bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytogenetic findings in Roberts‐SC phocomelia syndrome(s)
Authors: Tomkins Darrell , Hunter Alasdair , Roberts Maureen
Published: June 2005

Roberts syndrome and SC phocomelia syndrome are an autosomal recessive condition of prenatal and postnatal growth retardation, symmetrical limb reduction, and craniofacial abnormalities. A distinction has been made between the two syndromes on the basis of relative severity of these manifestations. Where chromosome studies have been carried out, most have been reported as normal. However, there have been two reports of consistent centromere abnormalities; one in a patient with SC phocomelia (pseudothalidomide syndrome), the other in a patient with Roberts syndrome. Four patients with similar phenotypic manifestations have recently been shown in our laboratory to have the same centromere puffing and splitting. These four patients had other clinical manifestations in common, including bilateral corneal opacities, microcephaly, absence of radii, limited extension at knees and elbows, apparent enlargement of the phallus, and survival beyond the neonatal period.
A family study of congenital inguinal hernia
Authors: Czeizel A. , Gárdonyi Judit
Published: June 2005

In fathers and mothers of 707 index patients with operated indirect congenital inguinal hernia (CIH) born in Budapest during the years 1962–1966 the frequency of CIH was two and five to six times higher, respectively, than in the general population. The rate of affected sibs was higher than that of parents but was greatly dependent on the sex of the index patient. Heritability estimates of CIH vary significantly in parents (0.35 ± 0.12) and in sibs (0.78 ± 0.14). In twins the heritability is 0.77. These data agree with the multifactorial threshold model involving dominance variance.
Dyggve‐Melchior‐Clausen syndrome: Genetic studies and report of affected sibs
Authors: Toledo S. P. A. , Saldanha P. H. , Lamego C. , Mourão P. A. S. , Dietrich C. P. , Mattar E.
Published: June 2005

We report a brother and sister with Dyggve‐Melchior‐Clausen dysplasia with mental retardation (MR) but as yet without spinal cord injury due to cervical spine abnormality. Mucopolysaccharide metabolism was studied in several ways and was found to be normal. Segregation analysis and study of consanguinity data confirm that both forms of the syndrome – that with MR, and that without MR (Smith‐McCort dysplasia) are rare autosomal recessives. Spinal cord injury and early death is a danger in both.
Familial, balanced insertional translocation of chromosome 7 leading to offspring with deletion and duplication of the inserted segment, 7p15 → 7p21
Authors: Miller Marvin , Kaufman Genevieve , Reed George , Bilenker Robert , Schinzel Albert
Published: June 2005

We report an uncle and niece with duplication and deletion, respectively, of segment 7p15 → 7p21 originating from a balanced, intrachromosomal insertion in their mothers. The proposita had prenatal and postnatal growth deficiency, retarded psychomotor development, microcephaly, wide cranial sutures, ocular hypertelorism, small palpebral fissures, apparently low‐set and malformed ears, cleft palate, congenital heart defect, hypoplasia of the distal phalanx of first fingers, rocker‐bottom feet, persistent cloaca, and imperforate anus. She died at three months. Her maternal uncle has duplication of this segment and is alive at 32 years. He has severe mental deficiency, but normal growth; communicating hydrocephalus was diagnosed at three months.
Osteopathia striata associated with familial dermopathy and white forelock: Evidence for postnatal development of osteopathia striata
Authors: Whyte Michael P. , Murphy William A. , Hermann Jürgen
Published: June 2005

Osteopathia striata and a macular, hyperpigmented dermopathy were found in a Caucasian woman and her two daughters. Sequential radiographs in one daughter showed that the bone lesions were not present during infancy but developed during early childhood. The skin lesions were not those most often associated with osteopathia striata, but appeared to be a unique dermatosis, which also included a hypopigmented forelock. A son had neither osseous nor ectodermal lesions. These abnormalities appear to represent a new syndrome, which is inherited with X‐linked or autosomal dominant transmission.
Acro‐renal‐mandibular syndrome
Authors: Halal Fahed , Desgranges Marie‐Françoise , Leduc Bernard , Thêorét Gilles , Bettez Paul
Published: June 2005

We report two female sibs, with severe split‐hand/split‐foot malformation associated with renal and genital anomalies. The patients also have severe mandibular hypoplasia and some other, minor anomalies. The relationship to the acro‐renal “syndrome” in particular and to other phenotypes with similar malformations in general is discussed. Because of consanguinity in the parents, autosomal recessive inheritance seems likely. However, the presence of a septate uterus in the mother and a double collecting system in the only living sib could also suggest possible dominant inheritance with variable expressivity.
The recurrence risk for neural tube defects in the United States: A collaborative study
Authors: Cowchock S. , Ainbender E. , Prescott G. , Crandall B. , Lau L. , Heller R. , Muir W. A. , Kloza E. , Feigelson M. , Mennuti M. , Cederquist L. , Karp Laurence E.
Published: June 2005

To determine the recurrence risk for patients with one prior pregnancy affected with neural tube defects (NTD), the authors have pooled date from eight testing centers. In 831 pregnancies studies because one sib was affected with an NTD, the recurrence rate was 3.0%, with 95% confidence limits of 2.0–4.3%, and 99% confidence limits of 1.8–4.8%. The recurrent lesion, whether spina bifida or anencephaly, tended to be concordant with the first to a significant degree. Only 12.2% or recurrent NTD were different from the first, with 95% confidence limits of 4.1–26.2%, and 99% confidence limits of 1.7–30.9%. Both an accurate recurrence risk and the information that a recurrent NTD lesion tends to be concordant with that in the first asffected child are useful in the genetic counseling of patients in the United States and in the selecton of appropriate prenatal diagnostic studies.
The G syndrome‐additional observations
Authors: Arya Sunita , Viseskul Chirane , Gilbert Enid F.
Published: June 2005

