Multiple Minor Anomalies Research Articles

Cleft Lip Case in a Middle Bronze Age Young Man from Altai, Russia

Oral cleft (OC) is a common congenital anomaly in humans, which occurs in approximately one per 700 live births. However, cleft skulls are found relatively seldom in archaeological specimens, especially for the bc period. Mortality of infants with OC was apparently high because of breastfeeding difficulties and culturally sanctioned rejection of them in the past. This paper presents one of the most ancient cases of OC in Eurasia. The finding comes from the Middle Bronze Age pastoralists' cemetery in Altai, Russia. The skeletal remains have been radiocarbon dated to 1883–1665 cal bc. Cranial and dental measurements, computed tomography and radiography have been used to examine this malformation. The facial sculpting reconstruction has been performed to visualise the ante mortem appearance of the cleft face. Besides, δ13C and δ15N isotope analysis was used for a comparative study of the diet of the cleft individual. It has been established that a young man from Altai was affected by complete bilateral cleft lip and alveolus, which is a very rare form of typical OC. This defect is associated with dental anomalies such as hypodontia, microdontia, and ectopia as well as with dysmorphology of the facial complex outside the cleft area, including mild hypertelorism, hypoplasia of nasal bones and antheroposterior maxillary deficiency. Furthermore, aplasia of the frontal sinuses and the sacral spina bifida occulta have been observed. These findings are consistent with clinical data indicating strong correlation between development of a major defect and multiple minor anomalies. The results of the study also suggest that there was tolerant attitude towards the facial deformities among the ancient Altai pastoralists. Copyright © 2016 John Wiley & Sons, Ltd.

The specifics of adhesion function of endothelium in various clinical variants of primary mitral valve prolapse

Aim . To assess the condition of adhesion function of endothelium in various clinical variants of primary mitral valve prolapse (MVP). Material and methods. Totally, 91 patient studied with primary MVP at the age 21 (19-24) y. First grade mitral regurgitation was found in 45,1% and II — in 54,9% patients. MVP was solitary variant (6,6%) and comorbid with 1-3 minor anomalies of the heart (93,4%). Doppler-echocardiography was done on Vivid07 equipment (Israel). The grade of systemic involvement of connective tissue was 2 (1,5-4,0) points. Controls were 10 healthy persons, matched by age, sex, smoking, body mass index. By the immune enzyme method we checked plasmatic concentrations of L-, E-, Р-selectins, ICAM-1, VCAM-1, PECAM-1 (Bender MedSystems GmbH, Austria). Findings are presented as mediana (25-75 percentiles). Results . In MVP patients the levels of Е-selectin — 43,0 (33,7-54,8) ng/ mL, ICAM-1 — 669,9 (546,4-883,3) ng/mL and VCAM-1 — 925,0 (707,5- 1215,0) ng/mL, were significantly higher, and the level of РЕСАМ-1 — 49,8 (40,4-63,2) ng/mL, in opposite, lower than in control group. L- and P-selectins levels in MVP group were measured as relevant to controls values (p>0,05). In regurgitation cases of II degree, the level of E-selectin and ICAM-1 were maximal (p<0,05). Values of VCAM-1 in MVP patients independently from degree of regurgitation were significantly higher than controls values. There was moderate direst relation of the quantity of minor heart anomalies and level of ICAM-1 (rs=+0,30, р<0,05). In MVP group with increased E-selectin significantly higher was aorta diameter at the level of Valsalva sinuses — 2,5 (2,3-2,7) cm, than in PMV without increased E-selectin level — 2,3 (2,2-2,5) cm (р<0,05). Conclusion . In patients with primary MVP there is an increase of circulating concentrations of E-selectin, ICAM-1, VCAM-1, that represents the level of adhesion, and witnesses about subclinical endothelial dysfunction. For screening evaluation of severity of adhesion disorders of endothelium in MVP it is important to take into account its hemodynamic significance, multiple minor heart anomalies and data on aorta diameter on the level of Valsalva sinuses.

