Definition and diagnosis of the Brachmann-De Lange syndrome

We have classified patients referred for suspicion of the Brachmann-De Lange syndrome (BDLS) into two groups using techniques of numerical taxonomy. Patients with the syndrome share an array of abnormal characteristics, and those without it have different abnormal characteristics. A group of 30 characters that best distinguish the two groups of patients was used to construct a diagnostic index. The index score is expected to divide 99% of patients into those with and without the syndrome, leaving 1% in a "zone of doubt." All 46 patients used to construct the index and 16 new patients had scores in either the BDLS or non-BDLS range and none were in the zone of doubt. A previously published index using metacarpal-phalangeal measurements, although less discriminatory, confirmed our findings in 84% of 25 patients tested, the remainder having scores in the zone of doubt for that index.     

Metacarpophalangeal pattern profile analysis in Brachmann-de Lange syndrome

We analyzed the metacarpophalangeal pattern profile (MCPP) of 19 individuals with Brachmann-de Lange syndrome (BDLS) and calculated a mean syndrome profile. Fourteen of 19 individuals with BDLS had significant positive correlations which indicated clinical homogeneity. Discriminant analysis of individuals with BDLS compared with a sample of normal individuals produced a correct classification rate of 100% based on a function of 2 MCPP variables that may provide a useful tool for assisting in the diagnosis of BDLS. An average pattern variability index calculated for the BDLS patients was 1.9 indicating an abnormal hand pattern in this syndrome. © 1993 Wiley-Liss, Inc.     

Diagnosing of chromosome abnormalities in Denmark

Fifty-two patients referred for suspicion of the Williams syndrome have been evaluated and divided into those with and without the syndrome by numerical analysis. A diagnostic index using 50 characters separates patients into two groups with an expected accuracy of 99%. An index using 40 of the characteristics is expected to be applicable to young infants without a substantial decrease in accuracy.     

Clinical variability within Brachmann-de Lange syndrome: A proposed classification system

Seven patients, including two sibs, with the Brachmann-de Lange syndrome (BDLS) are presented as representative of the different types of BDLS in a proposed classification system. Type I (“classic”) patients have the characteristic facial and skeletal changes of BDLS using the criteria in the diagnostic index of Preus and Rex. Type I is distinguished from the other subtypes by prenatal growth deficiency (< 2.5 S.D. below mean for gestation) becoming more severe postnatally (< 3.5 S.D. below the mean), moderate to profound psychomotor retardation, and major malformations which result in severe disability or death. Type II (“mild”) BDLS patients have similar facial and minor skeletal abnormalities to those seen in type I; however, these changes may develop with time or may be partially expressed. Patients with type II BDLS are distinguished from those with other types by mild to borderline psychomotor retardation, less severe pre-and postnatal growth deficiency, and the absence of (or loss severe) major malformations. Behavioral problems can be a significant clinical problem in type II BDLS. Type III (“phenocopies”) BDLS includes patients who have phenotypic manifestations of BDLS which are causally related to chromosomal aneuploidies or teratogenic exposures. © 1993 Wiley-Liss, Inc.     

Variability of the Brachmann-de Lange Syndrome

Brachmann-de Lange syndrome (BDLS) is a relatively common multiple congenital anomaly/mental retardation syndrome, whose cause is unknown. The clinical variability of this condition is well-known. Recently some reports suggested the possible existence of a mild BDLS phenotype. We report on 30 patients in whom a diagnosis of BDLS was made or strongly suspected in 12 different Italian hospitals. Based on clinical evaluation we divided them into two groups, classical and mild BDLS cases. We compare the clinical data of these patients and we discuss the problems which arise in trying to define clear criteria of distinction between these two groups. © 1993 Wiley-Liss, Inc.     

Brachmann-de Lange syndrome (BDLS) with asymmetry and skin pigmentary anomalies: a result of mosaicism for a putative bdls gene mutation?

