RESUMO
Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 22 , Heterogeneidade Genética , Hipertelorismo/genética , Cromossomo X , Pré-Escolar , Feminino , Ligação Genética , Humanos , Hipospadia/genética , Escore Lod , Masculino , Linhagem , SíndromeRESUMO
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.
Assuntos
Displasia Ectodérmica/genética , Genes Dominantes , Adolescente , Doenças das Glândulas Suprarrenais/genética , Adulto , Cistos/genética , Feminino , Humanos , Masculino , Unhas Malformadas/genética , Mamilos/anormalidades , Anormalidades Dentárias/genéticaRESUMO
We report on a 5-year-old girl with a progeroid disorder and compare her to a previously reported woman now in her forties, whom she resembles to a striking degree. Common manifestations include pre- and post-natal growth retardation, markedly diminished subcutaneous fat, wrinkled skin, abnormally scant hair growth, hypoplastic distal phalanges with hypoplastic nails, umbilical hernia, large open anterior fontanelle, and normal cognitive and motor development. Both patients have had a prematurely aged appearance since birth. These 2 patients appear so different from previously reported patients with progeroid disorders that they may represent a separate entity.
Assuntos
Progéria/congênito , Anormalidades Múltiplas , Adulto , Feminino , Transtornos do Crescimento/complicações , HumanosRESUMO
We describe an infant boy with a unique de novo translocation involving chromosomes 1 and 4, resulting in dup(4q) and del(1p). His karyotype was 46,XY,-1,+der(1)t(1;4) (p36.2;q31.2). He had minor anomalies, congenital heart defect, respiratory distress, seizures, and central nervous system abnormalities. He died at age 11 weeks. The patient had manifestations of dup(4q) del(1p), and he was more seriously affected than patients having only one of these. No other patient with an identical chromosomal finding has been reported.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas/genética , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 4 , Translocação Genética , Transtornos Cromossômicos , Evolução Fatal , Cardiopatias Congênitas/genética , Humanos , Recém-Nascido , MasculinoRESUMO
A 19-year-old patient with Williams syndrome and renal cystic dysplasia is presented. This young man has had gradual deterioration of renal function and recurrent, acute episodes of dehydration secondary to a concentrating defect. A review revealed several reports of renal dysfunction in patients with Williams syndrome, but this complication has not been sufficiently emphasized. We recommend that all patients with Williams syndrome undergo periodic ultrasound examination and renal function evaluation.
Assuntos
Falência Renal Crônica/diagnóstico , Doenças Renais Policísticas/diagnóstico , Adolescente , Coartação Aórtica/diagnóstico , Face/anormalidades , Humanos , Deficiência Intelectual , Masculino , Síndrome , UltrassonografiaRESUMO
Dubowitz syndrome is an autosomal recessive disorder of growth retardation, characteristic face, mild mental retardation, and eczema originally described by Dubowitz [1965]. Little information is available on natural history and adulthood in this disorder. We report on a 30-year-old woman who was one of the first patients to be diagnosed with the condition [Grosse et al., 1971, Z Kinderheilkd 110:175-187]. Microcephaly, short stature, leg length discrepancy, hyperextensible joints, spina bifida occulta, and absence of anterior cruciate ligaments were present. Her facial appearance had been modified by several plastic surgery procedures. Eczema resolved with age, with occasional flareups. Asthma, headaches, and seizures were additional medical findings. Speech delays, an unusually soft, high-pitched voice, submucous cleft palate, and velopharyngeal insufficiency were noted in childhood. Mild mental retardation was present. At age 30 years she is living independently in her own apartment and working full-time in a nearby sheltered workshop.
Assuntos
Anormalidades Múltiplas/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Deficiências do Desenvolvimento/fisiopatologia , Eczema/fisiopatologia , Face/anormalidades , Feminino , Seguimentos , Humanos , Recém-Nascido , Deficiência Intelectual/fisiopatologia , SíndromeRESUMO
An etiological survey is presented of all suveryl retarded children living in Hertfordshire, at home and in residential care, born between January 1, 1965, and December 31, 1967. One hundred and forty-six children (87 boys and 59 girls) were ascertained, out of a total population of 46,960, with a prevalence of 1 in 320 or 3.1 per 1,000. Approximately 1/3 (47) had the Down syndrome, 1 per 1,000 population. It was possible to establish a diagnosis in a further 45 cases, which included 1 additional case of autosomal chromosome abnormality and 7 each of autosomal dominant, recessive and X-linked conditions; 17 were associated with presumed multifactorial etiological factors; in 6 the condition was thought to have been caused by an environmental agent. It was not possible to establish a cause in the remaining 54 cases. Recurrence risks of severe mental retardation in cases where it is possible to establish a definite diagnosis are discussed and the potential value, for genetic counseling purposes, of a categorizing such patients into broad symptomatological groups, is suggested.