Rare interstitial deletion of chromosome 2p11.2p12. Report of a new patient with developmental delay and unusual clinical features

De novo interstitial deletions of the short arm of chromosome 2 are rare chromosomal abnormalities. Patients showing these kind of microdeletions have developmental delay/intellectual disability, minor facial anomalies including high forehead, frontal bossing, broad nasal bridge, abnormal ears and congenital defects such as skeletal and genital malformations. We describe the second child of a healthy and non consanguineous couple presenting at birth multiple malformations and minor facial anomalies. Because of the clinical findings, an array CGH analysis was performed using Agilent 60K microarray oligonucleotide. The analysis detected a 9.3 Mb deletion on the short arm of chromosome 2 at band p11.2p12 spanning the bases 77,946,599-87,277,610. The five patients previously described display a minimal common deleted region which explains the clinical features shared by all of them, while their individual characteristics might be explained by the different sizes of the deletion. The common deleted region involves several genes (CTNNA2, LRRTM1, REEP1), highly expressed in the nervous system. The deletion found in this case overlaps with most of those reported in literature but our patient displays extra clinical signs such as bilateral choanal atresia and atrial septal defect. It was impossible to find any direct correlation between the genes involved in the deletion and the choanal atresia and the heart defect. The question remains open as to whether these clinical features are a consequence of the deletion or are due to a second pathogenic event. Our case emphasizes the difficulties to find a close correlation between a large deletion and a well defined clinical picture. As only five patients with 2p11.2p12 deletions, reported in the literature are characterized by array CGH, further reports will be necessary to well define a clinical phenotype related to the 2p11.2p12 microdeletion.

The clinical geneticist and the evaluation of failure to thrive versus failure to feed.

Common clinical genetic referrals for the pediatric patient include a single major or multiple minor anomalies, dysmorphic features, especially when accompanied by developmental delay or intellectual disability, and failure to thrive (FTT). This review provides pediatric definitions of FTT and the genetic differential for FTT, which includes chromosomal disorders, microdeletion/duplication syndromes, uniparental disomy/methylation disorder, disorders of DNA repair, teratogens, metabolic syndromes, and skeletal dysplasias. Three clinical genetics cases highlight challenges in deciphering the cause of FTT. The review concludes with a ten-step approach that might improve diagnostic ability in differentiating FTT cases (those with genetic or other metabolic causes) from "failure to feed," in other words FTT as the direct result of neglect and/or child abuse.

Clinical presentation and survival in a population-based cohort of infants with gastroschisis in Utah, 1997-2011.

Typically gastroschisis is considered an isolated birth defect; however, other major malformations are reported to occur in 5-35% of cases depending on inclusion criteria. This study evaluated the associated malformations, small for gestational age, and survival among a clinically well-characterized population-based gastroschisis cohort, delivered from 1997-2011. We used data from Utah's statewide population-based surveillance system, which monitors major structural birth defects among all pregnancy outcomes (i.e., live births, stillbirths, pregnancy terminations, and miscarriages). Of the initial 387 gastroschisis cases, we excluded 51 (13.2%) for the following reasons: inadequately described or macerated fetuses, part of a specific malformation complex or sequence (limb-body wall complex, amniotic band sequence, or a severe form of abdominoschisis), leaving a study sample of 336 clinically confirmed cases. Gastroschisis was isolated non-syndromic in 284 cases (84.5%). One case was syndromic (trisomy 16; 0.3%) and the remaining 51 (15.2%) were classified as multiple: one unrelated major malformation (27; 52.9%); two or more unrelated major malformation or one major with multiple minor anomalies or mild malformations (6; 11.8%); ≥ one distinctive minor anomaly or mild malformation (13; 25.5%); amyoplasia (5; 1.5%). Of the liveborn infants, 63.3% were preterm (delivered at <37 weeks of gestation) and 21.8% were small for gestational age (SGA). SGA was more common in males (38.8%) than females (16%) (P = 0.008). Overall first year survival was high (95.6%); however, preterm infants with congenital intestinal atresia had the highest mortality (13.8%). The high proportion of isolated cases (84.5%) in gastroschisis is similar to that observed in many other phenotypes and not unique to gastroschisis. Because one in every six infants with gastroschisis had a major unrelated malformation, additional malformations should be sought in every newborn with gastroschisis. Infant mortality was low overall but still a significant concern in affected preterm infants with associated congenital intestinal atresia.