Brachmann-de Lange syndrome (BDLS, OMIM 122470) is a rare malformation syndrome characterized by mental retardation, short stature, limb abnormalities, and a distinctive craniofacial appearance. There is wide clinical variability and mildly affected patients are common. The genetic basis of BDLS and the reasons for its phenotypical variability are still unknown. We report on a patient with mild BDLS and the unusual findings of asymmetric growth of one body half and irregularly shaped pigmentary anomalies of the skin. These two traits have not been previously described in BDLS but have been associated with phenomena of genetic mosaicism in other conditions. We suggest that this patient's phenotype could be the result of mosaicism for a mutation or submicroscopic deletion affecting one or several genes responsible for BDLS.     

Mild mental retardation with classic somatic phenotype in the Brachmann-de Lange syndrome

Severe Mental retardation is the most handicapping disability for individuals with Brachmann-de Lange syndrome (BDLS). Reports of higher functioning patients with suspected BDLS have invariably described those with a “mild” BDLS somatic phenotype. Here we report on 2 high-functioning females, ages 3.7 and 10.6 years, with the classic BDLS somatic phenotype, i.e., all growth parameters at 4–5 standard deviations bellow the mean prenatally and postnatally. These 2 patients serve to extend the spectrum of classic BDLS to include cognitive function in the mild-to -moderate range of mental retardation. © 1993 Wiley-Liss, Inc.     

Prometaphase chromosomes in five patients with the Brachmann-de Lange syndrome

We analyzed the prometaphase chromosomes of 5 patients (including one pair of sibs) with the Brachmann-de Lange syndrome (BDLS), and did not find a significant chromosome abnormality in any of them. It appears that two distinct entities can be distinguished on clinical and chromosomal bases: the BDLS and the dup(3q) syndrome. We still recommend chromosome studies in any patients with BDLS and BDLS-like manifestations.     

Fetal biometry in the Brachmann-de Lange syndrome

The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established rations of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of “small for gestational age” would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length ) in 4 of the 11 fetuses where such information could be obtained. BDLS fetuses demonstrate early and symmetric intrauterine growth retardation. We conclude that fetal biometry can provide a valuable index in the assessment of a pregnancy suspected to be at risk for a severely affected BDLS child. © 1993 Wiley-Liss, Inc.     

Mild Brachmann-de Lange syndrome. Phenotypic and developmental characteristics of mildly affected individuals

Since 1981, we have identified 3 patients with mild Brachmann-de Lange syndrome (BDLS) who have had subtle but definite manifestations of the syndrome and mild effects on growth and development. J.G. (B.D. 12/9/72) was first examined at 20 months. He had rather typical craniofacial findings and hirsutism, limitation of full supination of his arms, and brachyclinodactyly of the 5th fingers. IQ was estimated at 65. K.H. (B.D. 10/10/83) was first examined by us at age 9 months and was diagnosed as having “mild” BDLS. At age 5, K.H. has demonstrated relatively normal cognitive development (low average–average IQ of 74) with specific learning problems: weakness of visual-motor skills, delayed expressive language development, and articulation difficulties. At age 7, he was attending a regular 1st grade classroom, with some special education assistance. M.E.(B.D. 4/19/78) was diagnosed at age 10 years as having “mild” BDLS. His physical changes were more subtle than those of the 2 patients above. At age 10, M.E. was in the regular 4th grade classroom receiving special education support. His IQ was in the borderline-low-average range. He had strengths in rote verbal skills, with weaknesses in reading and writing. These 3 patients demonstrate mild BDLS in which characteristic manifestations of the syndrome, particularly craniofacial anomalies, are present and recognizable, but quite subtle, thus making the clinical diagnosis difficult. In addition, the milder physical phenotype is associated with milder cognitive and behavioral consequences. When comparing patients with mild BDLS to those in our practice (4 others) with typical changes, we find that birth weight, absence of major anomalies, and subtlety of craniofacial abnormalities are predictive of mildly affected patients. © 1993 Wiley-Liss, Inc.     

