Noonan syndrome and its related disorders

The diagnosis of Noonan syndrome still rests on its clinical features. There are several syndromes to consider in the diagnosis of Noonan syndrome. These include cardio-facial-cutaneous syndrome, LEOPARD syndrome, neurofibromatosis-Noonan syndrome and Costello syndrome. The facial appearance and part of the clinical features of these syndromes are very similar to Noonan syndrome. Molecular research likely will elucidate whether these syndromes are variations of Noonan syndrome or etiologically different disorders.     

48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome

Sex chromosome tetrasomy and pentasomy conditions occur in 1:18,000-1:100,000 male births. While often compared with 47,XXY/Klinefelter syndrome because of shared features including tall stature and hypergonadotropic hypogonadism, 48,XXYY, 48,XXXY and 49,XXXXY syndromes are associated with additional physical findings, congenital malformations, medical problems and psychological features. While the spectrum of cognitive abilities extends much higher than originally described, developmental delays, cognitive impairments and behavioural disorders are common and require strong treatment plans. Future research should focus on genotype-phenotype relationships and the development of evidence-based treatments. CONCLUSION: The more complex physical, medical and psychological phenotypes of 48,XXYY, 48,XXXY and 49,XXXXY syndromes make distinction from 47,XXY important; however, all of these conditions share features of hypergonadotropic hypogonadism and the need for increased awareness, biomedical research and the development of evidence-based treatments.     

Cardiac problems in genetic syndromes

Congenital heart disease affects around 0.7% of liveborn infants and is the most frequent cause of death from congenital malformations. This review will consider some of the commoner genetic syndromes associated with congenital heart disease, the spectrum of cardiac defects observed in them and the associated features and comorbidities that may impact on the outcomes of cardiac surgery.     

Kabuki make-up syndrome

Kabuki make-up syndrome is a rare disorder characterized by mental retardation, postnatal dwarfism and peculiar facies. This condition is believed to be common in Japan, but has been reported from other parts of the world. The authors report a case of this syndrome in an eight-year-old girl, with the characteristic findings from India.     

Laurence-Moon-Biedl syndrome (?) and Prader-Willi syndrome (?) in a single family

Mental retardation, hypogonadism, obesity, and abnormal blood sugar regulation were common findings in two siblings. In addition, the 17-year-old female patient showed short stature, muscular hypotonia in infancy, and small hands with tapering fingers suggesting Prader-Willi syndrome, and the 12-year-old male patient showed retinitis pigmentosa, normal height, and normal muscular tonicity suggesting Laurence-Moon-Biedl syndrome, though polydactyly was absent. Possible consideration was discussed.     

Acute Febrile Neutrophilic Dermatosis (Sweet's Syndrome) in Myelodysplastic Syndrome

This is the first report of the rare association of acute febrile neutrophilic dermatosis (Sweet's syndrome) and myelodysplastic syndrome (MDS) in a child. The skin lesions showed a dramatic response to colchicine.     

Co-existence of Dubowitz and hyper-IgE syndromes: A case report

A case of a 5-year-old girl is described whose clinical features included postnatal growth retardation, microcephaly and characteristic facial appearance. These are recognized as the main features of the Dubowitz syndrome. Apart from these features, our patient had recurrent infections of the sinopulmonary tract, high serum IgE levels, defective chemotaxis of polymorphonuclear cells and defective antibody response, findings characterizing the hyper-IgE syndrome. The co-existence of these two syndromes is rare and we suggest that this is the first such case in the literature.Conclusion Patients with the Dubowitz syndrome will require long-term follow up because there is a considerable risk for the syndrome to co-exist with primary immunodeficiency or formalignancies to develop.     

Campomelic Syndrome Associated with Potter's Syndrome and Car diosplenic Syndrome

ABSTRACT Campomelic syndrome is a heterogeneous group of disorders characterized by short-limbed dwarfism with congenital bowing or bending of the long bones particularly in the lower limbs and is frequently associated with a variety of non-skeletal manifestations. Two distinct types are (1) long-limbed campomelic dysplasia with bent bones of normal length and width: (2) short-limbed campomelic dysplasia in which the bent bones are short and wide. We reported an autopsy case of this syndrome.
This male baby with gestational age of 32 weeks was born to a mother with placenta previa, showing abdominal distention and short-limbed appearance. Postmortem examination revealed bilaterally enlarged Potter type 1 polycystic kidneys, a pancreatic cyst, and two spleens in the abdominal cavity. Both lungs were hypoplastic and the heart exhibited multiple congenital anomalies such as double outlet right ventricle, pulmonary artery hy-poplasia, mitral atresia, absence of ductus arteriosus, and inferior vena cava draining into the left atrium. Characteristically both femur bones were curved at proximal two-thirds with slightly shortened lengths. Both humeri also showed bending of distal one-third. Other chondro-osseous abnormalities such as small epiglottis, narrow thorax, dolichoce-phaly, and bilateral equinovarus deformity were noted. These findings were compatible with campomelic dysplasia of long-limbed type accompanying unusual sets of non-skeletal manifestations of Potter's syndrome and cardiosplenic syndrome. Key words: campomelic syndrome, Potter's syndrome, cardiosplenic syndrome     