Minor anomalies in stillborn and second trimester miscarried fetuses.

In 1964, the landmark paper of Marden, Smith, and McDonald established that multiple minor anomalies in newborn infants are associated with an increased risk for major malformations. There were until now no comparable studies in stillbirths. The Wisconsin Stillbirth Service Program (WiSSP) has data regarding nearly 3,000 stillbirths and second trimester losses that have been analyzed for major anomalies and cause of death. One dysmorphologist retrospectively reviewed all 2,397 with usable photographs. Minor anomalies were identified in 1,413 (59%) with 575 of these (41%) having at least one major anomaly. Probability of a major anomaly increased from 7% with no minor anomalies to 15%, 36%, 67%, and 89% with 1, 2, 3, and >33 minor anomalies, respectively. Frequency of minor anomalies was less with lower resolution photographs, but did not show significant differences with maceration or gestational age. The most frequent minor anomalies were infraorbital creases/folds, lowset/posteriorly angulated ears, nuchal edema, flat face, equinovarus foot, camptodactyly, upslanted palpebral fissures, ear antihelix abnormalities (combined), micrognathia/retrognathia, and single transverse palmar crease. Except for infraorbital creases/folds each of these minor anomalies was strongly correlated with major anomalies (P < 0.0001). Infraorbital folds were the only anomaly which increased with placental cause of death, and reanalysis with placental causes excluded showed the expected relationship to major anomalies, suggesting that infraorbital folds may be markers for oligohydramnios due to various causes including placental hypoperfusion. Minor anomalies correlate with presence of major anomalies in stillborn fetuses, regardless of gestational age and maceration, and can provide information to guide decisions regarding laboratory testing and other evaluations.

A rare case of os odontoideum from an Early Intermediate period tomb at the Huacas de Moche, Peru

Os odontoideum is an uncommon vertebral anomaly where there is a smoothly corticated ossicle independent from a shortened odontoid peg. An example of os odontoideum was observed in an Early Intermediate period skeleton excavated from the Huacas de Moche (Moche IV, AD 400–700), Peru. The affected individual is a middle adult male who presents additional minor developmental anomalies of the axial skeleton. This individual was interred with a middle adult female who also has developmental anomalies of the axial skeleton, including block cervical vertebra (Klippel–Feil). Os odontoideum is infrequently reported in the medical literature and there continues to be debate about whether it is acquired or congenital. Unlike clinical cases, archaeological cases present an opportunity to examine the entirety of the skeleton. In the present case, there does not appear to be macroscopic or radiographic evidence for a healed fracture, and since the individual has multiple minor axial developmental anomalies, a congenital etiology is plausible. This case is the first to be described from the archaeological context of South America and one of few paleopathological examples worldwide.

Stillbirth risk among fetuses with ultrasound-detected isolated congenital anomalies.

