RESUMO
OBJECTIVE: To report the phenotypic spectrum and management issues of children with Kabuki syndrome (Niikawa-Kuroki syndrome) from North America. DESIGN: A case series of children (n = 18) with clinical findings of Kabuki syndrome. SETTING: Medical genetics clinics in Washington, Alaska, and Arizona. RESULTS: Most patients had postnatal growth retardation, and all had developmental delay and hypotonia. Feeding difficulties, with or without cleft palate, were common; 5 patients required gastrostomy tube placement. Developmental quotients/IQs in all but 2 were 60 or less. Seizures were seen in less than half of the patients, but ophthalmologic and otologic problems were common, particularly recurrent otitis media. Congenital heart defects were present in 7 (39%); 3 patients underwent repair of coarctation of the aorta. Other features included urinary tract anomalies, malabsorption, joint hypermobility and dislocation, congenital hypothyroidism, idiopathic thrombocytopenic purpura, and in one patient, autoimmune hemolytic anemia and hypogammaglobulinemia. All patients had negative family histories for Kabuki syndrome. CONCLUSIONS: Kabuki syndrome is a mental retardation-malformation syndrome affecting multiple organ systems, with a broad spectrum of neuromuscular dysfunction and mental ability. Given that 18 ethnically diverse patients were identified from 2 genetics programs, it appears that this syndrome is more common in North American non-Japanese patients than previously appreciated.
Assuntos
Anormalidades Múltiplas/genética , Deficiências do Desenvolvimento/genética , Face/anormalidades , Deficiência Intelectual/genética , Anormalidades Múltiplas/classificação , Anormalidades Múltiplas/fisiopatologia , Anormalidades Múltiplas/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Deficiências do Desenvolvimento/classificação , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/terapia , Feminino , Gastrostomia , Humanos , Lactente , Deficiência Intelectual/classificação , Masculino , Hipotonia Muscular/genética , Fenótipo , Síndrome , Estados UnidosRESUMO
OBJECTIVE: Although hypopigmented macules are an important manifestation of tuberous sclerosis (TS), the probability of TS in healthy individuals who have hypopigmented macules is unknown. The purpose of this study was to establish the prevalence of hypopigmented macules among a cross section of the general white population. STUDY DESIGN: The skin of 423 white individuals younger than 45 years of age was screened for hypopigmented macules with ambient incandescent and fluorescent light and a Wood lamp. Indirect ophthalmoscopy was performed in patients with unexplained hypopigmentation to screen for retinal manifestations of TS. RESULTS: Twenty individuals (4.7%) had at least one hypopigmented macule. Of these, four had more than one macule. None had more than three. Two (8%) of the 25 hypopigmented macules were identified only with a Wood lamp. Indirect ophthalmoscopy was performed in 13 (65%) of these 20 individuals. None showed the retinal findings of TS. CONCLUSIONS: The prevalence of hypopigmented macules in the general population has been underestimated. The presence of a few hypopigmented macules on the skin of an otherwise healthy individual without a family history of TS need not prompt an evaluation to rule out this disorder.
Assuntos
Hipopigmentação/epidemiologia , Esclerose Tuberosa/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hipopigmentação/complicações , Hipopigmentação/patologia , Lactente , Masculino , Prevalência , Esclerose Tuberosa/complicaçõesRESUMO
Geleophysic dysplasia is characterized by typical facies ("happy natured"), small hands and feet, short stature, hepatomegaly, and progressive cardiac disease. We describe five patients (two of whom are siblings) with this disorder and document its variable expressivity. The facies were strikingly similar with small nose, anteverted nostrils, broad nasal bridge, and long thin upper lip with flat and long philtrum. Behavior, development, and intelligence were normal. Growth delay was noticed during infancy, and the two patients who completed normal puberty had marked short stature (140 and 150 cm), with relatively lean body habitus. The hands and feet were small, with short, plump tubular bones and broad proximal phalanges, associated with marked limitation in motion of fingers and wrists. The liver was enlarged after the age of 3 years. Two patients had mild mitral and tricuspid valve stenosis and one had severe aortic stenosis. The most severely affected child died at 3 1/2 years of age of airway obstruction as a result of progressive tracheal narrowing. Lysosomal storage vacuoles were found in skin epithelial cells from three patients whose skin was examined, and in the tracheal mucosa, liver, cartilage and macrophages of the child who died. The basic defect of this autosomal recessive lysosomal storage disease remains to be determined.
