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Whole-exome sequencing (WES) is increasingly being utilized to diagnose individuals with undiagnosed disorders. Developmental delay and short stature are common clinical indications for WES. We performed WES in three families, using proband-parent trios and two additional affected siblings. We identified a syndrome due to an autosomal-recessively inherited deficiency of transketolase, encoded by TKT, on chromosome 3p21. Our series includes three families with a total of five affected individuals, ranging in age from 4 to 25 years. Two families of Ashkenazi Jewish ancestry were homozygous for an 18 base pair in-frame insertion in TKT. The third family was compound heterozygous for nonsense and missense variants in TKT. All affected individuals had short stature and were developmentally delayed. Congenital heart defects were noted in four of the five affected individuals, and there was a history of chronic diarrhea and cataracts in the older individuals with the homozygous 18 base pair insertion. Enzymatic testing confirmed significantly reduced transketolase activity. Elevated urinary excretion of erythritol, arabitol, ribitol, and pent(ul)ose-5-phosphates was detected, as well as elevated amounts of erythritol, arabitol, and ribitol in the plasma of affected individuals. Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth. NADPH is also critical for maintaining cerebral glutathione, which might contribute to the neurodevelopmental delays. Transketolase deficiency is one of a growing list of inborn errors of metabolism in the non-oxidative part of the pentose phosphate pathway.

Contains fulltext : 97141.pdf (Publisher’s version ) (Closed access) Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears(1)(3). Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities.

The SATB2-associated syndrome (SAS) was recently proposed as a clinically recognizable syndrome that results from deleterious alterations of the SATB2 gene in humans. Although interstitial deletions at 2q33 encompassing SATB2, either alone or contiguously with other genes, have been reported before, there is limited literature regarding intragenic mutations of this gene and the resulting phenotype. We describe five patients in whom whole exome sequencing identified five unique de novo mutations in the SATB2 gene (one splice site, one frameshift, and three nonsense mutations). The five patients had overlapping features that support the characteristic features of the SAS: intellectual disability with limited speech development and craniofacial abnormalities including cleft palate, dysmorphic features, and dental abnormalities. Furthermore, Patient 1 also had features not previously described that represent an expansion of the phenotype. Osteopenia was seen in two of the patients, suggesting that this finding could be added to the list of distinctive findings. We provide supporting evidence that analysis for deletions or point mutations in SATB2 should be considered in children with intellectual disability and severely impaired speech, cleft or high palate, teeth abnormalities, and osteopenia.

We report on six new families (12 new patients) with the syndrome of microcephaly, facial and hand abnormalities, tracheoesophageal fistula, duodenal atresia, and developmental delay. The most common findings were hand abnormalities, microcephaly, short and/or narrow palpebral fissures, broad nasal bridge, anteverted nostrils, ear abnormalities, and micrognathia. Inheritance is autosomal dominant. There is a significant amount of intrafamilial variability especially as it relates to the gastrointestinal findings. Although the first patients reported, who were very young, did not exhibit any developmental delay, they subsequently did develop learning problems, and 87% of our 12 patients had mental retardation or learning difficulties.

Background Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations. Conclusions This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.

Item does not contain fulltext Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of -4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n = 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth. (c) 2012 Wiley Periodicals, Inc.

A 32-year follow-up of the first patient reported with the Floating-Harbor syndrome is discussed. He has been in good overall health. His facial appearance, a hallmark of this syndrome, had remained fairly characteristic except for some changes secondary to age. While he does have mild to moderate mental retardation, he has been employed for the past 15 years. Because no laboratory tests are presently available to diagnose the Floating-Harbor syndrome, the author recommends that the typical facial features present in the first two patients reported with this syndrome be present before the diagnosis can be made.