We are reporting the second lethal case of G syndrome occurring in a female. The developmental defects in this patient included posteriorly angulated auricles, bifid tip of tongue with a long frenulum, hypoplasia of the epiglottis and larynx, rocker bottom feet, and hypertrophied labia majora and clitoris. Additional anomalies not previously reported in the G syndrome were circumvallate placenta, and incompletely perforated hymen.
The meckel syndrome in the Hutterites
Authors: Schurig Verena , Bowen Peter , Harley Frances , Schiff David , Opitz John M.
Published: June 2005

At least three cases of the Meckel syndrome have been identified in the Hutterites. Two of these were sibs and were studied during life; the other, a close relative, was diagnosed retrospectively by a review of hospital records. All parents were consanguineous. The phenotype ranged in severity from the association of occipital meningocele, cystic kidneys, postaxial polydactyly, and microphthalmia to a milder expression consisting of cystic kidneys, ocular defects apparent only on funduscopic examination, and a brain abnormality demonstrated by computer tomography. Survival ranged from 5 to 13 months. In one patient, the renal lesion was manifested as a tubular rather than a glomerular defect, and was probably not the primary cause of death.
Anatomical analysis of the developmental effects of aneuploidy in man: The down syndrome
Authors: Bersu Edward T. , Opitz John M.
Published: June 2005

Detailed anatomical dissections of five Down syndrome (DS) bodies revealed a unique and consistent “internal phenotype” composed of: 1) variations in muscles, 2) peripheral artery variations, and 3) the presence of dilatations and nerve rootlets associated with the spinal accessory and first cervical nerves. Most of these variations may occur occasionally in the normal population, but their more frequent occurrence in the five DS cases provides further support for Shapiro's (1975) hypothesis that one effect of the extra autosome is to increase the instability of normal developmental processes.

Three of the variations: 1) the presence of an extra facial muscle, 2) multiple vertebral arteries, and 3) the presence of dilatations and nerve rootlets associated with the spinal accessory and 1st cervical nerves, may be the result of a failure of regression of otherwise transient embryonic structures.

A variation of the midfacial muscles of expression, explained as an arrest in development, has not been described previously and, to date, remains a manifestation unique to the trisomy 21 phenotype.

Aside from their use in developmental speculation, the sum of these variations may be useful for corroborating diagnoses of suspected post‐mortem cases of the DS without cytogenetic confirmation.
Renal hypodysplasia and unilateral ovarian agenesis in the Penta‐X syndrome
Authors: Toussi Tahmouresse , Halal Fahed , Lesage Robert , Delorme Fernand , Bergeron André , Opitz John M.
Published: June 2005

We report the case of a 3‐year‐old penta‐X female with two previously undescribed anomalies: hypoplastic kidney and absent ipsilateral ovary. The gross and histologic structure of the contralateral ovary was normal, suggesting that adults with this syndrome may be fertile.
Gardner syndrome and periampullary malignancy
Authors: Pauli Richard M. , Pauli Mary E. , Hall Judith G. , Opitz John M.
Published: June 2005

In a family with colonic polyposis and the typical associated findings of Gardner syndrome (osteomas and soft‐tissue tumors), two and possibly four of the affected members developed periampullary malignancy. A review indicates that individuals with Gardner syndrome may have a 100‐ to 200‐fold increased risk of developing periampullary carcinoma when compared to the general population. While certain families and certain individuals (those with other duodenal involvement, males and those with all of the characteristics of Gardner syndrome expressed) may be most susceptible, all patients with Gardner syndrome should be periodically endoscopically evaluated for the presence of upper gastrointestinal tract disease.
Linkage studies in spinocerebellar ataxia (SCA)
Authors: Morton N. E. , Lalouel J‐M. , Jackson J. F. , Currier R. D. , Yee S.
Published: June 2005

Data are now available on 9 pedigrees in detail and 4 pedigrees as lod scores only. Linkage to HLA is significant (Ž = 5.53 at recombination rates of 0.223 in males and 0.327 in females). Tight linkage is excluded. Nine pedigrees which appear to be typical olivopontocerebellar atrophy (OPCA I) have recombination rates of 0.150 in males and 0.300 in females. The remaining 4 pedigrees are clinically atypical or include discrepant data and give no evidence for linkage. The symbol SCA1 is proposed for a locus on chromosome 6 (loosely linked to HLA), at which at least one allele produces OPCA I (Menzel type). It is not yet clear whether other clinical types are determined by alleles at different loci, although this is suggested by several pedigrees, including a Danish pedigree of OPCA with dementia. Linkage evidence will be decisive in delineating the ataxias.
A family with three recessive traits and homozygosity for a long 9qh+ chromosome segment
Authors: Christian Joe C. , Dexter R. N. , Palmer C. G. , Muller J.
Published: June 2005

We report a family in which a mentally retarded, proportionately dwarfed girl had a child from a presumably incestuous mating that had the Ellis van‐Creveld syndrome, presumed autosomal recessive hydrocephalus (Dandy‐Walker type), and homozygosity for an extremely long 9qh+ chromosomal marker.