A patient with features of both Bardet-Biedl and Alström syndromes

We describe a 30-year-old patient with acanthosis nigricans, diabetes mellitus with insulin resistance, hypogonadotropic hypogonadism, pigmentary degeneration of the retina and cerebellar, pyramidal and posteri-or columnar involvement. He had normal mental function, normal hearing and no hexadactyly. The patient had symptoms of both Bardet-Biedl and Alström syndromes, but did not manifest all the main features of either syndrome. This suggests either that the Bardet-Biedl, Alström, Laurence-Moon syndromes (including the variant described by Edwards) have a highly variable expression or that our case is a new variant within this group of syndromes.     

Research in mental retardation: toward an etiologic approach

Over the past two decades, mental retardation research converges on three general themes: co-occurring mental retardation and psychopathology; families of offspring with mental retardation; and the developmental approach regarding behavioral sequences and profiles. Intertwined with each theme is a mounting body of research on genetic mental retardation syndromes. We first review recent progress in each of the three domains--psychopathology, families, and development--based on studies of groups with heterogenous or nonspecific mental retardation. We then show how new findings from specific genetic syndromes take this knowledge even further, as well as aid in the search for genetic, physiological, and environmental mechanisms associated with certain behaviors. We end the review by briefly summarizing our reasons for promoting an etiological approach to future mental retardation research, as well as by discussing methodological and other challenges.     

Chromosome 22q11 Deletion in Patients with Truncus Arteriosus

The association between truncus arteriosus and chromosome 22q11 deletion is well recognized, but the frequency of a chromosome 22q11 deletion has not been characterized in a large series of patients with truncus arteriosus, and little is known about cardiovascular morphologic features associated with a chromosome 22q11 deletion in this group of patients. We prospectively enrolled 50 consecutive patients with truncus arteriosus who were admitted to The Childrens Hospital of Philadelphia between November 1991 and December 2001. Patients were studied for chromosome 22q11 deletion using fluorescence in situ hybridization. Correlations between anatomic features and chromosome 22q11 deletion were assessed. A chromosome 22q11 deletion was detected in 20 of the 50 patients (40%). Anatomic features that were significantly associated with a chromosome 22q11 deletion included a right-sided aortic arch, an abnormal aortic arch branching pattern, both abnormal sidedness and branching of the aortic arch, and the combined category of either abnormal sidedness or branching of the aortic arch. There was a trend toward the association of discontinuous pulmonary arteries with a chromosome 22q11 deletion. Interruption of the aortic arch and truncal valve morphology and function did not correlate significantly with the presence of a chromosome 22q11 deletion. In conclusion, a chromosome 22q11 deletion is common in patients with truncus arteriosus, and those with abnormal sidedness and/or branching of the aortic arch are significantly more likely to have a deletion. Clinically important anatomic variables, such as abnormalities of the truncal valve and interrupted aortic arch, were not associated with a chromosome 22q11 deletion in this series. Present address (D.B. McElhinney): Department of Cardiology, Childrens Hospital, Boston, MA     

Intussusception nephrosis and Drash syndrome

A 6-month-old female infant presented with intussusception. Post-operatively she was noted to have nephrotic syndrome. The oedematous bowel wall may have been the cause of the intussusception and this has not been previously described. In addition her karyotype was XY suggesting her nephropathy was associated with Drash syndrome.     