Hand-foot-genital syndrome (HFGS) is a rare, dominantly inherited condition affecting the distal limbs and genitourinary tract. A nonsense mutation in the homeobox of HOXA13 has been identified in one affected family, making HFGS the second human syndrome shown to be caused by a HOX gene mutation. We have therefore examined HOXA13 in two new and four previously reported families with features of HFGS. In families 1, 2, and 3, nonsense mutations truncating the encoded protein N-terminal to or within the homeodomain produce typical limb and genitourinary abnormalities; in family 4, an expansion of an N-terminal polyalanine tract produces a similar phenotype; in family 5, a missense mutation, which alters an invariant domain, produces an exceptionally severe limb phenotype; and in family 6, in which limb abnormalities were atypical, no HOXA13 mutation could be detected. Mutations in HOXA13 can therefore cause more-severe limb abnormalities than previously suspected and may act by more than one mechanism.

There have been conflicting reports in the medical literature concerning the effect on the family of having a child or sibling with Down syndrome (DS). My own clinical impression, after caring for over 500 children with DS for 30 years, is that parents and siblings of individuals with DS cope quite well, and it is not as disruptive as once thought. Most physicians have not followed up these children and their families longitudinally and, therefore, have not had the opportunity of seeing how well these families adjust to having a family member with DS. In an attempt to gain more information on this subject, the marital status (married, divorced) of our DS parents was used as 1 indicator of marital harmony or discord. Initially, in an informal fashion, 551 questionnaires were mailed to DS parents and 279 were returned completed (a 50.6% response rate). A variety of questions were asked

We report on a mother and daughter with the Brachmann-de Lange syndrome which supports the view that in some families this disorder is due to autosomal dominant inheritance. A review of the literature concerning autosomal and recessive inheritance of this syndrome is presented.

Sir. —Although "mongolism" and "mongoloid" slant of the eyes have been replaced by the more accurate terms Down syndrome and upslanting palpebral fissures , the term mongolian spot persists in common pediatric usage. 1-7 This benign, blue-gray macule occurs frequently in infants of Asian, Mediterranean, and African heritage. Anthropologic theories have attempted to explain the origin of this spot, suggesting that it was derived from the racial admixture resulting from the Mongolian invasion of Europe. 8 It had been noted that the spot was more common in "Mongolian" nonwhite races, hence the appellation. However, not all Asian people are derived from Mongolian tribes and, conversely, not all Mongolians are Asian. Pediatric textbooks have commented that the term mongolian spot is "... an unfortunate name for such a common benign skin discoloration," 5 and this lesion has "... no known anthropological significance." 7 We suggest that mongolian spot be replaced with blue-gray macule of

We performed examinations and echocardiographic studies in 35 patients with Down syndrome (aged 20 +/- 4.2 years) with no known intracardiac disease. Sixteen patients (46%) had mitral valve prolapse; two of these also had tricuspid valve prolapse. Two had aortic regurgitation. Valve regurgitation was present in 4 (17%) of 23 patients more than 18 years of age but in none of the 12 patients 18 years of age or younger. We recommend screening of adolescent and young adult patients with Down syndrome for the development of valve dysfunction, especially before dental or surgical procedures.

We report on 2 unrelated patients with microcephaly, lymphedema, and chrorioretinal changes. They are compared with previously reported patients with microcephaly and lymphedema and microcephaly with chorioretinal changes. The question is raised whether all of these patients represent one entity or are separate syndromes. Until more data are available we propose that our patients represent a single entity. © 1992 Wiley-Liss, Inc.

In Reply. —Mallory disagrees with my final statement concerning the treatment of patients with Down syndrome who have syringomas. Unfortunately, she did not quote the entire sentence, which states "It is important for pediatricians to be aware of the significance of syringomas in patients with DS so that they can inform the patient and family of the benign nature of these lesions and not subject the patient to an unnecessary evaluation." This sounds like a very noncontroversial statement to me. Mallory's apparent concern is that most of the diagnoses of syringomas were made on clinical examination and "none of these patients underwent a biopsy of these lesions for verification of the diagnosis." If Mallory believes it is necessary for all such patients to undergo a biopsy, I strongly disagree. In the beginning of our study we did perform biopsies in some of our patients to confirm the diagnosis. We discontinued this practice

