RESUMO
Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare hamartomatous polyposis condition with features of macrocephaly, intestinal juvenile polyposis, developmental delay, lipomas, and pigmentation spots of the male genitalia. An autosomal dominant pattern of inheritance exists in some families, but others appear as sporadic cases. Germ-line mutations in PTEN, a tyrosine phosphatase and putative tumor suppressor gene, have been demonstrated in two families with BRRS, and chromatin loss at the PTEN gene locus on chromosome 10q23 has been demonstrated in two BRRS patients. Germ-line mutations in PTEN have also been described in Cowden disease and in a small number of patients with juvenile polyposis syndrome. In an attempt to assess the nature of PTEN mutations in BRRS, we analyzed three sporadic BRRS patients for chromosome 10q23 deletion or PTEN germ-line mutations. All 3 patients demonstrated no loss of parental alleles at 15 chromosome 10q23 markers that encompassed the region of PTEN. In addition, analysis of mRNA and genomic DNA revealed no nonsense, missense, or insertion/deletion mutations of PTEN. Thus, other mechanisms besides mutation of PTEN must have occurred to cause BRRS in these patients. We speculate that BRRS and juvenile polyposis syndrome may have a heterogeneous etiology to cause their syndromes.
Assuntos
Mutação em Linhagem Germinativa/genética , Síndrome do Hamartoma Múltiplo/genética , Pólipos Intestinais/genética , Monoéster Fosfórico Hidrolases , Transtornos da Pigmentação/genética , Proteínas Tirosina Fosfatases/genética , Proteínas Supressoras de Tumor , DNA/genética , Deficiências do Desenvolvimento/genética , Humanos , Masculino , PTEN Fosfo-Hidrolase , RNA Mensageiro/genética , SíndromeRESUMO
We retrospectively reviewed 19 patients (11 male, 8 female) with infantile systemic hyalinosis (ISH) seen at a tertiary care hospital. Fifteen patients (83.3%) presented in the neonatal period. The referral diagnosis was inaccurate in 14 patients (73.7%). Thirteen patients were products of first-degree cousin marriages (68%) and 5 families had more than one affected child. All patients had painful joint contractures and typical mucocutaneous changes (hyper-pigmented sclerodermatous skin over the knuckles and malleoli, gingival hyperplasia, subcutaneous and perianal fleshy nodules). Growth failure was noted in all of them and 39% had profuse diarrhea, 72% had low serum albumin. Radiological findings included osteopenia, periosteal reaction and osteolytic lesions. Tissue biopsy was consistent with the diagnosis in the 8 patients who had the biopsies. Despite aggressive management with physiotherapy and different medications (including NSAIDs, penicillamine and methotrexate), the disorder was progressive and none of them showed improvement. 16 patients died with a mean age of 11 months and only 3 are alive with a mean age of 20 months. This report represents the largest series of ISH. Our data suggests that ISH is a commonly diagnosed disorder in Saudi Arabia and among Arabs.
Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Fácies , Doenças do Recém-Nascido/diagnóstico , Árabes , Doenças do Tecido Conjuntivo/etnologia , Doenças do Tecido Conjuntivo/mortalidade , Consanguinidade , Contratura/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/etnologia , Doenças do Recém-Nascido/mortalidade , Artropatias/etiologia , Masculino , Mucosa , Estudos Retrospectivos , Arábia Saudita/etnologia , Dermatopatias/etiologia , SíndromeAssuntos
Artérias/anormalidades , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Proteínas Facilitadoras de Transporte de Glucose/genética , Hérnias Diafragmáticas Congênitas , Mutação , Doenças Cardiovasculares/congênito , Hérnia Diafragmática/complicações , Humanos , SíndromeRESUMO
Two brothers of normal first-cousin parents were found to have Robinow syndrome. Their paternal uncle also married a first cousin and had 3 similarly affected children (2 boys, 1 girl). The 2 affected brothers had short stature, mesomelic and acromelic brachymelia, characteristic face with hypertelorism, wide palpebral fissures, midface hypoplasia and large mouth, and hypogenitalism. Parental consanguinity and affected individuals in 2 sibships of common ancestry strongly suggest autosomal recessive inheritance. Similar cases from the literature are briefly reviewed.