Assuntos
Expressão Facial , Transtornos do Crescimento/genética , Doenças das Valvas Cardíacas/genética , Hepatomegalia/genética , Erros Inatos do Metabolismo/genética , Adolescente , Criança , Pré-Escolar , Contratura/genética , Feminino , Genes Recessivos , Humanos , Masculino , Desempenho Psicomotor , Estenose Traqueal/genéticaRESUMO
Thirteen patients with hypopigmentation of the skin characteristic of hypomelanosis of Ito, and with developmental disabilities or structural malformations, or both, were examined at our center. Eight were found to have abnormal karyotypes in lymphocytes, fibroblasts, or both. No single clinical feature was predictive of chromosome imbalance in this group of patients. Cytogenetic findings included a balanced de novo X-autosome translocation; ring 10; 45,X/46,X,+ring; mosaic del 13q11 (fibroblasts); mosaic triploidy (fibroblasts); mosaic tetrasomy 12p (fibroblasts); mosaic apparently balanced 15;22 translocation (peripheral blood); and mosaic trisomy 18 (peripheral blood). Hypomelanosis of Ito is characterized by swirly hypopigmentation or depigmentation of the skin with or without other malformations. Autosomal dominant, autosomal recessive, and X-linked dominant inheritance have been suggested but not confirmed. Chromosomal aneuploidy has also been reported. We believe that hypomelanosis of Ito is an etiologically heterogeneous physical finding, and recommend karyotyping of multiple tissues of all patients with abnormal cutaneous pigmentation associated with developmental delay or structural malformations.
Assuntos
Aberrações Cromossômicas/genética , Mosaicismo/genética , Transtornos da Pigmentação/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Cariotipagem , Masculino , Transtornos da Pigmentação/patologia , Síndrome , Translocação Genética , Cromossomo XRESUMO
We report three boys with severe hypospadias and bilaterally palpable testes with abnormalities of the Y chromosome detected by Q-banding. Severe hypospadias with palpable testes is an unusual presentation for Y chromosome abnormalities. Based on our experience, we recommend that boys with this phenotype undergo complete cytogenetic evaluation, because Y chromosome abnormalities prompt additional management concerns.
Assuntos
Hipospadia/genética , Aberrações dos Cromossomos Sexuais , Cromossomo Y , Humanos , Recém-Nascido , Masculino , FenótipoRESUMO
Russell-Silver syndrome was reevaluated 2.9 to 13.0 years after initial diagnosis in 15 patients. At follow-up, five of the 15 patients exhibited late catch-up growth and had normal height, six had developmental delays or mental retardation, and asymmetry was present in five. Given the great variability in the long-term prognosis for growth and development in patients with Russell-Silver syndrome, there is a need to reevaluate this syndrome and its clinical implications.