Assuntos
Deficiência Intelectual/etiologia , Dermatoglifia , Síndrome de Down/complicações , Inglaterra , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Masculino , LinhagemRESUMO
Juvenile polyps are the most frequent gastrointestinal polyps with a malignant potential for which the genetic basis is unknown. Juvenile polyps, with a normal epithelium but hypertrophic lamina propria, are histologically quite distinct from adenomatous polyps which have dysplastic changes in epithelial nuclei. Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated somatically in adenomatous polyps and mutated in the germline of patients with familial adenomatous polyposis, is not linked to hereditary juvenile polyposis. We provide the first report indicating that a tumor suppressor gene associated with juvenile polyposis may be located at 10q22.3q24.1. Cytogenetic studies of a patient with juvenile polyposis and multiple congenital abnormalities of the head, extremities, and abdomen revealed a de novo interstitial deletion of Chr 10 as the only defect, del(10)(10q22.3q24.1).
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 10/genética , Pólipos Intestinais/genética , Abdome/anormalidades , Anormalidades Múltiplas/genética , Adulto , Endoscopia Gastrointestinal , Genes Supressores de Tumor/genética , Cabeça/anormalidades , Histocitoquímica , Humanos , Lactente , Pólipos Intestinais/patologia , Cariotipagem , Deformidades Congênitas dos MembrosRESUMO
We describe two additional instances of atelosteogenesis, type III, in a woman and her son. Clinical and radiographic information concerning these individuals allows further definition of this rare skeletal dysplasia. This is the first documentation of survival to adulthood of an individual with this disorder, of prenatal diagnostic assessment of an affected individual, and of vertical transmission suggestive of autosomal dominant inheritance. The clinical and radiologic phenotype of atelosteogenesis, type III overlaps with that of another skeletal dysplasia, autosomal dominant Larsen syndrome; these most likely represent allelic conditions.
Assuntos
Osso e Ossos/anormalidades , Genes Dominantes , Diagnóstico Pré-Natal , Adulto , Osso e Ossos/diagnóstico por imagem , Pré-Escolar , Diagnóstico Diferencial , Nanismo , Feminino , Humanos , Masculino , Radiografia , Sobreviventes , Síndrome , Traqueia/anormalidadesRESUMO
We report a previously apparently undescribed, X-linked recessive basal ganglia disorder segregating in three generations of one family. The affected patients were variably mentally retarded, although some showed strengths in oral reading and memory. Most affected males had frontal bossing and increased head circumference with large calvaria in relation to facial bones. Their height and weight did not differ from that of other relatives; testicular size was average, chromosomes were normal, and results of laboratory investigations for known metabolic disorders were normal. All patients examined had neurological impairment, including persistent frontal lobe reflexes, cogwheel rigidity, postural changes, and Parkinsonian-type tremors. Some had strabismus; several had seizures. Although carriers of the condition were not consistently abnormal, two had suggestive signs. No definitive indication of the disorder was documented in infancy in any affected male, and it is possible that this could be due to lack of careful prospective clinical evaluation rather than to the absence of symptoms in early life.
Assuntos
Doenças dos Gânglios da Base/genética , Deficiência Intelectual/genética , Cromossomo X , Feminino , Ligação Genética , Cabeça/anormalidades , Humanos , Masculino , Doença de Parkinson/genética , Linhagem , Convulsões/genéticaRESUMO
A 9-month-old boy presented with rapid deterioration of psychomotor development. He developed seizures at 2 months, and shortly thereafter lost motor skills and developed feeding difficulties, increased startle response, red maculas, and decreased vision. His measurements, including head circumference, were greater than the 95th centile. No organomegaly was found. Serum determination of the hemoxsaminidases confirmed the diagnosis of Sandhoff disease.
Assuntos
Doença de Sandhoff/diagnóstico , Encéfalo/patologia , Criança , Humanos , Lactente , Transtornos Psicomotores/genética , Transtornos Psicomotores/patologia , Transtornos Psicomotores/fisiopatologia , Doença de Sandhoff/genética , Doença de Sandhoff/patologia , Doença de Sandhoff/fisiopatologiaRESUMO
We describe severe neonatal Kniest dysplasia. Radiological findings in a severe case include short bowed tubular bones with exaggerated metaphyseal flare, moderate platyspondyly with vertical clefts of the vertebral bodies, and characteristically shaped iliac bones. Pathologic findings included a disorganized physeal growth plate, soft crumbly cartilage with a "Swiss-cheese" appearance, and diastase resistant intracytoplasmic inclusions in the resting chondrocytes. Transmission electronmicroscopy showed dilated cisternae of rough endoplasmic reticulum with finely granular material of accumulated protein. Scanning electronmicroscopy documented striking fragmentation and disintegration of collagen fibrils resulting in a web-like pattern and large open cyst-like spaces, and deficiency and disorganization of the collagen fibrils.