The mentally retarded mother had normal birth weight, unusual facial appearance, and virtual absence of secondary sexual hair; she developed severe hypoglycemia during pregnancy. Her parents were first cousins, and she may have a previously unreported autosomal recessive syndrome.
Duplication 11p11.3 → 14.1 to meiotic crossing‐over
Authors: Strobel Richard J. , Riccardi Vincent M. , Ledbetter David H. , Hittner Helen M. , Francke Uta
Published: June 2005

An infant with macular dysfunction, cleft lip and palate, and developmental delay was shown to have an inverted duplication of 11p11.3→p14.1 on the basis of meiotic recombination subsequent to an intrachromosomal “shift” in his mother. A half‐sister had previously been shown [3] to have the reciprocal recombinant with resultant deletion of 11p11.3→11p14.1.
Evidence of genetic variation for α‐N‐acetyl‐D‐glucosaminidase in black and white populations: A new polymorphism
Authors: Vance J. M. , Pericak‐Vance M. A. , Elston R. C. , Conneally P. M. , Namboodiri K. K. , Wappner R. S. , Yu P. L. , Optiz John M.
Published: June 2005

Serum and/or plasma samples from 360 Whites and 126 Blacks were assayed for activity of the lysosomal hydrolase α‐N‐acetyl‐D‐glucosaminidase (NAG). The samples from the Blacks had an increased mean (0.50 nm/ml/min) and standard deviation (0.30 nm/ml/min) compared to those from the Whites (0.29 nm/ml/min and 0.10 nm/ml/min, respectively). After loge transformation and admixture analysis, it was possible to demonstrate the presence of 3 distributions of NAG activity in Blacks and at least 2 in Whites. Segregation analysis of the NAG activity of 29 White half‐sib twin families indicated that a genetic model for the inheritance of NAG activity provided a better fit (P < 0.01) with the data than the “environmental” model. Thus, the study suggests the presence of a genetic polymorphism for NAG activity in Black and White populations. The presence of alleles for high and low NAG activity in the normal population could lead to incorrect interpretation of serum carrier tests for Sanfilippo syndrome, type B.
Genetic diseases in Lebanon
Authors: Der Kaloustian Vazken M. , Naffah Josette , Loiselet Jacques , Optiz John M.
Published: June 2005

Lebanon has a high incidence of common and rare genetic diseases, due probably to the mosaic different ethnic origins and the high rate of consanguineous marriages in certain communities.

Two major investigations, exploring the genetic structure of the Lebanese population, indicated the population to be caucasiods (though Oriental traits were found). These investigations involved studies of dermatoglyphics, and type and distribution of genetic markers and protein variants.

Recorded genetic diseases, some characteristic of ethnic group or particular to a geographic region include familial paroxysmal polyserositis, familial hypercholesterolemia, hypothroidism, the Dyggve‐Melchoir‐Clausen syndrome, Sandhoff disease, and various genetic hematologic diseases.

Genetic counseling and care to patients with genetic diseases is available in Beirut from the Faculty of Medicine at American University and St. Joseph University. Also, the Lebanese National Council for Scientific Research initiates and finances medical genetics programs.
Holoprosencephaly and endocrine dysgenesis in brothers
Authors: Begleiter Michael L. , Harris David J. , Optiz John M.
Published: June 2005

We report 2 brothers with holoprosencephaly, endocrine dysgenesis, and micropenis. This combination has been reported once previously in sibs (2 sisters) by Hintz et al (1968). In that case, autosomal recessive inheritance may have been the cause. The same may be true in our patients, but X‐linked recessive inheritance is not excluded.
Ring chromosome 2 in a child with growth failure and few congenital abnormalities
Authors: Vigfusson Norman V. , Kapstafer Kennard J. , Lloyd Marilyn A. , Optiz John M.
Published: June 2005

A ring chromosome 2 mosaic [46,XX/46,XX,r(2)(p25q37)] was found in a newborn female with severe intrauterine growth retardation (IUGR), postnatal growth failure, and a few minor abnormalities. Psychomotor development has been normal to 19 months old. A ring chromosome 2 is present in 77.8% of the nuclei examined and is not found in the parents or a sibling. G‐ and R‐banding reveal the break points to be p25q37. The presence of a normal cell line indicates that the chromosome abnormality arose after conception.
Nonspecific X‐linked mental retardation I: A review with information from 24 new families
Authors: Herbst Diana S. , Optiz John M.
Published: June 2005

Clinical manifestations and other aspects of nonspecific X‐linked mental retardation are reviewed using data from the literature and information on affected males in 24 new families ascertained in British Columbia. A great degree of variability was apparent in the mental abilities of affected males. Speech defects, other CNS disorders and minor physical changes such as “big” ears or a highly arched palate were not present in many cases. Evidence for the existence of a clinical entity of mental retardation associated with the fragile site at Xq27 or 28 and macro‐orchidism is discussed. Genetic phenomena of reduced penetrance in males and of partial expression in females with respect to X‐linked recessive genes are examined. Consideration is given to the question of whether this type of mental retardation is due to X‐linked recessive or autosomal dominant sex‐limited genes. Most ascertained cases of X‐linked mental retardation are from families of northern European extraction. Recommendations are made regarding the diagnosis and counseling of X‐linked mental retardation cases.
The estimation of phenotype distributions from pedigree data
Authors: Winter Robin M. , Optiz John M.
Published: June 2005

A method is described to estimate from pedigree data the probability density function of a quantitative phenotype, given a specific genotype. Theoretically, pedigrees of any size or complexity that are segregating for conditions of known Mendelian inheritance can be used. Under certain circumstances, the estimates are unbiased by the method of ascertainment.
Coloboma‐hypospadias
Authors: Halal Fahed , Farsky Katarina , Opitz John M.
Published: June 2005