This is the second edition of this color atlas. Most of the 14 chapters discuss specific organ systems, although there are chapters on the newborn, congenital anomalies, metabolic diseases, and nutritional disorders. It is especially important that before purchasing this book, you are aware of what it does and does not provide. There are 702 excellent color photographs covering a large number of pediatric diseases. Its main drawback, however, is superficiality. The authors dostate, "A comprehensive discussion of every conceivable symptom was not our intent," and "Medical students can use the book as a supplement to a basic text." These admonitions are very valid. A good example is the six lines and one photograph concerning the Goldenhar syndrome. The photograph demonstrates a right preauricular appendage, macrostomia, and a fair view of mandibular hypoplasia. This could represent hemifacial microsomia (most researchers believe they may be the same condition), and although the

A family exhibiting a leukocytic arylsulfatase A deficiency, probably inherited in an autosomal recessive manner, differed from patients with typical metachromatic leukodystrophy in that sulfatiduria was absent and there was readily detectable cerebroside sulfatase activity. To our knowledge, this family was unique in that there were no known members with metachromatic leukodystrophy and the only neurologic abnormality was progressive retinal pigment degeneration in the proband.

tive study of unexplained nausea and vomiting after marrow transplantation. Transplantation 1986;42:602-7. 4. Spencer GD, Shulman HM, Myerson D, Thomas ED, McDonald GB. Diffuse intestinal ulceration after marrow transplantation: A clinicopathologic study of 13 patients. Hum Pathol 1986;17:621-33. 5. Pass RF, Whitley R J, Diethelm AG, Whelchel JD, Reynolds DW, Alford CA. Cytomegalovirus infection in patients with renal transplants: Potentiation by antithymocyte globulin and an incompatible graft. J Infect Dis 1980;142:9-17. 6. Converse P, Hess A, Tutschka P, Santos GW. Effect of cyclosporine on the response of normal human lymphocytes to cytomegalovirus in vitro. Infect Immun 1983;41:1226-33. 7. Chachoua A, Dieterich D, Krasinski K, et al. 9-(1,3-dihydroxy-2-propoxymethyl) guanine (gancyclovir) in the treatment of cytomegalovirus gastrointestinal disease with the acquired immunodeficiency syndrome. Ann Intern Med 1987;107:1337. 8. Weber JN, Thorn S, Barrison I, et al. Cytomegalovirus colitis and oesophageal ulceration in the context of AIDS: Clinical manifestations and preliminary report of treatment with Foscarnet (phosphonoformate). Gut 1987;28:482-7. 9. Rakela J, Wiesner RH, Taswell HF, et al. Incidence of cytomegalovirus infection and its relationship to donor-recipient serologic status in liver transplantation. Transplant Proc 1987; 19:2399-2402. 10. Snydman DR, Werner BG, Heinze-Lacey B, et al. Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med 1987;317-1049-54.

We studied a family of Portuguese ancestry from the Azores who suffered a progressive neurologic disease characterized by gait ataxia, features similar to Parkinson's disease in some patients, limitation of eye movements, widespread fasciculations of muscles, loss of reflexes in the lower limbs, followed by nystagmus, mild cerebellar tremor and extensor plantar responses. Two post-mortem examinations revealed loss of neurons and gliosis in the substantia nigra, nuclei pontis (and in the putamen in one case) as well as in the nuclei of the vestibular and other cranial nerves, columns of Clarke and anterior horns, in the spinal cord there were also loss of fibers in the fasciculi gracilis and mild changes in the pyramidal tracts. Comparison of the disease in this family with the findings reported in three families of similar ancestry, previously thought to have different disorders, suggests that they may all represent a single genetic entity with variable expression.

Twenty-four children with cutaneous hemangiomas were treated with corticosteroids. The indications for therapy included interference with im portant bodily functions by the hemangioma, thrornbocytogenia related to the hemangioma, or serious cosmetic effects secondary to the hemangioma. Five children had no improvement, twelve had possible improvement, five had probable improvement and two had definite improvement while on cortico steroids. One child had growth retardation as a complication of corticosteroids; this was reversed when the medication was discontinued.