Noonan syndrome: growth and clinical manifestations in 144 cases

We have analysed growth and the major clinical manifestations of 144 patients (89 males, 55 females) with Noonan syndrome from two West German centres. Size at birth was normal in both sexes. In both males and females, the mean height followed along the 3rd per centile until puberty, but decreased transiently due to an approximately 2 year delay in onset of puberty. Final height approaches the lower limits of normal at the end of the 2nd decade of life. The mean adult height was found to be (n=20) 162.5 cm in males and (n=13) 152.7 cm in females, respectively. Smoothed means and standard deviations for height were derived. These data may be used for the statistical evaluation of height of Noonan syndrome patients. Except for mental retardation and microcephaly, which are more frequent in males, the relative frequencies of minor anomalies and malformations were found to be similar in both sexes. The characteristic non-cyanotic heart defects in the Noonan Syndrome do not appear to have a major influence on growth. The auxological data were compared with those in the Ullrich-Turner syndrome.Abbreviation UTS Ullrich-Turner syndrome     

Reye's syndrome developing in an infant on treatment of Kawasaki syndrome

Aspirin is commonly used as an anti-inflammatory therapy for Kawasaki syndrome. Early initiation with high dose aspirin (80 to > 100 mg/kg per day), followed by low-dose therapy at the afebrile stage, has been often used to reduce morbidity and mortality in coronary complications. We report a 10-month-old infant who was diagnosed with Kawasaki syndrome. Sudden onset of poor activity, poor appetite, lethargy, tachycardia, tachypnea, hepatomegaly, increased AST/ALT, coagulopathy and hyperammonemia developed 3 days after the high-dose aspirin therapy. His histopathological and ultrastructural findings from the liver biopsy were compatible with Reye's syndrome. He recovered completely, and there was no recurrence.     

WT1 gene mutations in three girls with nephrotic syndrome

Denys-Drash syndrome and Frasier syndrome are two related conditions caused by mutations of the Wilms tumor gene, WT1. Both syndromes are characterized by male pseudohermaphrodism, a progressive glomerulopathy, and the development of genitourinary tumors. This study examines three girls with steroid-resistant nephrotic syndrome related to mutations in the WT1 gene, but with normal 46, XX karyotype and normal female phenotype. WT1 mutation analysis should be routinely done in females with steroid-resistant nephrotic syndrome.     

儿童Gitelman综合征6例

目的探讨儿童Gitelman综合征的临床特点及其与Bartter综合征的鉴别。方法总结本院住院的6例儿童Gitelman综合征的临床表现、实验室检查、治疗方法及效果,回顾分析Gitelman综合征及Bartter综合征相关文献。分析二者发病机制、临床表现治疗等不同点。结果6例均起病早,婴幼儿期起病,以生长迟缓、无力及抽搐为主要表现,血压正常。实验室检查主要表现低血钾、低血镁,代谢性碱中毒,血浆肾素、血管紧张素明显升高,醛固酮升高不明显或正常。治疗需补钾、补镁症状才能改善。结论Gitelman综合征与Bartter综合征临床表现及发病机制均有不同,相应治疗也不同。     

A Case of Neonatal McCune-Albright Syndrome with Cushing Syndrome and Hyperthyroidism

ABSTRACT. We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T4 276 nmol/l; free T4 125 pmol/l; TSH <1 mU/l; serum cortisol >2210 nmol/l; plasma ACTH < 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3β-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.     

Thoracic insufficiency syndrome: Approaches to assessment and management

Thoracic insufficiency syndrome (TIS) was described in 2003 as the inability of the thorax to support normal respiration or lung growth. TIS includes a broad and disparate group of typically degenerative thoracospinal conditions. Although TIS arises due to a heterogeneous group of disorders and thus its incidence is not well quantified, general approaches to management and treatment exist. Evolving imaging techniques and measurements of health-related quality of life augment tests of pulmonary function to quantify disease burden, longitudinally and pre- and post-intervention. Intervention is primarily via growth-sparing surgery, for which several device options exist, to preserve vertical growth prior to a definitive spinal fusion at skeletal maturity.     

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目的总结偏侧惊厥-偏瘫(HH)综合征和偏侧惊厥-偏瘫-癫癎(HHE)综合征的临床特征.方法对北京大学第一医院儿科1995～2003年收治的11例HH或HHE患儿的临床资料进行分析.11例均做了头颅MRI和(或)CT检查、脑电图(EEG)检查及血生化测定,6例做了尿代谢病筛查.结果8例诊断为HHE,3例诊断为HH.发病年龄1个月至8岁5个月,平均为2岁9个月.4例首次惊厥前伴有发热.5例偏瘫前有惊厥持续状态.5例为右侧偏瘫,6例为左侧偏瘫.头颅影像学显示2例正常,7例大脑半球病变与临床症状相对应,1例为弥漫性病变,1例查出无关病变.11例EEG均为异常,其中8例EEG示双侧半球明显不对称,11例中4例有异常放电.6例代谢癎筛查均为阴性,1例血乳酸、丙酮酸增高,1例血氨增高.7例采用了以卡马西平为主的抗癫癎药治疗.结论HHE为一种公认的惊厥持续状态导致的后遗症,临床上提高对该病的认识并积极进行治疗干预,有助于改善其预后.