We report a five‐year‐old boy with bilateral ocular coloboma, hypertelorism, hypospadias, and mental retardation. The father has hypertelorism and a deceased sibling had unilateral iris coloboma. This observation may represent (1) the BBB syndrome with coincidentally segregating coloboma; (2) discovery of coloboma as a new but rare component manifestation of the BBB syndrome; or (3) a new autosomal dominant pleiotropic syndrome.
Idiopathic hydrops fetalis report of 4 patients including 2 affected sibs
Authors: Schwartz Sheldon Miles , Viseskul Chirane , Laxova Renata , McPherson Elspeth W. , Gilbert Enid F. , Opitz John M.
Published: June 2005

We report four patients with idiopathic hydrops fetalis (IHF), two being affected sibs; the latter represent the first reported familial occurrence. A review identified 45 additional cases that seem to represent 1/3 to 2/3 of all cases of hydrops fetalis of nonimmunologic origin (NIHF). Our patients and the other adequately documented cases permit delineation of “idiopathic” fetal hydrops; ie, that form of the condition which is not associated with any detectable fetal or maternal disorders. These fetuses are usually premature, often the product of a gestation complicated by pre‐eclampsia, occasional maternal anemia, and most often polyhydramnios. The fetuses have striking edema of most tissues with effusions into serous cavities, but no other specific anatomic abnormalities. They are often hypoproteinemic, but not anemic and do not manifest signs of accelerated hematopoiesis. Results of fetal and maternal immunohematological examination are normal. Fetal mortality rates approach 100% but recent data suggest that salvage rates can be significantly improved with early diagnosis. This requires accurate diagnosis and all factors and conditions known to be associated with other types of NIHF should be excluded. A relationship between fetal hypoalbuminemia and IHF may exist and needs further investigation. IHF is sporadic in most instances; however, recessive inheritance may be indicated by occurrence in two sibs. IHF represents a distinct, frequently unrecognized and relatively common entity in need of further study and increased recognition.
Deletions of different segments of the long arm of chromosome 4
Authors: Mitchell Joyce A. , Packman Seymour , Loughman William D. , Fineman Robert M. , Zackai Elaine , Patil Shivanand R. , Emanuel Beverly , Bartley James A. , Hanson James W. , Opitz John M.
Published: June 2005

We report the clinical and chromosomal findings in 8 patients with deletions of the long arm of chromosome 4. Four of these patients appear to have terminal deletions beginning in band 4q31, and therefore, lack the digital 1/3 of the long arm of chromosome 4. We confirm that deletion of 4q31→qter causes a recognizable syndrome, and we further define the phenotype of that syndrome. A 5th patient has a shorter terminal deletion, ie, 4q33→qter. This deletion causes a milder phenotypic expression than that seen in the severe 4q terminal‐deletion syndrome. The remaining 3 patients have interstitial deletions of the long arm of the 4th chromosome, including segments 4q21.1→q25, 4q21.3→q26, and 4q27→q31.3. The phenotypic expression noted in these patients is variable and differs from the 4q terminal‐deletion syndrome.
The King syndrome: Malignant hyperthermia, myopathy, and multiple anomalies
Authors: McPherson Elspeth W. , Taylor Claude A. , Opitz John M.
Published: June 2005

Heterogeneity in malignant hyperthermia is being recognized with increasing frequency. In 1973, King described a subgroup of malignant hyperthermia patients with slowly progressive myopathy, short stature, kyphoscoliosis, pectus carinatum, cryptorchidism, and a characteristic facial appearance. Seven cases have been reported, all in males. We present the case of a girl with similar clinical findings who died in a malignant hyperthermia crisis and review the previously reported cases of King syndrome. The delineation of King syndrome provides further evidence for the heterogeneity of malignant hyperthermia and increases awareness of this disorder; its recognition in a female may lead to preoperative diagnosis and prevention of malignant hyperthermia crisis in King syndrome patients.
Psychosocial aspects of patients with the Ullrich‐Turner syndrome
Authors: Chen Harold , Faigenbaum David , Weiss Harold , Opitz John M.
Published: June 2005

Family and social background and psychosexual and psychomotor development were studied on 24 patients with the Ullrich‐Turner syndrome ranging in age from 9 months to 18 years. Infancy is often characterized by mild feeding problems and sleeping difficulty. Early motor development is normal or mildly delayed but acquisition of speech and toilet training appear to be appropriate for age. Social skills are excellent. Psychopathology is not a significant aspect of the Ullrich‐Turner syndrome. Psychological tests support the findings of verbal IQ exceeding performance IQ, space‐form perceptual deficits, and visual motor deficit. No difference of intelligence was found between apparently nonmosaic and mosaic types of Ullrich‐Turner syndrome. The degree of parental understanding and appropriate attitudes toward the patient and the syndrome largely depend on good family relationships, the socieconomic level of the family, parents' personalities and their ability to cope with the implications of the syndrome, and appropriate physician's counseling.
Early recognition of the Coffin‐Lowry syndrome
Authors: Wilson William G. , Kelly Thaddeus E. , Opitz John M.
Published: June 2005

We report a 2‐year‐old male infant with the Coffin‐Lowry syndrome, and describe the change in his clinical and radiographic manifestations during the first 2 years of life. Review of published cases of the Coffin‐Lowry syndrome indicates that these manifestations are progressive, and that all of the associated characteristics may not be apparent in early childhood. The importance of continued evaluations of these patients and examination of relatives for mild manifestations is emphasized.
Multiple congenital anomalies, thymic dysplasia, severe congenital heart disease, and oligosyndactyly with a deletion of the short arm of chromosome 5
Authors: Taylor M. J. , Josifek K. , Opitz John M.
Published: June 2005

