: June 2005

In this field of enquiry, “homeostasis” is understood in the sense of Bernard, Cannon, and Wiener, that is, with the system of continuous adjustments, in a trait not inherently stable, to meet the challenges of the environment. It is shown that the clinical fitness of a trait may depend on factors other than the mean or the variance. In particular the broad pattern of variation of the phenotype may be of importance and hence the characteristics of the homeostatic mechanisms for the control of traits subject to variation: notably the homing value (the “setting” of the homeostat), and the strength with which the organism responds to departures from this value. These parameters are related, but perhaps only remotely, to the traditional notion of the value of a phenotype. In general, where the environmental value is variable, there exist circumstances in which the optimal control would be neither extremely tight nor extremely loose. For instance, anticipatory action on the part of the body may be vitiated by too tight a control. Some illustrations are given of genetic disorders in which there is a fault in the strength of control. While neither the pattern of inheritance nor the impact on the species is explored in detail, the broad implications are indicated. Compromise adjustments are explored where two or more traits are regulated through the same homeostatic device.
Maternal cell contamination of amniotic fluid cell cultures: Results of a U.S. nationwide survey
Authors: Benn Peter A. , Hsu Lillian Y. F. , Karp Laurence E.
Published: June 2005

A nationwide survey has been carried out to establish the incidence and factors determining maternal cell contamination (MCC) of amniotic fluid cultures. One hundred sixty‐two cytogeneticists and medical geneticists were invited to participate, and data were collected from 71 laboratories, representing 91,131 amniocenteses. The incidence of recognized cases of MCC was 0.148%, of which 0.123% were recognized as an admixture of male and female cells, the latter often being present in multiple cultures. A further 0.025% of cases were ascertained as a result of unexpected pregnancy outcome. In many of these cases where misdiagnosis occurred, a less than optimal number of cells or cultures were analyzed. Since MCC would generally not be recognized when the fetal sex is female, the true incidence of MCC would be approximately twice these values.

MCC incidence was 2½ times lower when the first few milliliters of amniotic fluid were not used for cell culture and appeared to be more common when wider gauge needles were used for the amniocentesis. Twenty‐six percent of MCC cases represented referrals for reasons other than advanced maternal age. Approximately 35% of all cases with MCC were those in which the amniotic fluid was bloody. Cultures with MCC appeared to show no unusual growth properties.

It is concluded that the most likely source of MCC is from the outgrowth of maternal tissue removed by the needle. Specific recommendations for dealing with MCC are that 1) the first one or two milliliters of amniotic fluid are not used for cell culture, 2) at least 20 cells from two independent cultures are counted wherever possible, 3) parental polymorphisms are studied in cases where a 46,XX and 46,XY admixture is found, and 4) cases referred fo biochemical studies on cultured cells also receive cytogenetic analysis to help rule out the possibility of MCC.
Familial idiopathic gonadotropin deficiency: A hypothalamic form of hypogonadism
Authors: Toledo S. P. A. , Luthold W. , Mattar E. , Opitz John M.
Published: June 2005

To date, familial idiopathic gonadotropin deficiency (FIGD) has not been delineated as either a hypothalamic or a pituitary form of hypogonadism. Leydig cell sensitivity to human chorionic gonadotropin (HCG) has also been suggested as subnormal in FIGD. Also, in a few previously reported families the Kallmann syndrome was not clearly ruled out.

Data herewith reported on three sibs with FIGD supported the following conclusions: (1) FIGD is due to insufficient hypothalamic luteinizing hormone‐releasing hormone (LRH) secretion, (2) the sensitivity of Leydig cells to HCG is normal, (3) LRH treatment may be helpful in these patients, (4) an associated hypothalamic‐pituitary‐prolactin (PRL) dysfunction may also be present, and (5) FIGD and the Kallmann syndrome are different entities having a similar pathophysiology but different cause and overall clinical picture.
Plasma creatine kinase and myoglobin levels, before and after abortion, in human fetuses at risk for Duchenne muscular dystrophy
Authors: Edwards R. J. , Rodeck C. H. , Watts D. C. , Opitz John M.
Published: June 2005

Plasma levels of creatine kinase (CK) were measured in 14 abortuses, nine of which were at risk for Duchenne muscular dystrophy (DMD). The plasma CK level was found to be increased in all abortuses, compared with the value obtained by fetoscopy before the termination. The causes of the increase in CK level were found to be 1) method of termination, 2) physical state of the abortus at delivery, 3) delay between delivery of the abortus and taking the blood sample, and 4) site of blood sampling. It is concluded that even under optimum conditions of termination the plasma creatine kinase level of the abortus is significantly raised above the true level; hence, this measurement is not reliable as a guide to the genetic status of the fetus.