Assuntos
Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/genética , Expressão Facial , Genes Recessivos , Genitália Masculina/anormalidades , Transtornos do Crescimento/genética , Hipertelorismo/genética , Criança , Consanguinidade , Humanos , Lactente , Masculino , Linhagem , SíndromeRESUMO
Craniofrontonasal dysplasia, a distinct malformation syndrome, is characterized by varying degrees of frontonasal dysplasia, craniosynostosis, and variable extracranial abnormalities--in particular, brittle nails with prominent longitudinal grooves or splitting. There is marked female preponderance and variable expressivity not only between males and females but also between females. However, mode of inheritance is still unclear. We describe a large Arab kindred with 16 individuals (9 males, 7 females) in 4 generations having an apparently new autosomal dominant syndrome with features of craniofrontonasal dysplasia but with normal or slightly broad nasal tip and without evidence of craniosynostosis or nail abnormalities. These cases were segregating in 5 sibships and include male to male transmission with full expression in males and females. Chromosomes of the proposita and her father were normal. Aarskog syndrome has been also considered in the differential diagnosis and was excluded.
Assuntos
Anormalidades Múltiplas/genética , Seio Frontal/anormalidades , Nariz/anormalidades , Crânio/anormalidades , Adulto , Criança , Pré-Escolar , Feminino , Genes Dominantes , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , SíndromeRESUMO
We report on a 6-year-old girl with Costello syndrome. Main manifestations included poor postnatal growth, relative macrocephaly, curly hair, distinct "coarse" face, mild mental retardation, happy and sociable personality, loose dark skin particularly of hands and feet, acanthosis nigricans, thin deep set nails, enamel hypoplasia of teeth, and hyperextensible joints. The absence to date of perioral and nasal papillomata in this girl suggests that Costello syndrome is clinically recognizable even before appearance of such papillomata. Manifestations are compared to the four previously reported sporadic cases.
Assuntos
Anormalidades Múltiplas , Nanismo , Face/anormalidades , Deficiência Intelectual , Anormalidades da Pele , Criança , Hipoplasia do Esmalte Dentário , Feminino , Deformidades Congênitas do Pé , Cabelo/anormalidades , Sopros Cardíacos , Humanos , Instabilidade Articular , Fisiognomia , SíndromeRESUMO
We report on 3 brothers with hypertelorism, hypospadias, and tetralogy of Fallot. Parents are first cousins once removed; the father has apparent hypertelorism. An apparently normal paternal uncle who is married to a second cousin also has a daughter with hypertelorism and tetralogy of Fallot. All similarly affected relatives have mild or borderline mental retardation. The combination of anomalies may represent a previously undescribed autosomal recessive disorder.
Assuntos
Doenças do Desenvolvimento Ósseo/diagnóstico , Hipertelorismo/diagnóstico , Hipospadia/diagnóstico , Tetralogia de Fallot/diagnóstico , Criança , Pré-Escolar , Consanguinidade , Feminino , Humanos , Lactente , Masculino , SíndromeRESUMO
The urofacial syndrome is an autosomal recessive disorder of distorted facial expression and neurogenic bladder with resultant urogenital tract damage. We report on an 8-year-old boy of consanguineous Arab parents with inverted facial expression upon laughing and renal changes as a consequence of a neurogenic bladder in addition to hydrocephalus due to stenosis of the aqueduct of Sylvius. We suggest that the association is not fortuitous and probably widens the spectrum of urofacial syndrome or represents a distinct entity mimicking the urofacial syndrome.
Assuntos
Aqueduto do Mesencéfalo/patologia , Expressão Facial , Hidrocefalia/etiologia , Bexiga Urinaria Neurogênica , Criança , Consanguinidade , Constrição Patológica , Genes Recessivos/genética , Humanos , Rim/patologia , Masculino , Síndrome , Tomografia Computadorizada por Raios XRESUMO
We report on 3 sibs (2 boys and a girl) with a previously apparently unrecognized combination of anonychia congenita and microcephaly with normal intelligence. The shape of the head is normal. Other anomalies include clinodactyly of the fifth fingers and bilateral single transverse palmar creases. Skeletal survey was normal in the 2 older children. These children and their first-cousin Iranian parents have widely spaced teeth. The children's first cousin also has total anonychia congenita and apparently small head. We review anonychia congenita, and conclude that the presently reported family with a "new autosomal-recessive disorder" provides further evidence of the heterogeneity of this condition.