A female infant was born at term with congenital anomalies and a deletion of the short arm of chromosome 5. The anomalies included thymic dysplasia and lymphocyte‐depleted nodes of the type seen in combined immune deficiency; atrial and ventricular septal defects, pulmonary valve atresia, and anomalous pulmonary‐bronchial communication through the lungs; and shortness of forearms with syndactyly of fingers. A review indicates that the association of cardiac lesions, thymic dysplasia, oligosyndactyly and deletion of chromosome 5p is unique.
Autosomal dominant late adult spinal muscular atrophy, type finkel
Authors: Richieri‐Costa A. , Rogatko A. , Levisky R. , Finkel N. , Frota‐Pessoa O. , Opitz John M.
Published: June 2005

We describe clinical and genetic data from the study of two families with 80 members affected with the autosomal dominant, slowly progressive spinal muscular atrophy of late onset (average 48.8 years), first described by Finkel in 1962. Electromyography and muscle biopsy of a number of patients confirmed the neurogenic nature of the condition. Unusual findings in this disorder were cramps, spontaneous fits of suffocation, and symptomatic myotonia. Other manifestations are slow loss of muscle strength and progressive proximal atrophy, which starts in the lower limbs and progresses to the upper limbs; hypoactive or absent tendinous reflexes; and generalized fasciculations. Sensory and cranial nerve function is unimpaired. Probabilities for genetic counseling are evaluated by means of a method adequate to the late‐onset nature of the condition.
Further delineation of the C (trigonocephaly) syndrome
Authors: Antley Ray M. , Hwang Do Sung , Theopold W. , Gorlin Robert J. , Steeper T. , Pitt David , Danks David M. , McPherson Elspeth , Bartels H. , Wiedemann H.‐R. , Opitz John M. , Herrmann Jürgen
Published: June 2005

This communication brings the number of recognized cases of the C (trigonocephaly) syndrome to 11. The pattern of findings includes an anomaly of the anterior cranium and frontal cortex (trigonocephaly), the root of the nose (broad nasal bridge, epicanthus, and short nose), and palate (thick anterior alveolar ridges); abnormalities of the limbs (polysyndactyly, bridged palmar creases, short limbs, and joint dislocations and/or contractures); visceral defects (congenital heart defects, cryptorchidism, and abnormal lobulations of the lungs and kidneys). Auricular, mandibular, skin, and genital abnormalities also occur. Consistent neurological findings are hypotonia, strabismus, and psychomotor retardation; seizures have been reported. Normal chromosomes, normal parents with multiple affected offspring, equal sex ratio of affected individuals, and consanguineous matings all support autosomal recessive inheritance of the C syndrome. In autopsied cases, there has been a suggestion of defective central nervous system myelination. About ½ of the cases have died within the first year. All survivors have severe to profound mental retardation except for one child who has moderate retardation.
46, XX, del (18p) with amenorrhea, hypothyroidism, and ptosis
Authors: Stoffer Sheldon S. , Koen Anna L. , Abbasi Ali A. , Brown Saul , Opitz John M.
Published: June 2005

A 17‐year‐old girl was initially evaluated because of primary amenorrhea and lack of sexual development. Chromosome studies demonstrated the presence of 46, XX, del (18p). The patient is now 21 years old and still has not menstruated. This is the first reported case of 46, XX, del (18p) presenting with primary amenorrhea. The case is of additional interest in that ptosis, a common finding in this syndrome, was not present at birth but was first noted at age 9.
Progressive spastic paraparesis, vitiligo, premature graying, and distinct facial appearance: A new genetic syndrome in 3 sibs
Authors: Lison Michael , Kornbrut Benjamin , Feinstein Avraham , Hiss Yehuda , Boichis Haim , Goodman Richard M. , Opitz John M.
Published: June 2005

We describe progressive spastic paraparesis of the lower limbs in the presence of generalized vitiligo, premature graying of body hair, and distinct facial appearance in 3 sibs whose parents are first cousins. The condition is considered an autosomal recessive trait. The pathogenesis of this neurocutaneous disorder is unknown.
Familial cutaneous amyloidosis with systemic manifestations in males
Authors: Partington M. W. , Marriott P. J. , Prentice R. S. A. , Cavaglia A. , Simpson N. E. , Opitz John M.
Published: June 2005

We describe a family in which two males and seven females have brown pigmentation of the skin. In the females, the type and distribution of the pigmentation mimicked incontinentia pigmenti; in the males, the pattern was reticulate. The histological appearance was the same in both sexes with amyloid deposits in the papillary dermis, melanin in the basal layer, and slight hyperkeratosis. The females were otherwise normal. Both males had thrived poorly as infants but had survived. One had severe gastroenteritis with blood in the stools starting at the age of three weeks followed by seizures, hemiplegia, and developmental delay; the other had recurrent pneumonia throughout life, a urethral stricture, inguinal herniae, and near‐blindness from amyloid deposition in the cornea.

Five other males in the family had had severe illnesses. Two died of pneumonia by three months. One died at three months from colitis. Both remaining boys had colitis as infants, failed to thrive, and developed recurrent pneumonia from which one died at three years.