As the role of the pediatrician changes, less time will be devoted to routine care and more time will be spent in other areas such as genetics and birth defects. Approximately 5% of all newborn babies have a significant birth defect requiring the care of a pediatrician. Structural abnormalities such as meningomyelocele, cleft palate, limb abnormalities, and other obvious defects usually do not present any diagnostic problems. However, there may be difficulty in diagnosis of the child who has nonspecific findings such as an unusual facial appearance and/or minor congenital anomalies. In this situation, the pediatnician must first decide whether the child is normal or abnormal; at times this may be difficult. If abnormal, then the correct diagnosis must be ascertained in order to provide the family with genetic counseling, a prognosis, and treatment when available. Complicated medical gadgetry may be helpful in making a diagnosis, but a thorough history and physical examination remain the clinician's key to unlocking a diagnostic dilemma. A family pedigree should be constructed listing any significant illnesses, birth defects, chromosomal abnormalities, consanguinity, and mental retardation. A complete pregnancy history should always be obtained; what took place during the mother's pregnancy also affected the boarding fetus. Queries should be made concerning exposure to drugs, alcohol, infections, environmental contaminants, and radiation.

The first patient with trisomy 9, an infant who survived 28 days, is reported. Clinical findings included microcephaly, low-set malformed ears, small palpebral fissures, enophthalmos, bulbous nose, micrognathia, low hairline, congenital heart disease, skeletal abnormalities, small penis, hypoplastic scrotum, and a Dandy-Walker like deformity of the fourth ventricle.

IN 1948 Warkany and Hubbard1 indicted mercury ingestion as an etiologic factor in acrodynia. Other reports establishing mercury as the most important cause of acrodynia soon followed.2 3 4 5 6 7 8 Dimercaprol (BAL), which chelates mercury, was quickly introduced as a therapeutic agent in 1948 but has given variable results.6 , 9 10 11 12 13 14 15 Edathamil calcium disodium (EDTA) when given for therapy of acrodynia did not significantly increase mercury excretion.16 Increased urinary elimination of mercury during penicillin therapy for infection has been observed,17 but the results of penicillin therapy in acrodynia have been equivocal.17 , 18 Aposhian19 , 20 has shown that N-acetyl-D,L-penicillamine is more effective than other penicillamine derivatives in protecting . . .

Three generations of a family with Rieger's syndrome are presented. Ocular and dental abnormalities constitute the major manifestations. Hypodontia, microdontia, enamel hypoplasia, missing teeth, peg-shaped teeth, and malocclusion are frequent oral findings. Hypoplasia of the maxilla causes the mandible to appear prominent, giving the patient a prognathic appearance. Aniridia, hypoplastic iris, and glaucoma are the major eye problems. The propositus also has short stature and decreased growth hormone levels which have not been reported before in this syndrome. The importance of early diagnosis is stressed in order to preserve the remaining dentition by proper dental care and to be aware of the possibility of the presence of glaucoma, which should be treated as soon as discovered.

Eight patients are presented who have a particular type of "Hurler"-like bodyconfiguration, severe skeletal dysplasia, severe psychomotor retardation, and normal urinary excretion of acid mucopolysaccharides, constituting in the sum a new entity, here designated as "I-cell" disease (or mucolipidosis II). The condition is evident from birth, with gradual accentuation of clinical features, complicated by respiratory infections, and with a fatal outcome. Familial occurrence in two instances and parental consanguinity in one, make autosomal recessive mode of inheritance most likely. Fibroblasts of these patients show an abundance of special cytoplasmic inclusions ("I cells"), have numerous deficiencies in lysosomal hydrolases, and contain excessive amounts of lipids and mucopolysaccharides. Results obtained on analysis of liver and brain specimens have less notable abnormalities. The pathogenesis of this new syndrome remains unknown. It must be differentiated especially from the Hurler's disease, G M1 -gangliosidosis type 1, and lipomucopolysaccharidosis.