Cardiac leakage was the main source of the raised plasma CK level in the abortus and this was corroborated by measurement of myoglobin levels.
Effects of genetic counseling on Duchenne muscular dystrophy families in Brazil
Authors: Zatz Mayana , Opitz John M.
Published: June 2005

We report the preliminary results of a follow‐up study of 574 females at‐risk for Duchenne dystrophy, recontacted 3 to 13 yr after genetic counseling (GC). Among them, 290 are younger than 18 yr or still unmarried.

The effectiveness of GC (reproductive performance) in the remaining group is analyzed in terms of procreation, rate of sterilization, and mean number of children. The observed data suggest that females at‐risk involved in GC had about 169 children less than their normal, nonaffected brothers. In terms of prevention this would correspond roughly to 42 Duchenne affected boys and 42 carrier girls.
The dynamics of quantifiable homeostasis. II. Characterization of linear processes
Authors: Renie W. Andrew , Murphy Edmond A.
Published: June 2005

This paper deals with the representation of physiological homeostatic processes by mathematical models that lead to lag‐differential equations. It deals exclusively with feedback processes that are linear. It is surmised that in the response to standard perturbations from equilibrium, in many systems the strength at which the restorative force works (denoted by the constant b) is a genetic characteristic, while the average or homing value may or may not be. The class of equations with linear feedback is solved. The solution provides predictions against which experimental data may be tested. Three types of displacement from the homing value are recognized: drifts, catastrophes, and saccades. Several methods of evaluating the mathematical functions are described. They are forward recursion, backward recursion, numerical integration, steady‐state solutions, and inversion of the Heaviside expansion of the Laplace transform. Conditions for homeostatic processes that result in damped nonoscillating responses, damped oscillating responses, stable oscillations, and uncontrolled oscillations are derived. The concept of an associated penalty that depends on the degree of displacement from the homing value is discussed. Penalties are evaluated by numerical integration for linear, quadratic, and cubic costs. Costs for polynomial functions may be found by linear weighting. The optimum strength of response (ie, the one that produces the minimum cost) is calculated for each of these cost functions.
Familial t(4;13) with abnormal offspring in three generations
Authors: Najafzadeh Touran M. , Littman Vicki A. , Dumars Kenneth W. , Opitz John M.
Published: June 2005

A newborn infant girl died at I day and was found to have severe intrauterine growth retardation, microcephaly, cleft lip and palate, single umbilical artery, absent thumbs, bicuspid pulmonic valve, pulmonary hypoplasia, malrotation of large and small bowel, and a 46,XX,13q+ chromosome constitution derived from a paternal t(4;13)(q25;q32) with resulting del(13q) and dup(4q). The paternal grandmother and greatgrandmother also carried the balanced translocation. Each had had a child with multiple congenital anomalies including “duplex” thumbs. However, a chromosome analysis was not performed on these abnormal infants. Our patient's clinical and cytogenetic manifestations are discussed in relation to the Niebuhr map of chromosome 13.
Familial clustering of situs inversus totalis, and asplenia and polysplenia syndromes
Authors: Niikawa Norio , Kohsaka Shinobu , Mizumoto Masahiko , Hamada Isamu , Kajii Tadashi , Opitz John M.
Published: June 2005

We report on a family in which a male infant had the asplenia syndrome, a younger brother had the polysplenia syndrome, and their father had situs inversus totalis. The occurrence of the asplenia and the polysplenia syndromes in a sibship of the present family and in two other previously reported sibships indicates that the two syndromes are causally and pathogenetically related to each other. If it is assumed that the father had an incomplete form of the polyasplenia complex, then the condition in this family either is an autosomal dominant trait or is multifactorially determined.
Autosomal or X‐linked recessive syndrome of congenital lymphedema, hypoparathyroidism, nephropathy, prolapsing mitral valve, and brachytelephalangy
Authors: Dahlberg Philip J. , Borer William Z. , Newcomer Kermit L. , Yutuc Wilfrido R.
Published: June 2005

Two brothers were found to have an unusual congenital syndrome of lymphedema, pulmonary lymphagiectasia, hypoparathyroidism, hereditary nephropathy, prolapsing mitral valve, and other somatic abnormalities.
Hematological abnormalities in newborn infants with down syndrome
Authors: Miller Marvin , Cosgriff Janice M. , Opitz John M.
Published: June 2005

The hematological status of 81 infants with Down syndrome was reviewed retrospectively. Twenty babies had no hematological evaluation, 33 had a normal hematological status, and 28 had at least one abnormality, either of hematocrit, white cell count, or platelet count. Among these were 18 babies with increased hematocrit, one with decreased hematocrit, four with decreased platelet count, one with increased white cell count, three with increased hematocrit and decreased platelet count, and one with increased platelet count and increased white cell count. Some of these babies were evaluated for neoplasia or sepsis; however, in all the abnormal blood findings disappeared by 3 weeks without evidence of malignancy or infection. We conclude that hematological abnormaltites with a benign natural history are common in Down syndrome infants.
Tricho‐dento‐osseous syndrome: Heterogeneity or clinical variability
Authors: Shapiro Steven D. , Quattromani Frank L. , Jorgenson Ronald J. , Young Robert S. , Opitz John M.
Published: June 2005