We think all of these relatives had the same disease carried by a single gene with pleiotropic effects. The most likely form of inheritance is X‐linked.
Genetics of cerebrotendinous xanthomatosis (CTX): An autosomal recessive trait with high gene frequency in Sephardim of Moroccan origin
Authors: Berginer Vladimir M. , Abeliovich Dvorah , Opitz John M.
Published: June 2005

We describe 6 patients (from 3 families) affected with cerebrotendinous xanthomatosis (CTX). All are Sephardic Jews of Moroccan extraction. In view of the small number of CTX patients diagnosed in the world (a total of 50 including our 6 patients), we are probably dealing with an ethnic subgroup with a high CTX gene frequency, which we have estimated to be 1/108. Since there are differences in expression in this disease, we recommend cholestanol study in cases of undiagnosed cataract or tendinous xanthomas in childhood or early adolescence. The diagnosis in CTX is important not only for genetic counseling, but also in view of possible treatment.
The dup(17p) syndrome
Authors: Feldman G. M. , Baumer J. G. , Sparkes R. S.
Published: June 2005

In a 42‐month‐old girl a duplicated 17p chromosome anomaly was identified by trypsin‐Giemsa banding techniques. The clinical findings are compared with those of previous case reports. Common phenotypics changes include failure to thrive; hypoplastic, apparently low‐set ears; micrognathia; flexion abnormalities of fingers; and foot abnormalities.
Langer–Giedion syndrome with interstitial 8q–deletion
Authors: Zabel Bernhard U. , Baumann Walter A. , Opitz John M.
Published: June 2005

We describe a 12‐year‐old girl with Langer‐Giedion syndrome (tricho‐rhino‐pha‐langeal syndrome type II) who also had vertebral malformations. Chromosome analysis identified an interstitial del(8q): 46,XX,del(8)(pter→q22::q234→qter) as a cause of this syndrome.
Syndactyly type V
Authors: Robinow Meinhard , Johnson G. Frank , Broock Gerald J. , Opitz John M.
Published: June 2005

We report a mother and three of her four children with type V syndactyly. All the patients had metacarpal 4–5 fusion. The other hand anomalies consisted of abnormal origin of the fifth fingers, anomalies of digits 4 and 5, brachydactyly, syndactyly, camptodactyly, absent distal interphalangeal creases, and unusual palmar dermatoglyphics. Anomalies of the feet consisted of varus deviation of the metatarsals, valgus deviation of the toes, hyperplasia of the first ray, and hypoplasia of the third to fifth rays. None of the patients had metatarsal fusions. The anomalies were similar in the mother and her two older sons far less severe in her daughter. This daughter also had a congenital anomaly of the urinary tract. Anomalous and/or defective muscle and tendon insertions were demonstrated in one patient during an operation. Syndactyly V is transmitted as an autosomal dominant trait.
Studies of microcephalic primordial dwarfism II: The osteodysplastic type II of primordial dwarfism
Authors: Majewski F. , Ranke M. , Schinzel A. , Opitz John M.
Published: June 2005

We describe three unrelated patients with intrauterine growth retardation (IUGR) and nearly identical bone changes. In certain respects, they share similarities with the Seckel syndrome: small forehead, moderately prominent nose, micrognathia, pronounced intrauterine and postnatal growth retardation, microcephaly, and mental retardation. Differences from the Seckel syndrome include disproportionate shortness of forearms and legs in the first years of life, brachymesophalangy, brachymetacarpy I, V‐shaped flare of at least the distal femoral metaphyses, triangular shape of the distal femoral epiphyses, a high and narrow pelvis, proximal femoral epiphysiolysis, and coxa vara. Hormone studies in two cases demonstrated no gross disturbances, especially no deficit of hGH and somatomedin. Two previously reported cases referred to as Seckel syndrome had nearly identical bone changes. The cause of this “new” type of IUGR remains unclear.
A cost‐benefit analysis of prenatal diagnosis for neural tube defects selectively offered to relatives of index cases
Authors: Sadovnick A. D. , Baird P. A. , Opitz John M.
Published: June 2005

Relatives of patients with neural tube defects (NTD) frequently request prenatal diagnosis for this problem, and it would be helpful to have information on cost‐benefit aspects of offering this service to them.

A cost‐benefit analysis was done for selective prenatal diagnosis offered to parents and aunts of index cases as these are the two groups for which adequate empiric data are available. The results are extrapolated to other relatives.

The study concludes that prenatal diagnosis is cost‐beneficial if selectively offered for pregnancies where the fetus is a first or second degree relative of an index case. The results are discussed in terms of whether prenatal diagnosis should be offered to all aunts of index cases or only to maternal aunts.

The lifetime costs of caring for an individual with spina bifida, in 1980 dollars, was calculated to be approximately $84,000.
Studies of malformation syndromes of humans XXXIIIC: The FG syndrome — further studies on three affected individuals from the FG family
Authors: Opitz John M. , Kaveggia Elizabeth G. , Adkins William N. , Gilbert Enid F. , Viseskul Chirane , Pettersen James C. , Blumberg Bruce , Herrmann Jürgen
Published: June 2005

The brain findings at autopsy of an 18‐year‐old male with FG syndrome were megalencephaly, midline fusion of mammillary bodies, heterotopia of neuroglial tissue in the 7th and 8th nerves, and ependymal cell replacement by neuroglial tissue as well as a diffuse defect of neuronal cell migration evidenced from pachygyria of many gyri, dysgenesis of cerebral cortex, and heterotopia of neurons in the white matter of the centrum ovale. A cousin, studied at 20 weeks' gestational age, had gross turridolichocephaly with enlarged cranium and also multiple minor external and internal anomalies. An affected brother of this fetus died at 17 months of complications of a congenital heart defect and CNS dysfunction. X‐linked inheritance of the FG syndrome is confirmed.
Ring chromosome 17 in a mentally retarded young man—clinical, cytogenetic, and biochemical investigations
Authors: Chudley Albert E. , Pabello Paulino D. , McAlpine Phyllis J. , Nickel Barbara E. , Shokeir M. H. K. , Opitz John M.
Published: June 2005