Assuntos
Cartilagem/patologia , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/patologia , Adulto , Cartilagem/ultraestrutura , Retículo Endoplasmático Rugoso/patologia , Retículo Endoplasmático Rugoso/ultraestrutura , Evolução Fatal , Feminino , Lâmina de Crescimento/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Microscopia Eletrônica de Varredura , RadiografiaRESUMO
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.
Assuntos
Edema/genética , Doenças Fetais/genética , Poli-Hidrâmnios/diagnóstico , Complicações na Gravidez/diagnóstico , Diagnóstico Diferencial , Edema/diagnóstico , Feminino , Doenças Fetais/diagnóstico , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-NatalRESUMO
This study provides statistically appropriate head circumference reference curves for males and females with Down syndrome (DS) from birth to 36 months of age. A total of 239 males and 182 females from five study populations, yielding a combination of cross-sectional and longitudinal data, were used for the analysis. The method of least squares was used to test the fit of the growth model y = a+bx+c[log(x + 1)], where x is age in months. These standardized curves should provide information of value in the medical, physical, and developmental management of children with DS.
Assuntos
Síndrome de Down/patologia , Cabeça/patologia , Biometria , Cefalometria , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valores de ReferênciaRESUMO
Walker-Warburg syndrome (WWS) is an autosomal recessive disorder manifest by characteristic brain and eye malformations. We reviewed data on 21 of our patients and an additional 42 patients from the literature. From this review, we expand the phenotype to include congenital muscular dystrophy (CMD) and cleft lip and/or palate (CLP), and revise the diagnostic criteria. Four abnormalities were present in all patients checked for these anomalies: type II lissencephaly (21/21), cerebellar malformation (20/20), retinal malformation (18/18), and CMD (14/14). We propose that these comprise necessary and sufficient diagnostic criteria for WWS. Two other frequently observed abnormalities, ventricular dilatation with or without hydrocephalus (20/21) and anterior chamber malformation (16/21), are helpful but not necessary diagnostic criteria because they were not constant. All other abnormalities occurred less frequently. Congenital macrocephaly with hydrocephalus (11/19) was more common than congenital microcephaly (3/19). Dandy-Walker malformation (10/19) was sometimes associated with posterior cephalocele (5/21). Additional abnormalities included slit-like ventricles (1/21), microphthalmia (8/21), ocular colobomas (3/15), congenital cataracts (7/20), genital anomalies in males (5/8), and CLP (4/21). Median survival in our series was 9 months. A related autosomal recessive disorder, Fukuyama congenital muscular dystrophy, consists of similar but less severe brain changes and CMD. It differs from WWS because of consistently less frequent and severe cerebellar and retinal abnormalities. We think that WWS is identical to "cerebro-oculo-muscular syndrome" and "muscle, eye, and brain disease."
Assuntos
Encéfalo/anormalidades , Aberrações Cromossômicas/genética , Anormalidades do Olho , Genes Recessivos , Distrofias Musculares/genética , Cerebelo/anormalidades , Ventrículos Cerebrais/anormalidades , Transtornos Cromossômicos , Fenda Labial/genética , Fissura Palatina/genética , Encefalocele/genética , Feminino , Humanos , Hidrocefalia/genética , Lactente , Masculino , SíndromeRESUMO
Ovarian germ cell cancers are rare malignancies accounting for less than 5% of all ovarian cancers. We present a family in which three closely related women were diagnosed with ovarian germ cell malignancies. This family's cancer history prompted a family history investigation of women treated for ovarian germ cell malignancies in the Gynecologic-Oncology Clinic at the University of Wisconsin. One of the eight patients whose family histories were reviewed had an uncle who had been diagnosed with testicular germ cell cancer. A review found six other previously reported families in which more than one relative had been diagnosed with a malignant ovarian germ cell tumor. Additionally, several cases of families with both males and females diagnosed with germ cell cancers have been documented. The low incidence of ovarian germ cell cancers suggests that multiple occurrences in the same family may not be due to chance. Rather, it is possible that a gene conferring susceptibility to ovarian germ cell cancers, and possibly to germ cell tumors in males as well, is present in at least some of these families.
Assuntos
Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Ovarianas/genética , Adolescente , Adulto , Suscetibilidade a Doenças , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Ovarianas/epidemiologia , Linhagem , Neoplasias Testiculares/genética , WisconsinRESUMO
We report on four patients with tricho-rhino-phalangeal syndrome with exostoses (TRPSE) who were not mentally retarded and review 32 previously published cases. These data enable more complete delineation of the phenotype and document the variability of the clinical and radiographic manifestations. Information on the genetics and the association with del(8q) is discussed, as are management and avenues for further investigation. The apparent variability of intelligence in TRPSE patients together with the high incidence of other problems, including significant delay in speech development and hearing loss, make systematic multidisciplinary evaluation and long-term treatment necessary to achieve the best outcome.