A diagnostic index for Down syndrome

A simple and effective index for the diagnosis of Down syndrome is presented. It makes use of 12 characters with from two to nine states. The simple format allows persons with limited knowledge of the characters to use it. Simplicity was attained by combining character states when this did not result in a loss of discrimination and by avoiding characters that were redundant, subject or difficult to evaluate. A combination of characters that occur frequently in Down syndrome (wide applicability and characters that have a high relative frequency (high probability) was used. Additional data from comparable samples were used to calculate more representative scores for some characters. Over 82% of suspected cases may be diagnosed as having or not having Down syndrome with 99.9% confidence. Conditional probabilities for the various scores are provided. Individuals whose scores are in the Down or non-Down zones have a 98.7% probability or greater of having or not having the syndrome, respectively. The index is more effective than others as measured both by the percentage of individuals with and without Down syndrome whose scores fall into distinct zones (overlap method) and by the percentage with Down syndrome who have positive scores and controls who have negative scores (single point classification).     

Partial duplication of 3q (q25.1→q26.1) without the Brachmann-de Lange phenotype

Partial duplications of chromosome 3 have previously been reported to have phenotypic characteristics similar to Brachmann-de Lange syndrome (BDLS). We present the case of a 13-Year-old girl with an apparent duplication in the 3q25.1→q26.1 region but none of the manifestations commonly seen in BDLS. The chromosome 3 duplication was confirmed with a FISH painting probe of the involved region. These results suggest that the region critical for Brachmann-de Lange syndrome is not within the duplicated region of 3q25.1→q26.1. © 1993 Wiley-Liss, Inc.     

癫痫伴发焦虑抑郁患者脑神经递质活动的脑电超慢涨落图表现分析

目的:探讨癫痫伴焦虑抑郁患者脑神经递质活动的脑电超慢涨落图（EFG）表现并对其进行分析。 方法:以2014年1月~2015年12月我院治疗的30例癫痫伴焦虑抑郁患者（记为观察组）、同期于我院治疗的30例癫痫患者（无焦虑抑郁者记对照组）为对象,采用EFG分析仪检测两组研究对象脑内神经递质活动变化情况、脑功能状态差异。 结果:观察组仅5-HT较对照组明显低,其它指标两组之间比较无明显差异（P>0.05）;两组运动指数、兴奋抑郁指数及血管舒缩指数由高至低排序为:观察组＞对照组,两组之间比较差异显著（P<0.05）。 结论:癫痫伴焦虑抑郁患者的EFG表现为脑神经递质的活动异常、脑功能状态处于异常状态,而这些异常表现有助于癫痫伴焦虑抑郁的鉴别诊断。     

多囊卵巢综合征患者的糖代谢特点分析

目的 研究多囊卵巢综合征（PCOS）患者的糖代谢特征。方法 选择2014年1月~2018年3月我院收治的符合鹿特丹标准、未经治疗的PCOS患者935例,测定身高、体重,并行口服葡萄糖耐量试验（OGTT）和胰岛素释放试验（IRT）,计算体重指数（BMI）、胰岛素抵抗稳态指数模型（HOMA-IR）、β细胞功能指数（HOMA-β）等参数。根据血糖水平将 PCOS 患者分为糖代谢正常（NGT）组、空腹血糖受损（IFG）组、糖耐量受损（IGT）组、混合型糖耐量受损（CGI）组及糖尿病（T2DM）组;根据体重指数     

The predictive value of dermatoglyphic anomalies in the diagnosis of fra(X)-positive Martin-Bell syndrome (MBS)

In a representative group of 160 institutionalized mentally retarded males without Down syndrome, prospective dermatoglyphic-cytogenetic studies were performed in order to assess the utility of the dermatoglyphic index system of Rodewald [1986] for an efficient ascertainment of patients with Martin-Bell syndrome (MBS). A negative (abnormal) score was found in 32 men (20 +/- 3%), 14 of whom (predictive value: 44 +/- 9%) were fra(X)-positive. This prevalence of 14/160 = 9 +/- 2% patients with fra(X)-positive MBS indicates that in our study most, if not all, MBS patients have been detected by the simple pre-screening of dermatoglyphics. In the MBS patients, there was no correlation between the dermatoglyphic scores and percentage of fra(X)-positive cells.     

Brachmann-de Lange syndrome: Autosomal dominant inheritance and male-to-male transmission

We report on familial occurrence of the Brachmann-de Lange syndrome (BDLS): a mildly affected father and his severely affected son and daughter who have different mothers. Both children are severely affected while the father has a much milder but definite BDLS phenotype. Our report documents the third example of male-to-male transmission and adds to the argument against exclusively maternal transmission in familial cases. In addition, our findings illustrate the occurrence of severe manifestations in cases of familial BDLS. © 1996 Wiley-Liss, Inc.     