A young, mentally retarded man with seizures was discovered to have a ring chromosome 17. He had no major anomalies. The phenotype associated with r(17) probably is variable. The patient's deletion and genotype allowed us to reduce further the chromosome location of the acid α‐glucosidase gene.
Male to male transmission of cerebral gigantism
Authors: Halal Fahed
Published: June 2005

We report three individuals (two brothers and their father) with cerebral gigantism. All three had striking macrocephaly, large birth weight, gigantism, and variaable degrees of psychomotor retardation. Other findings included abnormal dermatoglyphics and an unusual metacarpophalangeal pattern profile in two of the three. To our knowledge, this is the first family with documented male to male transmission of cerebral gigantism.
Chondrodystrophic myotonia (schwartz‐jampel syndrome): Report of a new case and follow‐up of patients initially reported in 1969
Authors: Edwards William C. , Root Allen W. , Opitz John M.
Published: June 2005

We report on a 9‐year‐old boy with chondrodystrophic myotonia (Schwartz‐Jampel syndrome) and the progress of a brother and sister with this syndrome first described in 1969. This is an autosomal recessive trait characterized by mask‐like face, narrow palpebral fissures (due to blepharophimosis, blepharospasm, and abnormal orbital configuration), microstomia, micrognathia, myotonia, muscular hypertrophy, osteochondrodysplasia, and growth retardation. Expressivity varies and in some sibships females are less severely affected than their brothers. The sexual development of the sibs with chondrodystrophic myotonia, who are now in the mid to late second decade, has been normal. Linear growth rate accelerated during puberty but the adult height of the male is less than normal. Administration of human growth hormone had no consistent effect on the growth pattern of this boy.
Limb deficiency and splenogonadal fusion
Authors: Pauli Richard M. , Greenlaw Ann
Published: June 2005

We report a 10‐year‐old boy with tetramelic limb deficiencies, splenogonadal fusion, and mild mandibular and oral abnormalities. This patient is quite typical of 14 reported cases with this combination of findings. This association must be nosologically closely related to the Hanhart syndrome and other syndromes of limb deficiency and orofacial abnormalities. Recent experience does not support the idea that limb reduction with splenogonadal fusion is an invariably lethal dominant disorder.
The effect of parental age on rate of mutation for duchenne muscular dystrophy
Authors: Yasuda Norikazu , Kondo Kiyotaro , Opitz John M.
Published: June 2005

The effect of parental age on mutation rates at the Duchenne Muscular Dystrophy (DMD) locus was studied in 514 male probands who constitute two thirds of the known patients in Japan. We were unable to detect an effect of maternal age at birth of proband or maternal grandfather's age at birth of the mother of the proband on the rate of DMD mutations. The result supports an observation on the hemophilia gene.
Phenotypic heterogeneity in cystic fibrosis
Authors: Sing Charles F. , Risser David R. , Howatt William F. , Erickson Robert P.
Published: June 2005

We have confirmed heterogenity in CF using a different combination of primary clinical variables than those used in previous studies. Subgroupings of individuals with similar levels of sweat chloride were independent of the clustering based on level of pancreatic enzyme supplementation and degree of pulmonary involvement. Data from families with multiple CF children are consistent with the hypothesis that the genetic etiology of CF involves two or more genes that modify the expression of the primary gene defect.
Identical male twins and brother with Cockayne syndrome
Authors: Houston C. Stuart , Zaleski Witold A. , Rozdilsky Bohdan , Opitz John M.
Published: June 2005

The clinical, radiological, and neuropathological findings in early onset Cockayne syndrome are illustrated in identical twins and their brother. Their appearance of dwarfism with small head and prominent beaked nose strongly resembled that seen in the Seckel syndrome, but unlike patients with that syndrome they had a normal birth weight (for twins), thick cranial vaults, intracranial calcification, and a severe degree of mental retardation. The twins were deaf and blind, with optic atrophy and retinal pigmentation, while their brother had cataracts.

Their hands and feet were large in proportion to their small trunk. They had cutaneous sensitivity to any slight exposure to ultraviolet light and severe neurologic problems with incoordination and spasticity. Radiologic findings included microcephaly, a thick cranial vault, a small pelvis, coxa valga, and “ivory epiphyses” in terminal phalanges of hands and feet. Pathologic findings included atrophy of white matter with widespread patchy demyelination, and massive siderocalcific deposits in the brain, particularly in the basal ganglia and cerebellum. While autosomal recessive inheritance is most likely, formally X‐linked inheritance cannot be excluded.
The Angelman syndrome in two brothers
Authors: Pashayan Hermine M. , Singer William , Bove Catherine , Eisenberg Ellen , Seto Boon
Published: June 2005

We report two brothers with the Angelman syndrome. With the exception of the reports by Kuroki et al, all previously reported cases were sporadic. Overall sex ratio is M1:F1. Genetic heterogeneity may be present. Further data are required to determine emperic recurrence risks after a first occurrence in a family. A few cases may be due to autosomal or X‐linked recessive inheritance. No chromosome abnormality has been found to date.
Deletion of the long arm of chromosome 11, [del(11)(q23)]
Authors: Monteleone Patricia L. , Chen Su‐Chiung , Nouri‐Moghaddam Soraya , Blair John D. , Tietjens Michael , Opitz John M.
Published: June 2005