Assuntos
Anormalidades Múltiplas/psicologia , Inteligência , Microcefalia/psicologia , Unhas Malformadas , Anormalidades Múltiplas/genética , Criança , Pré-Escolar , Consanguinidade , Feminino , Genes Recessivos , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/psicologia , Humanos , Masculino , Microcefalia/genética , Pessoa de Meia-Idade , Linhagem , SíndromeRESUMO
In 1970, Sandrow et al. (J Bone Joint Surg 52-A:363-370) described a syndrome of ulnar and fibular dimelia with facial abnormalities present in 2 generations in a family. We describe a new patient with similar manifestations, establishing this constellation of anomalies as a distinct syndrome.
Assuntos
Anormalidades Múltiplas/patologia , Face/anormalidades , Deformidades Congênitas do Pé/patologia , Deformidades Congênitas da Mão/patologia , Anormalidades Múltiplas/embriologia , Anormalidades Múltiplas/genética , Deformidades Congênitas do Pé/embriologia , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/embriologia , Deformidades Congênitas da Mão/genética , Humanos , Lactente , Masculino , Sindactilia/embriologia , Sindactilia/genética , Sindactilia/patologia , SíndromeRESUMO
We describe a combination of multiple congenital anomalies, severe psychomotor retardation and symmetrical circumferential skin creases of arms and legs in a 4.5-year-old male. Craniofacial anomalies included: a high forehead, elongated face, bitemporal sparseness of hair, broad eyebrows, blepharophimosis, bilateral microphthalmia and microcornea, severe optic nerve hypoplasia, epicanthic folds, telecanthus, broad nasal bridge, puffy cheeks, microstomia, cleft palate, enamel hypoplasia, micrognathia, microtia with stenotic ear canals and posteriorly angulated ears. Head circumference was on the 10th centile and a CT scan showed dilated lateral ventricles. Intracranial pressure was not increased. Other abnormalities included: short stature, loose skin, hypotonia, pectus excavatum, inguinal and umbilical hernias, severe scoliosis, hypoplastic scrotum, long fingers and overlapping toes. Echocardiography showed tricuspid regurgitation. Chromosomes were apparently normal. Differentiation from "Michelin tire baby syndrome" and amniotic band sequence is discussed.
Assuntos
Anormalidades Múltiplas , Anormalidades da Pele , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Adulto , Braço/anormalidades , Pré-Escolar , Feminino , Humanos , Deficiência Intelectual , Perna (Membro)/anormalidades , Masculino , Pessoa de Meia-Idade , SíndromeRESUMO
Autosomal recessive microcephaly is usually associated with moderate to severe mental retardation. An apparently new autosomal recessive disorder comprising a characteristic facial appearance associated with microcephaly and normal intelligence, immunodeficiency, and increased risk for lymphoreticular malignancies has been described recently. We report on a large Arab kindred with frequent consanguineous marriages and eight cases in five sibships with microcephaly, peculiar facies, and normal intelligence. Of these cases, two died of an acute lymphoreticular malignancy or bronchopneumonia. Immunological and chromosomal studies carried out for the three affected living sibs were normal. The existence of an autosomal recessive nonsyndromal variant of microcephaly with normal intelligence is proposed and discussed.
Assuntos
Microcefalia/genética , Adolescente , Criança , Feminino , Genes Recessivos , Humanos , Inteligência , Masculino , LinhagemRESUMO
Five individuals in one family, including dizygotic male twins, a half brother and their mother, had Aarskog syndrome (AS). Phenotypic variability is wide not only between mother and sons but also between sibs. Collectively, the affected relatives have the full spectrum of findings seen in AS. Based on analysis of this family and others from the literature, we derive primary and secondary diagnostic criteria for AS. Primary criteria include: short stature, hypertelorism, short nose with anteverted nares, maxillary hypoplasia, a crease below the lower lip, mild interdigital webbing with short and broad hands, short fifth finger with clinodactyly, and shawl scrotum. Secondary criteria include: abnormal auricles with fleshy lobules, posteriorly angulated ears, widow's peak, ptosis, downward slant of palpebral fissures, joint hyperextensibility, broad feet with bulbous toes, cryptorchidism, inguinal hernia, and prominent umbilicus. Literature pertaining to the clinical manifestations and genetics of AS is reviewed and nosology of similar syndromes is discussed.