Four cases of oculoauriculovertebral dysplasia (Goldenhar's syndrome), consisting of epibulbar dermoid tumors, preauricular appendices, ear deformities, and vertebral anomalies, are described. The oral manifestations of the syndrome are enumerated in each case. The differential diagnosis of oculoauriculovertebral dysplasia, mandibulofacial dysostosis (Treacher Collins syndrome), and hemifacial microsomia is outlined. The multidisciplinary treatment of the eye, ear, face, and oral abnormalities is discussed.

Summary Thirty-two unrelated patients with features of Saethre-Chotzen syndrome, a common autosomal dominant condition of craniosynostosis and limb anomalies, were screened for mutations in TWIST,FGFR2, and FGFR3. Nine novel and three recurrent TWIST mutations were found in 12 families. Seven families were found to have the FGFR3 P250R mutation, and one individual was found to have an FGFR2 VV269–270 deletion. To date, our detection rate for TWIST or FGFR mutations is 68% in our Saethre-Chotzen syndrome patients, including our five patients elsewhere reported with TWIST mutations. More than 35 different TWIST mutations are now known in the literature. The most common phenotypic features, present in more than a third of our patients with TWIST mutations, are coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, ptosis, hypertelorism, broad great toes, and clinodactyly. Significant intra- and interfamilial phenotypic variability is present for either TWIST mutations or FGFR mutations. The overlap in clinical features and the presence, in the same genes, of mutations for more than one craniosynostotic condition—such as Saethre-Chotzen, Crouzon, and Pfeiffer syndromes—support the hypothesis that TWIST and FGFR s are components of the same molecular pathway involved in the modulation of craniofacial and limb development in humans.

PubMed ID: 14508707, Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are autosomal recessive conditions characterized by multiple subcutaneous skin nodules, gingival hypertrophy, joint contractures, and hyaline deposition. We previously mapped the gene for JHF to chromosome 4q21. We now report the identification of 15 different mutations in the gene encoding capillary morphogenesis protein 2 (CMG2) in 17 families with JHF or ISH. CMG2 is a transmembrane protein that is induced during capillary morphogenesis and that binds laminin and collagen IV via a von Willebrand factor type A (vWA) domain. Of interest, CMG2 also functions as a cellular receptor for anthrax toxin. Preliminary genotype-phenotype analyses suggest that abrogation of binding by the vWA domain results in severe disease typical of ISH, whereas in-frame mutations affecting a novel, highly conserved cytoplasmic domain result in a milder phenotype. These data (1) demonstrate that JHF and ISH are allelic conditions and (2) implicate perturbation of basement-membrane matrix assembly as the cause of the characteristic perivascular hyaline deposition seen in these conditions., Institute of Cancer Research Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung: 3100A0–100485 Medical Research Council, We thank all the members of the families, for their invaluable contribution to this research; N. Akarsu, T. Ball, C. Black, P. Byers, T. Hamada, M. McAvoy, J. Power, J. Prendiville, and V. Wessagowit, for assistance in obtaining samples; and A. Bateman, at the Wellcome Trust Sanger Institute, for initial Pfam analysis of CMG2. M.E.C. and F.M.P. are supported by the Medical Research Council and the Ehlers-Danlos Support Group. A.S.F. is supported by the Swiss National Science Foundation (3100A0–100485). This work was supported by Institute of Cancer Research (U.K.).

IT has generally been assumed that viruses are involved in the pathogenesis of otitis media either as primary agents or as antecedents of bacterial infections, but neither of these possibilities has been well documented. This report presents the results of attempts to isolate viruses and mycoplasmas from middle-ear fluids obtained by needle aspiration in 90 children with acute otitis media, and results of serologic studies using 18 viral antigens and a Mycoplasma pneumoniae antigen in 73 of these children. The results of bacteriologic studies of the middle-ear fluids, throat and nasopharynx and a discussion of the clinical findings have been . . .

IN 1955 Benirschke and Brown1 reported extensively on the occurrence of congenital anomalies in association with the absence of one of the two umbilical arteries. This study, together with previous and subsequent investigations, has stimulated interest in the value of this defect as a means of early recognition of neonatal malformations. Prospective studies (Table 1) have shown the incidence of single umbilical artery to vary from 0.2 to 1.3 per cent in consecutive single births and from 0 to 7 per cent in twin births.2 3 4 5 The frequency of congenital anomalies in such series has ranged from 20 to 47 per . . .