Assuntos
Deficiências do Desenvolvimento/diagnóstico , Transtornos do Crescimento/diagnóstico , Adolescente , Estatura , Criança , Pré-Escolar , Deficiências do Desenvolvimento/fisiopatologia , Expressão Facial , Feminino , Retardo do Crescimento Fetal/diagnóstico , Seguimentos , Transtornos do Crescimento/fisiopatologia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Deficiência Intelectual/diagnóstico , Masculino , Gravidez , Prognóstico , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/fisiopatologia , Maturidade Sexual , Síndrome , Fatores de TempoAssuntos
Anormalidades Múltiplas/complicações , Anus Imperfurado/complicações , Transtornos do Desenvolvimento Sexual/complicações , Sistema Urinário/anormalidades , Transtornos do Desenvolvimento Sexual/genética , Feminino , Humanos , Recém-Nascido , Cariotipagem , Ductos Paramesonéfricos/patologiaRESUMO
We report two families in which müllerian anomalies or renal agenesis appeared to be caused by an autosomal dominant gene that produces unilateral or bilateral renal agenesis and a spectrum of müllerian anomalies. This single gene disorder may account for the high incidence of müllerian anomalies observed in females with bilateral renal agenesis and the increased frequency of renal anomalies in patients with müllerian malformations. The range of müllerian anomalies in this disorder includes bicornuate uterus, uterus didelphys, Rokitansky- Kuster -Hauser syndrome (vaginal atresia with or without absence of the uterus), and total müllerian aplasia. Gene expression is not sex limited. Affected males can have bilateral or unilateral renal agenesis, and possibly may have unilateral or bilateral absence of the vas deferens or seminal vesicles. We suggest that autosomal dominant urogenital adysplasia is common, but underdiagnosed because of the deceptive variability in gene expression. In addition, reduced gene penetrance and reduced biologic fitness from lethal renal anomalies or genital tract anomalies may obscure the autosomal dominant nature of this disorder in most families.
Assuntos
Rim/anormalidades , Ductos Paramesonéfricos/patologia , Adulto , Criança , Feminino , Genes Dominantes , Humanos , Masculino , LinhagemRESUMO
Two siblings are reported who appear to have an autosomal recessive disorder of eye and central nervous system anomalies. The findings in fourteen previously described and similarly affected patients are summarized. Ocular anomalies include microphthalmos, megalocornea, the Peter anomaly, cataract, coloboma, persistent hyperplastic primary vitreous, and retinal detachment with retinal dysplasia. Central nervous system malformations include agyria-pachygyria, cerebellar dysplasia, encephalocele, Dandy-Walker cyst, and hydrocephalus. We suggest that this disorder be known as Warburg syndrome.
Assuntos
Encéfalo/anormalidades , Aberrações Cromossômicas/genética , Anormalidades do Olho , Encefalopatias/etiologia , Encefalopatias/genética , Transtornos Cromossômicos , Oftalmopatias/etiologia , Oftalmopatias/genética , Feminino , Humanos , Recém-Nascido , Masculino , Síndrome , Terminologia como AssuntoRESUMO
We report 21 patients with choanal atresia or ocular coloboma or both who have certain other associated anomalies, including congenital heart disease, postnatal growth deficiency, mental retardation and/or CNS anomalies, microphallus and cryptorchidism, and ear anomalies and/or deafness. Facial palsy, micrognathia, cleft palate, and swallowing difficulties were also common. It has not been possible to define a single etiology or a syndrome in these patients. We propose the mnemonic CHARGE (C-coloboma, H-heart disease, A-atresia choanae, R-retarded growth and retarded development and/or CNS anomalies, G-genital hypoplasia, and E-ear anomalies and/or deafness) to describe the features of this association.
Assuntos
Anormalidades Múltiplas , Coloboma/complicações , Cardiopatias Congênitas/complicações , Nasofaringe/anormalidades , Nariz/anormalidades , Adulto , Sistema Nervoso Central/anormalidades , Surdez/complicações , Deficiências do Desenvolvimento/complicações , Orelha/anormalidades , Anormalidades do Olho , Feminino , Transtornos do Crescimento/complicações , Humanos , Masculino , Disfunções Sexuais Fisiológicas/complicaçõesRESUMO
Abdominal muscle deficiency with a "prune belly" abdomen as been a major feature of the so-called prune belly syndrome, which has been regarded as a specific entity, although the etiology and developmental pathology are not understood. We present evidence that abdominal muscle deficiency is an etiologically nonspecific anatomic defect which is secondary to fetal abdominal distention of various causes. One of the more common causes is urethral obstruction with consequent early bladder distention, causing abdominal distention and other anomalies, a constellation of findings which we have termed the urethral obstruction malformation complex. This interpretation of the etiology of most cases of prune belly syndrome accounts for the male predominance, the observed variability in severity, and the lack of a defined mode of inheritance. Recurrence risk figures need to be redefined for each specific obstructing lesion of the urethra. The possibility of early prenatal diagnosis and management of fetuses with urethral obstruction needs further study.