Type V acrocephalosyndactylia (Pfeiffer's syndrome). Apropos of 3 cases in the same family

We report 3 cases of acrocephalosyndactyly V (Pfeiffer syndrome) in the same family. This syndrome is characterized by coronal craniosynostosis with facial dysmorphism and specific malformations of the extremities (wide stubly adducted thumbs). The pattern of inheritance in autosomal dominant. The place of this syndrome is discussed in the group of disorders associated with acrocephalopolysyndactyly.     

Acrocephalospondylosyndactyly—A Possible new Syndrome: Analysis of the Vertebral and Intervertebral Components

Apert-Crouzon syndrome (formerly ACS type 2; 10130) is now considered a subset of autosomal dominant Apert acrocephalosyndactyly type 1 (10120), with features of craniosynostoisis, syndactyly of all extremities, maxillary hypoplasia, “parrot-beaked” nose, hypertelorism, exophthalmos, external strabismus, and short upper lip. We report a 3 1/2-month-old infant with features of Apert syndrome, plus thoracic vertebral anomalies radiographically similar to those seen in spondylothoracic dysplasia, a condition in which block thoracic vertebrae with widely open neural arches and a fan-shaped thoracic cage are found. Our patient also had flared metaphyseal ends of humeri, dislocated radii with immobile elbows, an unusual tail-like protuberance in the coccygeal area, and a solid cartilaginous tracheal wall.

To date, in ongoing reviews of radiographs of other patients with acrocephalosyndactyly or acrocephalopolysyndactyly complexes and of relevant literature, we have not identified other patients with these findings.

The vertebrae and intervertebral discs of the patient in this report, three patients with Jarcho-Levin syndrome, and one with Apert syndrome were measured from anteroposterior chest radiographs; the findings clearly distinguish the condition in our patient from Jarcho-Levin syndrome or Apert syndrome.     

Byler's disease (familial fibrogenic cholestasis in children). Apropos of 7 cases

Seven cases presenting with the features of Byler's disease (BD) are reported. The diagnosis of BD can only be made after exclusion of other causes of cholestasis. It seems likely that BD is a syndrome and that more accurate biological and histological investigations will allow to differentiate several entities within this affection. At the present, liver transplantation appears to be the only rational treatment.     

Syndromal Associations of Common Origin of the Carotid Arteries

The term “common origin of the carotid arteries” (COCA) has been proposed to replace the older terms “origin of the left carotid artery from the innominate stem” and “bicarotid trunk with anomalous right or left subclavian artery.” These anatomic patterns are usually reported to occur in about 11% of whites and 20-25% of blacks and have been reported to have increased frequency in patients with esophageal atresia-tracheoesophageal fistula, DiGeorge anomaly, and anomalous origin of the left coronary artery from the pulmonary artery. COCA is a significant, if not invariant, feature of the great arteries in the condition usually called in the more recent literature “anomalous origin of the innominate artery,” the most frequent cause of symptomatic tracheal compression by anomalous systemic arteries. Analysis of associations of COCA with various other congenital cardiovascular lesions showed, in addition, significant association with congenital polyvalvular disease, truncus arteriosus, aorticopulmonary window, trisomy 13, 18, and 21 syndromes, acrocephalosyndactyly (especially Apert syndrome), tetralogy of Fallot not associated with DiGeorge anomaly, and clinical Noonan phenotype. Pentalogy of Cantrell was associated with no increase in incidence of COCA.     

N-acetylaspartic aciduria. Clinical, biological and physiopathological study

Two cases of N-acetylaspartic aciduria in siblings are described and compared to the 18 cases already reported. The disease should be considered in childhood when a syndrome of severe encephalopathy with macrocephaly, blindness caused by optic atrophy and diffuse leucodystrophy on CT scan occurs. Urinary organic acids gas chromatography confirms the diagnosis. It is probably inherited as an autosomal recessive trait. Aspartoacylase activity deficiency has been reported and this assay could possibly be used for prenatal diagnosis. Pathogenesis is not clearly understood but N-acetylaspartic acid (NAA) seems to be essential for central nervous system myelination. Clinical and anatomic features of N-acetylaspartic aciduria are very similar to Van Bogaert-Bertrand disease (cerebral spongy degeneration or Canavan disease) but heterogeneity of this disease cannot excluded.     

Niikawa-Kuroki (Kabuki) Syndrom bei einem 13-jährigen österreichischen Knaben

The Niikawa-Kuroki syndrome is a rare syndrome of multiple congenital anomalies characterized by mainly moderate mental retardation, short stature and a characteristic facial appearence. We report on a 13 y old Austrian boy whose development was handicapped already in the first years by severe failure to thrive due to hypotonia, congenital hydronephrosis, recurrent infections mostly involving the middle ear and delayed motor and speech development. Dentition was complicated and uncomplete. The physiognomy, impressive since early infancy was later on analysed in more detail: bilateral asymmetric ptosis, flat profil with long palpebral fissures, long eye lashes, high arched browes, missing lateral incisors and persistent fetal pads on most of the fingers lead to the Niikawa Kuroki syndrome as the most likely diagnosis, which is to date only clinical. The occurrence is mostly sporadic with some reported cases showing familial resemblance suggesting a dominant fashion of inheritance, the karyotype is normal. Neurological involvement seems to be more severe in the non-Japanese patients this holding true also in our patient.     