Neonatal-onset panhypopituitarism in a girl with Brachmann-De Lange syndrome

We report on a girl with recurrent hypoglycemia since age 2 days and severe impairment of physical and neurological development. Panhypopituitarism was recognized at age 5 months. The diagnosis of Brachmann-De Lange syndrome (BDLS) was also made. Replacement therapy has avoided further episodes of hypoglycemia, improved growth, and allowed partial psychomotor catch-up. Though we are not aware of any other report of panhypopituitarism in patients with BDLS, we suggest that hormonal derangement may play a role in the manifestations of this syndrome.     

Sixty-four patients with Brachmann-de Lange syndrome: a survey

We surveyed 64 individuals with the diagnosis of Brachmann-de Lange syndrome (BDLS) to determine the natural course and cause of the disorder. The 64 individuals were ascertained through membership in a national organization, the Cornelia de Lange Syndrome (CDLS) Foundation, comprised of families who have a relative with BDLS. We surveyed 64 families by questionnaire and personally examined 24 of the 64. Our data suggest that lower birth weight correlates with a more severe phenotype, specifically including severe upper limb malformations and greater psychomotor retardation. The lower birth weight group showed a significant excess of females. The miscarriage rate was normal and there were no recurrences reported in the 64 families we surveyed. Major management problems included feeding problems and projectile vomiting, behavioral problems including frequent tantrums, hearing and dental difficulties, and recurrent respiratory tract infections. The oldest, teenaged subjects in our study entered puberty; although pregnancy has not been reported in the syndrome, it is likely that people with BDLS are fertile. Though most BDLS children reared at home survive through adolescence, a significant degree of psychomotor retardation and difficult medical management problems still occur.     

Gastrointestinal abnormalities: A significant cause of feeding difficulties and failure to thrive in Brachmann-de Lange syndrome

Gastroesophageal abnormalities occur with increased frequency in patients with Brachmann-de Lange syndrome (BDLS) and contribute to problems with feeding, emesis and failure to thrive. Comprehensive evaluation including longitudinal assessment of growth and development of 8 patients with BDLS was performed. Clinically significant feeding problems occurred in 6 of the 8 patients and the affected children were subsequently evaluated for gastrointestinal abnormalities. Findings in these patients included tracheal aspiration, esophageal dysmotility, gastroesophageal reflux, hiatal hernia, and esophagitis. Medical treatment was instituted where appropriate, and surgical treatment was performed if the problems did not resolve with medical treatment. Improvement in weight centiles occurred in all patients fed by nasogastric or feeding gastrostomy tube but only one patients appeared to experience increase in rate linear growth. Careful monitoring of symptoms and growth parameters, and prompt institution of appropriate medical and surgical measures can improve the health and physical outcome of many patients with BDLS. © 1993 Wiley-Liss, Inc.     

Fragile-X syndrome III: dermatoglyphic studies in males

Dermatoglyphics of 39 males with the fragile-X syndrome were compared with those of 3 groups of control subjects; 497 school boys, 15 males with non-specific mental retardation, and 15 with Down syndrome. Compared with the control males, there was an increased frequency of radial loops, whorls, and arches on the fingers and of third interdigital patterns and abnormal creases on the hands, and a decreased frequency of ulnar loops and fourth interdigital patterns in the patients with the fragile-X syndrome. The mean a-b ridge count was lower than in controls and there were more patients than controls with an a-b ridge count less than 70. All of these differences were significant at p less than 0.01. There was no differences between patients and controls with respect to total ridge count on the fingers and the dermatoglyphics in other areas of the hands or feet. From this small study a preliminary index was developed that attempts to distinguish male patients with the fragile-X syndrome from normal male controls and males with non-fragile-X forms of mental retardation. The patterns on the left and right third fingers, the a-b ridge count, and the palmar creases were used in the index. Sixty-four % of patients with the fragile-X syndrome would be selected out if greater than or equal to + 0.5 was used as the criterion and 90% of these males would be expected to have the fragile-X chromosome.