Assuntos
Anormalidades Múltiplas/genética , Face/anormalidades , Genitália Masculina/anormalidades , Anormalidades Múltiplas/classificação , Anormalidades Múltiplas/diagnóstico , Adolescente , Adulto , Pré-Escolar , Doenças em Gêmeos/genética , Feminino , Deformidades Congênitas da Mão/genética , Humanos , Hipertelorismo/genética , Masculino , Linhagem , SíndromeRESUMO
The recurrence of anencephaly in families has been explained on a multifactorial basis. We present two unrelated families with three sibships of several nonsyndromal anencephalics including two pairs of concordantly affected like-sex twins. A rare autosomal recessive variant is proposed and inheritance is discussed in view of parental consanguinity among the two affected sibships in one family.
Assuntos
Anencefalia/genética , Doenças em Gêmeos , Genes Recessivos , Consanguinidade , Feminino , Variação Genética , Humanos , Kuweit , Masculino , Linhagem , RecidivaRESUMO
We report a patient with terminal transverse limb defects associated with persistent primitive aorto-pulmonary vascular connections leading to supra-systemic pulmonary artery pressure. It is likely that this patient represents a vascular disruption sequence or as an alternative a form of Adams-Oliver syndrome. These assumptions are based only on the association of vascular abnormalities as an emerging and apparently important association with transverse limb defects despite the absence of aplasia cutis congenita commonly associated with Adams-Oliver syndrome.
Assuntos
Aorta/anormalidades , Deformidades Congênitas dos Membros/patologia , Artéria Pulmonar/anormalidades , Pré-Escolar , Diagnóstico Diferencial , Humanos , Masculino , Síndrome , Doenças Vasculares/congênitoRESUMO
We report on a patient with a unique constellation of anomalies comprising trigonomicrocephaly, asymmetric severe micrognathia, large ears, atrioventricular septal defect, vertebral anomalies, bilateral cutaneous syndactyly of fingers and toes, unilateral cryptorchidism and multiple café-au-lait spots. The mother of the propositus has multiple café-au-lait spots. Search of POSSUM and the London Dysmorphology Database (LDDB) uncovered no similar case. We think that this patient represents a new acrocraniofacial dysostosis syndrome.
Assuntos
Anormalidades Múltiplas/patologia , Orelha/anormalidades , Microcefalia/patologia , Micrognatismo/patologia , Anormalidades Múltiplas/genética , Acrocefalossindactilia/patologia , Manchas Café com Leite/genética , Manchas Café com Leite/patologia , Disostose Craniofacial/patologia , Saúde da Família , Defeitos dos Septos Cardíacos/patologia , Humanos , Lactente , Deformidades Congênitas dos Membros/patologia , Masculino , Sindactilia/patologia , SíndromeRESUMO
We report on two cases of Poland sequence (defect of the pectoralis major and hand on the same side) with dextrocardia, and review the literature on such patients. In all 16 reported cases, the Poland defect was on the left side, and associated with a rib defect, whereas most cases of Poland sequence involve the right side, and few have a rib defect. The dextrocardia appeared to be a dextroposition, and was not associated with other cardiac defects, whereas isolated dextrocardias (without situs inversus) frequently are. These observations suggest that the dextrocardia associated with Poland sequence is usually secondary to it.
Assuntos
Dextrocardia , Síndrome de Poland , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
Sotos syndrome is a relatively common overgrowth syndrome with characteristic physiognomy. We report on 3 patients with congenital heart defects out of 14 Sotos syndrome patients studied clinically and or by echocardiography. Review showed another 17 patients with variable cardiac defects, mostly closure defects, making an overall incidence of approximately 8%.
Assuntos
Transtornos do Crescimento/patologia , Cardiopatias Congênitas/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/complicações , Cardiopatias Congênitas/complicações , Humanos , Lactente , Masculino , Fisiognomia , SíndromeRESUMO
We report on an Arab boy with Alagille syndrome and a de novo deletion of the short arm of chromosome 20 with a 46,XY, del(20)(p11.2) chromosome constitution. Other reported cases are briefly reviewed.
Assuntos
Síndrome de Alagille/genética , Deleção Cromossômica , Cromossomos Humanos Par 20 , Humanos , Lactente , Masculino , FenótipoRESUMO
An infant girl with manifestations resembling Optiz trigonocephaly (C) syndrome who died at age 6 days was found to have a complex chromosome abnormality with t(13;18)(q22;q23) and a recombinant chromosome 13 involving duplicated segments of 13q. Precise characterization was possible with the application of fluorescence in situ hybridization (FISH) using chromosome specific probes. The patient's phenotype is compared to that of other syndromes involving trigonocephaly.