Studies of malformation syndromes in man XXXVI: the Pfeiffer syndrome,association with Kleeblattschädel and multiple visceral anomalies

This paper reports sporadic occurrence of the Pfeiffer syndrome with Kleeblattschädel (KS) in a male infant who died at 6 months of pneumonia with signs of increased intracranial pressure and who was found to have hydrocephalus, polymicrogyria, cerebellar herniation, bicuspid aortic valve, a common mesentery, absence of lesser omentum, hypplasia of gallbladder, a single umbilical artery, and multiple eye defects. This case is presumed to represent a new mutation: in other families the Pfeiffer syndrome has been dominantly inherited. The Pfeiffer syndrome is a form of acrocephalosyndactyly and impresses clinically as a mild form of the Apert syndrome. The Kleeblattschädel is an etiologically non-specific developmental field defect (DFC); about two fifths of 51 known cases have apparent thanatophoric dwarfism and about one fifth are probable or possible examples of the Pfeiffer syndrome. The KS-DFC has also been seen in the syndromes of Carpenter, Apert and Crouzon.     

Silver-Russell-Kleinwuchs

Silver-Russell syndrome (SRS) is characterised by severe intrauterine and postnatal growth retardation. Like Prader-Willi and Angelman syndrome it belongs to the increasing class of congenital imprinting disorders. Until recently, the clinical diagnosis of SRS could be confirmed by genetic testing in only <10% of patients. With the identification of disturbed methylation in 11p15 molecular confirmation of the diagnosis is now possible in a further ~38% of cases. In addition, an increasing number of submicroscopic chromosomal disturbances are described based on the application of molecular karyotyping (??DNA chips??). Meanwhile, the same epimutations have been reported in patients with different imprinting phenotypes; an isolated view on a single imprinting disorder is therefore complicated. The reason for this observation is currently unknown, but it seems that similar causes for this group of diseases exist. These causes as well as the pathogenic relationship between (epi)genotype and phenotype currently remain unclear. However, the clinical diagnosis can already be confirmed in ~50% of SRS patients.     

Aberrant muscle syndrome: Hypertrophy of the hand and arm due to aberrant muscles with or without hypertrophy of the muscles

Five patients were reported in our congenital anomaly registry who had six hands in total with muscular hyperplasia, aberrant muscles, ulnar drift of the fingers in the metacarpophalangeal (MP) joints, flexion contractures of the MP joints, and enlargement of the metacarpal spaces. Thirty patients with unilateral involvement of this condition have been reported previously. We reviewed these cases and found that the condition varied in severity and that it was reported using different names. However, this condition seems different from true macrodactyly and multiple camptodactyly, including windblown hand, and seems to be an isolated entity of congenital upper limb anomaly. The authors recommend ‘aberrant muscle syndrome’ or ‘accessory muscle syndrome’ as a diagnostic name, because this seems to be the most common pathological finding in this condition.     

The widened spectrum of multiple cartilaginous exostosis (MCE)

2 brothers with possible homozygous multiple cartilaginous exostosis (MCE) are reported. The MCE-PD-(Peripheral Dysostosis) syndrome is discussed. A family (father, daughter and son) with Metachondromatosis is presented, and the tendency to spontaneous remission in this condition is emphasized. A “second thought”, when considering the diagnosis of MCE, seems worthwhile.     

Mayer-Rokitansky-Kuster-Hauser syndrome: associated pathologies]

MRKH syndrome (Mullerian structures agenesis in woman) is often associated with other anomalies: kidney and bone anomalies, deafness, ovarian tumors. Functional ovarian anomalies have not been previously reported. CASE REPORTS: Five new cases of MRKH syndrome are reported. They were associated with deafness in two cases, with kidney anomaly in three cases, vertebral anomalies in one case, and four suffered from obesity and ovarian dysfunction (ovarian polycystics syndrome, advanced puberty, androgenic excess). All of them had ovarian ectopy, which was responsible for false ultrasonographic diagnosis. CONCLUSION: An MRKH syndrome diagnosis implicates a search for other anomalies. Ovarian functional trouble should not let MRKH syndrome remain unrecognized.     

Acute respiratory distress syndrome in a child with human parvovirus B19 infection

A 6-year-old girl developed shock and multiple organ dysfunction including acute respiratory distress syndrome in association with parvovirus B19 infection. The diagnosis was based on positive antibodies and the detection of parvovirus 19 DNA in serum, bronchial secretions and skin biopsy. It seems likely, but it was not proved, that the parvovirus infection caused acute respiratory distress syndrome.     