A pathologic study of the first case of trisomy 9 is presented. The patient, a 26 day old male infant, was found at autopsy to have primarily cardiovascular, liver, brain, and skeletal abnormalities. The cardiac findings included double outlet right ventricle, preductal coarctation of the aorta, patent ductus arteriosus, and ventricular septal defect. Skeletal anomalies consisted of lack of a pubic arch, hypodevelopment of the left tibia, absence of the left fibula, missing tarsal and calcaneal bones bilaterally, a left foot having a single toe with a metatarsal and two phalangeal bones, absence of the distal phalangeal bones of four toes on the right foot, bilateral radial head dislocations, and micrognathia. Liver findings included bile duct proliferation, canalicular cholestasis, mild portal mononuclear inflammatory infiltrate, and fatty change in the absence of biliary tract obstruction. Findings in the brain included a large fourth ventricle between widely separated cerebellar hemispheres, which suggested the Dandy-Walker malformation. The cerebellum, however, was well formed histologically and the roofing membrane appeared to be arachnoid.

The Coffin-Siris syndrome is no humbug! Therefore, the practicing pediatrician should add this syndrome to the already long list of syndromes he has to consider when evaluating a child with mental retardation. Because the pediatrician in practice cannot remember all the existing syndromes (neither can the "syndromologist"), it is important that he has an organized approach to the differential diagnosis of such children. The first step is to do a thorough See also p 667. history and physical examination. A genetic history should be a routine part of the initial history done by a pediatrician on all patients. Since it is time consuming, we recommend that before the child is seen by the pediatrician the parents fill out a genetic history form including a family pedigree. This not only saves time but it is usually more accurate as it provides the family an opportunity to discuss the "family tree" with

Familial aggregates of incomplete Mullerian fusion have been reported, but the role of genetic factors has not been elucidated. In the last several years, we have fortuitously encountered three families in which several members were affected with Mullerian fusion anomalies. In two families, several members had incomplete Mullerian fusion as traditionally described. In the third family, several members had the hand-foot-genital syndrome, a rare autosomal dominant disorder characterized not only by Mullerian fusion defects but also by skeletal (hand and foot) malformations. The etiologic heterogeneity of Mullerian fusion defects is considered.

The presence of a growth abnormality may be documented by determination of growth velocity, calculation of the upper segment/lower segment ratio or the AF/AT ratio, and measurement of head circumference. Important considerations in differential diagnosis of specific malformation syndromes are birth weight, limb and truck alterations, head size, physical features, and presence or absence of mental retardation. Additional clinical measurements, such as measurement of chest circumference and of finger and hand length, may be useful in selected cases. These data, combined with historical information, can indicate a specific diagnosis and facilitate the choice of confirmatory laboratory studies.

A Syndrome Identification and Consultation Service has been moderately successful as a method in the diagnosis of the unusual looking child. A definite diagnosis was made in 18% of the first 100 cases. In cases in which a definite diagnosis was not made, the consultants entertained some type of diagnosis in 35%.

Seven cases of the Beckwith-Wiedemann syndrome are reported. The features of the syndrome may include macroglossia, omphalocele or umbilical hernia, visceromegaly, postnatal gigantism, microcephaly, nevus flammeus, ear lobe grooves, diaphragmatic eventration, hemihypertrophy, and other abnormalities. The anomalies of the syndrome are facultative and not obligatory. Early diagnosis of this striking syndrome alerts the clinician to the dual threat of possible hypoglycemia and various malignant neoplasms. Although observation of the disorder in sibs suggests autosomal recessive inheritance, several pedigrees intimate that the syndrome is inherited in an autosomal dominant fashion with incomplete penetrance and variable expressivity. For the purposes of genetic counseling, a careful search for minor anomalies of the syndrome should be undertaken in relatives of the proband.