Assuntos
Anormalidades Múltiplas/diagnóstico , Exostose/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Deleção Cromossômica , Exostose/complicações , Feminino , Humanos , Técnicas In Vitro , Deficiência Intelectual/complicações , Fenótipo , SíndromeRESUMO
We evaluated the pregnancies of 427 women who conceived through artificial insemination by donor (AID) at our clinic over a 12-year period. Initial phone contact was followed by a questionnaire. Outcome was known for 594 of the 606 pregnancies, with a total of 502 live-born children including 15 sets of twins. The spontaneous abortion rate was 16.5%, with no difference between fresh- and frozen-semen pregnancies. Significant correlations were found between spontaneous abortion rate and maternal age (P less than .001) and spontaneous abortion rate and cycle of conception (P less than .025). Follow-up was completed on 481 children, among whom the following were found: one chromosomal anomaly, 22 major congenital anomalies, four children with possibly syndromic conditions, and 38 with minor congenital anomalies. Of the school-aged children, 5.8% had recognized learning disabilities and 10.5% were considered gifted by their schools. We also investigated the psychological impact of AID on each family. The majority of couples (71.7%) informed their obstetricians of the AID. Half of the couples did not tell any family or friends. Many couples did not (47%) or probably did not (14%) plan to tell their children of their origins. The divorce rate among those with AID children was 7.2%, which was significantly less (P less than .01) than that in a matched population. Psychological counseling specifically related to AID was sought by 2.8% of the couples. We conclude that AID children are at similar risk for congenital anomalies as normally conceived children, but they experience lower rates of family dissolution.
Assuntos
Adaptação Psicológica , Família/psicologia , Inseminação Artificial Heteróloga , Inseminação Artificial , Resultado da Gravidez , Aborto Espontâneo/epidemiologia , Adolescente , Atitude , Criança , Pré-Escolar , Anormalidades Congênitas/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Infertilidade Masculina/etiologia , Inseminação Artificial/psicologia , Inseminação Artificial Heteróloga/psicologia , Masculino , Casamento , GravidezRESUMO
We report three siblings (two boys and girl) with familial (autosomal recessive) infantile olivopontocerebellar atrophy (OPCA) associated with lower motoneuron involvement. Brain autopsy findings in two of the children revealed a multisystem degeneration characterized by marked hypoplasia of phylogenetically new parts of the brain stem (basis pontis and inferior olivary nuclei) associated with hypoplasia of the neocerebellum, both cerebellar and cerebral peduncle. All three infants died before six months of age. The clinical features are characterized by severe hypotonia, areflexia, failure to thrive, respiratory insufficiency in all cases, cardiomyopathy and dislocated hips at birth in two of the three siblings. Extensive serum, urinary and leukocyte enzyme assays in the second infant failed to disclose a specific metabolic abnormality. The diagnosis of OPCA was established prior to death by Magnetic Resonance Imaging (MRI) in the youngest infant. Since OPCA represents a heterogeneous group of diseases, correlation of neuropathologic, clinical, genetic and MRI findings at early stages of evolution becomes crucial in the understanding of the nosology of OPCA and its variants.
Assuntos
Atrofia Muscular Espinal , Atrofias Olivopontocerebelares , Atrofias Musculares Espinais da Infância , Degenerações Espinocerebelares , Feminino , Genes Recessivos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Microscopia Eletrônica , Atrofia Muscular Espinal/complicações , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patologia , Atrofias Olivopontocerebelares/complicações , Atrofias Olivopontocerebelares/genética , Atrofias Olivopontocerebelares/patologia , Linhagem , Atrofias Musculares Espinais da Infância/complicações , Atrofias Musculares Espinais da Infância/genética , Atrofias Musculares Espinais da Infância/patologia , Degenerações Espinocerebelares/complicações , Degenerações Espinocerebelares/genética , Degenerações Espinocerebelares/patologiaRESUMO
Using the formaldehyde-induced fluorescence method, we found a peculiar rosary-type swelling of the adrenergic axons in the peripheral nerves, deficiency of the perivascular adrenergic plexuses in the visceral and cerebral arteries, and reduction of noradrenergic fluorescence in the tegmental and hypothalamic regions of a 3-year-old boy who had typical Menkes' syndrome (kinky hair syndrome). The nigrostriated neurons retained moderate intensity of fluorescence compared with those in postmortem (control) brains. Histologically, marked dilatation of the visceral, meningeal and cerebral arteries were noted. Copper deficiency, the cause of this disease, induces failure of central and peripheral noradrenergic neurons and leads to abnormal vasodilatation.