Weill-Marchesani syndrome with bilateral angle-closure glaucoma

To our knowledge this is the first reported case of cyclopentolate induced bilateral acute angle-closure glaucoma associated with the Weill-Marchesani syndrome without lens subluxation. The diagnosis of Weill-Marchesani syndrome was not initially suspected, and Pilocarpine was used in an attempt to break the acute attack. Treatment with Pilocarpine-induced myosis only worsened the glaucoma by causing a severe pupillary block. This case is important because it demonstrates that mid-dilatation and cycloplegia can induce acute glaucoma in patients with the Weill-Marchesani syndrome and points out the importance for considering the diagnosis of Weill-Marchesani syndrome in any case of acute glaucoma in childhood.     

Myelodysplastic Syndrome with Partial Deletion of the Long Arm of Chromosome 5: First Report of a Case in a Child

A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q-) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 × 10³/l with 3% atypical lymphocytes, and platelet count 17.7 × 10⁴/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q- in 100% of the metaphases.
These findings led to a diagnosis of MDS with 5q-, which is most commonly found in adult MDS. This case seems to represent an exceedingly rare childhood case of MDS with 5q-.     

Klinefelter's syndrome associated with precocious puberty due to tumoral secretion of chorionic gonadotropins

A 8 and a half year-old boy presented with precocious puberty related to a malignant thoracic teratoma. He was also shown to have a Klinefelter syndrome. Precocious puberty related mainly to the liver, intracranial or thoracic tumors is rare. It seems to be exclusively observed in boys. The slight testicular enlargement is the main clinical sign. The contrast between high LH and low FSH levels is the most striking biological data. The diagnosis is proved by plasma HCG, beta-HCG and alpha-foetoprotein determination. Our patient is the third one with Klinefelter syndrome; this this association is certainly not fortuitous.     

Kidney involvement in autoimmune diseases

New aspects of pathogenesis, diagnosis and treatment of renal involvement in classic generalized immune diseases are reported. In Good-pasture's syndrome survival is now possible with high-dose corticosteroids, cyclophosphamide pulse therapy and plasmapheresis. Renal transplantation can be performed with no recurrence of disease once the production of autoantibodies against basal membranes has stopped. Patients with Wegener's disease die if adequate treatment is not provided. Long-term cyclophosphamide therapy can induce complete remission. A solid-phase radioimmunoassay for detection of circulating autoantibodies to neutrophilic cytoplasmic antigens is helpful in the diagnosis and monitoring of therapy. In systemic lupus erythematosus, renal biopsy is only mandatory to solve the question as to whether high-dose steroid treatment should be prescribed: only in the case of diffuse proliferative glomerulonephritis will corticosteroids be beneficial. Intermittent pulse therapy with cyclophosphamide seems to slow down the progression of renal failure, whereas a positive effect of plasmapheresis has not been proven. Cyclosporin A reduces the dosage of corticosteroids needed.     

Allgrove综合征病例报告及AAAS基因分析

目的报告1例Allgrove综合征,并对患儿及其父母的AAAS基因进行分析。提请医生认识和正确诊断该疾病。方法描述患儿临床特征和遗传特征,进行生化、内分泌激素、影像学、神经电生理、眼底及泪腺检查。提取基因组DNA,特异性片段扩增、测序进行基因分析。结果7岁女童,因呕吐9个月且渐加重而再次住院。5岁时以低血糖昏迷,皮肤发黑而就诊,诊断为爱迪生病并接受治疗。因频繁呕吐9个月再入院。具有四肢肌腱反射明显亢进,视乳头萎缩、无泪症和贲门失弛缓症。患儿父母为三代以外的姨表亲缘关系。基因分析显示：患儿为纯合子AAA基因第8外显子771位硷基G缺失突变,导致ALADIN蛋白移码突变p．R258GfsX33。患儿父母各携带一条正常和一条异常基因。结论Allgrove综合征临床诊断明确。疾病遗传符合常染色体隐性遗传方式。ALADIN蛋白功能对这一综合征非常重要。临床表型与基因突变位点无显著相关性。     

Sanfilippo type C disease: Clinical findings in four patients with a new variant of mucopolysaccharidosis III

A new genetic variant of the Sanfilippo syndrome due to deficiency of acetyl CoA: alpha-glucosaminide N-acetyltransferase, was recently demonstrated in four patients. The clinical findings of these patients are reported here. Differential diagnosis from other types of the Sanfilippo syndrome on clinical and routine laboratory criteria is difficult and enzyme assay is necessary to reach the diagnosis. Since two of the patients reported are females and consanguinity was present in one case, autosomal recessive inheritance is most probable.     

Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome in a Swiss child

Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome is a rare neurodegenerative syndrome first reported in 1991. Most patients described are of Finnish descent and very few patients have been reported in other countries. We report the first Swiss patient who fulfils the criteria of the PEHO syndrome. The course of the epilepsy is less severe than previously reported. Our patient developed a severe dystonic state after a febrile gastrointestinal infection, with a hypotonic state that may have been a dysregulation of brainstem origin. The diagnosis was made because of marked cerebellar atrophy in the repeated MRI. In patients with infantile spasms and severe developmental delay PEHO syndrome should be considered; it is not confined to Finnish heritage. Optic atrophy should be looked for and repeat MRI is indicated.