Tricho‐dento‐osseous (TDO) syndrome is an autosomal dominant disorder characterized by abnormalities of hair, teeth, and bone. We report on a family that seems to illustrate further clinical heterogeneity in the TDO syndrome. Although variable expression of a single TDO gene cannot be ruled out, the manifestations observed in this and other reported families appear to fall into distinct subtypes. This suggests the possibility that the clinical subtypes represent distinct genetic entities.
Duplication of the distal segment of 14q
Authors: Atkin Joan F. , Patil Shivanand , Opitz John M.
Published: June 2005

We describe a child with duplication of the distal segment of 14q. Her father carries a balanced translocation between chromosomes 14 and 15. A detailed table compares her clinical findings with those of the seven previously published cases and an additional three new cases in an effort to define a recognizable syndrome. Serum α‐1 antitrypsin levels and PI typing did not help to localize the α‐1 antitrypsin gene locus.
Discovery of a connective tissue dysplasia in the Martin‐Bell syndrome
Authors: Opitz John M. , Westphal Joan M. , Daniel Art , Optiz John M.
Published: June 2005

The fact that a connective tissue dysplasia is a component of the Martin‐Bell syndrome was a fortuitous discovery. A 26‐month‐old developmentally delayed boy had many signs of a connective tissue dysplasia for which he was referred to a University center where he was found to be fragile (X)‐positive without confirmation of a connective tissue problem. Sensitized by these events and observations, we were able to predict at a glance in an unrelated family the fragile (X)‐positive status of 2 subsequently referred brothers with mental retardation and prominent manifestations of connective tissue dysplasia. Thus, the Martin‐Bell syndrome is an incompletely recessive, pleiotropic trait involving CNS, testes and connective tissues. The characteristic facial appearance of affected males largely represents interaction of mental retardation, congenital CNS based muscle hypotonia and connective tissue dysplasia. At the 1983 NIH workshop on XLMR there was a general consensus that a connective tissue dysplasia is a component of the Martin‐Bell syndrome, a fact since confirmed by others on the basis of objective measurements of finger joint hypermobility and frequent presence of mitral valve prolapse.
Consideration of connective tissue dysfunction in the fragile X syndrome
Authors: Hagerman Randi J. , Van Housen Karen , Smith Ann C. M. , McGavran Loris , Opitz John M.
Published: June 2005

Eleven cytogenetically documented patients with the fragile X syndrome were evaluated for hyperextensibility of the finger joints and the presence of other manifestations of connective tissue dysfunction. All of the patients had hyperextensibility of several finger joints and many had features such as flat feet, highly arched palate and the ability to voluntarily dislocate finger joints. These traits, particularly hyperextensibility of the joints, are a useful aid in the clinical diagnosis of the fragile X syndrome.
A form of X‐linked mental retardation with marfanoid habitus
Authors: Lujan J. Enrique , Carlin Mary Esther , Lubs Herbert A. , Opitz John M.
Published: June 2005

A kindred has been studied in which mental retardation and marfanoid clinical features are present in several individuals. The pedigree is consistent with X‐linked recessive inheritance. Four affected males aged 12‐18 years and four obligate carriers have been identified. Clinical findings in the 4 affected males included a tall slender habitus (3) (the fourth was tall but muscular), a long‐narrow face (3), large head (4), highly arched palate (4), small mandible (4), abnormal speech (4), hypernasal voice (3), joint hyperextensibility (3), borderline to large testes (3), pectus excavatum (2), atrial septal defect (1), and a double row of teeth (1). Mental retardation (4) ranged from mild to severe; abnormal behavior included hyperactive and aggressive behavior (2), autistic‐like (1) and jovial behavior (1). One and possibly two, males had absence of the corpus callosum. Chromosome studies on all were normal; no marker X was observed. We believe this family probably represents a new form of X‐linked mental retardation.
Ring chromosome 14 and immunoglobulin locus
Authors: Krawczun M. , Melink G. , Cervenka J. , Opitz John M.
Published: June 2005

A 2.5‐yr‐old girl was evaluated for seizurelike episodes and psychomotor and growth retardation. Cytogenetic study showed a ring 14 chromosome in most cells, with some cells having monosomy 14. Rarely, a cell showed a double ring chromosome 14. Both parents had normal chromosomes. Because serum immunoglobulins have been mapped to the distal portion of 14q, we attempted to correlate Ig levels with the deletion involved in the formation of this ring. No decrease in IgG, IgM, IgA, IgE, and IgD serum levels was observed.

The normal serum Ig levels found in the proposita are compatible with the suggestion that the Ig loci are not located on the terminal portion of 14q but more proximally in band 14q32. However, because Gm and Am allotyping was not available mapping was not conclusive.