We report sporadic occurrence of deletion of the long arm of chromosome 11 (q23 ⇀ qter) in a male newborn infant with intrauterine growth retardation, craniofacial, cardiac, and orthopedic abnormalities and neonatal death but without genital abnormalities. This deletion is seen predominantly in females; here we emphasize the importance of an XX sex chromosome constitution as a factor determining phenotypic expression of and survival in the del(11q) syndrome. We also provide a description of the cardiovascular system from postmortem examination. The cardiac findings are similar to those of two previously autopsied cases and will assist in early clinical diagnosis of the 11q‐syndrome.
Pachyonychia Congenita (Jadassohn‐Lewandowsky syndrome): A seventeen‐member, four‐generation pedigree with unusual respiratory and dental involvement
Authors: Stieglitz J. B. , Centerwall W. R. , Opitz John M.
Published: June 2005

Pachyonychia Congenita (PC) is an autosomal dominant syndrome of thick nails and other epithelial defects. A hospitalization for severe respiratory distress in a 3‐year‐old boy with PC and an affected father led to the discovery of 17 affected persons in a kindred spanning four generations. Nine relatives had varying degrees of upper respiratory tract obstruction, and eleven had dental aberrations.

We review PC and discuss other unusual findings in this kindred, ie, arthritis in four affected relatives and a discrepancy between expected and observed ratios of affected to unaffected offspring of mothers with PC.
Ring‐11 chromosome: Phenotype‐karyotype correlation with deletions of 11q
Authors: Cousineau Anthony J. , Higgins James V. , Scott‐Emuakpor Ajovi B. , Mody Gita , Opitz John M.
Published: June 2005

The cytogenetic evaluation of a female infant with congenital anomalies led to the identification of the second reported case of a ring‐11 chromosome. Unlike the previously described case, in which the patient had only minimal clinical findings and no demonstrable loss of material from the ring, our patient had numerous anomalies that were asssociated with a substantial deficiency of 11q material. The different phenotypes in these two cases represent variation in the amount and location of the chromosomal material lost during the genesis of the ring.

The manifestations of this patient and the deletion of region q24→qter from the ring‐11 identify a specific chromosome deletion syndrome referred to as del (11q) syndrome.
Duplication of 16p from insertion of 16p into 16q with subsequent duplication due to crossing over within the inserted segment
Authors: Cohen Maimon M. , Lerner Cynthia , Balkin Nancy E.
Published: June 2005

Two members of a large family had a similar multiple congenital anomalies mental retardation (MCA/MR) syndrome and an identical aberration of chromosome 16. Their mothers, who are first cousins, had a different abnormality of one chromosome 16, which appeared to be an acrocentric. We interpret these findings as an insertion of a segment of 16p into 16q, following a three‐break rearrangement and meiotic crossing over. The two abnormal children have a duplication of 16p11→p13. The clinical manifestations of these patients differ from those of previously reported cases of dup(16p).
Radial ray aplasia and renal anomalies in father and son: A new syndrome
Authors: Sofer Shaul , Bar‐Ziv Jacob , Abeliovich Dvorah
Published: June 2005

We describe a father and his son with bilateral absence of radius and thumb. Both have short stature, external ear malformation, and renal anomaly. In the son a high frequency of chromosome breaks in lymphocytes was found.

We compare this familial syndrome to Fanconi anemia and other radial ray aplasia syndromes and conclude that we are dealing with a different entity, which apparently is inherited as a dominant trait.
Search for a red cell enzyme or serum protein marker in amyotrophic lateral sclerosis and parkinsonism‐dementia of guam
Authors: Blake N. M. , Kirk R. L. , Wilson S. R. , Garruto R. M. , Gajdusek D. C. , Gibbs C. J. , Hoffman P. , Opitz John M.
Published: June 2005

Frequency distributions were determined for 24 red cell enzyme and four serum protein systems, in an attempt to identify a genetic marker associated with either amyotrophic lateral sclerosis (ALS) or parkinsonism‐dementia (PD), two progressive and fatal neurological disorders of unknown cause found with unusually high incidence among the Chamorros of Guam and the Northern Mariana Islands. No striking associations were identified between either disorder and any of the gene markers tested. Thus, no genetic cause is known for either disease; local environmental factors are most likely involved in pathogenesis.
Progressive hemifacial atrophy (Parry‐Romberg syndrome) report with review of genetics and nosology
Authors: Lewkonia R. M. , Lowry R. B. , Opitz John M.
Published: June 2005

We describe a boy with mild hemifacial atrophy (Parry‐Romberg syndrome); he had localized scleroderma on a leg and his trunk, and antinuclear antibodies in his serum. These findings support suggestions that this disorder could be a variant of localized scleroderma rather than a developmental anomaly or dysplasia. A review of the literature does not support assertions of autosomal dominant inheritance of the condition.
First report of mosaic trisomy 12 in a liveborn individual
Authors: Patil Shivanand R. , Bosch E. Peter , Hanson James W.
Published: June 2005

Trisomy 12 mosaicism was found in a 36‐year‐old woman with minor anomalies, neuromuscular abnormalities, and moderate mental retardation. Trisomy 12 was present in 13% of the lymphocytes but not in skin fibroblasts. Previous reports of dup (12p) and dup(12q) are reviewed. To our knowledge this is the first report of a “complete” trisomy 12 in a liveborn individual.