To estimate the risk of stillbirth among pregnancies complicated by a major isolated congenital anomaly detected by antenatal ultrasonography and the influence of incidental growth restriction. A retrospective cohort study of all consecutive singleton pregnancies undergoing routine anatomic survey between 1990 and 2009 was performed. Stillbirth rates among fetuses with an ultrasound-detected isolated major congenital anomaly were compared with fetuses without major anomalies. Stillbirth rates were calculated per 1,000 ongoing pregnancies. Exclusion criteria included delivery before 24 weeks of gestation, multiple fetal anomalies, minor anomalies, and chromosomal abnormalities. Analyses were stratified by gestational age at delivery (before 32 weeks compared with 32 weeks of gestation or after) and birth weight less than the 10th percentile. We adjusted for confounders using logistic regression. Among 65,308 singleton pregnancies delivered at 24 weeks of gestation or after, 873 pregnancies with an isolated major congenital anomaly (1.3%) were identified. The overall stillbirth rate among fetuses with a major anomaly was 55 per 1,000 compared with 4 per 1,000 in nonanomalous fetuses (adjusted odds ratio [OR] 15.17, 95% confidence interval [CI] 11.03-20.86). Stillbirth risk in anomalous fetuses was similar before 32 weeks of gestation (26/1,000) and 32 weeks of gestation or after (31/1,000). Among growth-restricted fetuses, the stillbirth rate increased among anomalous (127/1,000) and nonanomalous fetuses (18/1,000), and congenital anomalies remained associated with higher rates of stillbirth (adjusted OR 8.20, 95% CI 5.27-12.74). The stillbirth rate is increased in anomalous fetuses regardless of incidental growth restriction. These risks can assist practitioners in designing care plans for anomalous fetuses who have elevated and competing risks of stillbirth and neonatal death. II.

Distribution of congenital anomalies in a neonatal intensive care unit in Turkey

Background: Congenital anomalies are one of the important reasons of mortality and morbidity in newborns. The aim of this study is to determine the incidence, distribution and the mortality of the congenital anomalies in a single neonatal intensive care unit (NICU) from Turkey.Method: A retrospective analysis was performed between 2005 and 2012 in NICU using a computerized database. Variables including the type of anomaly, antenatal and postnatal history, gestational age, birth weight, consanguinity and other demographic, clinical and related laboratory variables were extracted from the computerized database using ICD-10 codes. Congenital anomalies were classified according to involved organ systems and also classified as single and multiple anomalies.Results: A total of 1024 newborns with congenital anomaly (CA) (13.7%) were identified among the 7450 hospitalized newborns in NICU. The most affected system was the cardiovascular system (68.8%). Most of the anomalies (67.1%) were single anomalies. Of all, 59.4% had single major, 7.7% had single minor, 9% had single major plus single minor, 18.4% had multiple major and 2% had multiple minor anomalies. On the other hand, 96.3, 1.9, 0.1 and 1.7% of the newborns had malformation, deformation, disruption and dysplasia, respectively. Chromosomal analysis was only performed 24.8% of the newborns with CA and among them, 65.3% of these were in normal limits. The most frequently detected chromosomal abnormality was trisomy 21. Overall, mortality rate was 15.5% among the newborns with CA.Conclusion: In conclusion, the most common and mortal CA was cardio-vascular malformations in our hospital. The overall prevalence of cardio-vascular malformations among the newborn was higher than previously reported studies in Turkey. Further, studies with larger sample size are needed to determine CA in Turkey.

Congenital heart defects and major structural noncardiac anomalies in Alberta, Canada, 1995–2002

Although the majority of congenital heart defects (CHDs) occur in isolation, a significant number occur with noncardiac anomalies. This study determined the proportion of noncardiac anomalies among CHD cases in Alberta. Records of infants and children born in Alberta between January 1, 1995, to December 31, 2002, were searched using multiple sources of ascertainment in addition to the Alberta Congenital Anomalies Surveillance System (ACASS) (Alberta Health and Wellness, 2012). Each case was assigned to one CHD category and was further categorized into one of the following groups: isolated CHD, syndromes, chromosomal, associations and sequences, teratogens, Mendelian, neoplasia, heterotaxy, multiple minor anomalies, and multiple major anomalies. Of all 3751 CHD cases (prevalence 12.42/1000 total births: confidence interval, 12.03-12.83), 75% were isolated, 10% had a chromosomal etiology, and 9% had multiple major anomalies. All other categories accounted for <2% each. The most commonly associated major noncardiac anomalies were musculoskeletal (MSK) (24%) followed by anomalies of the urinary tract (14%), gastrointestinal system (GI) (11%), and central nervous system (CNS) (11%). This is both a population-based and clinical study using a classification scheme that could help to determine possible etiologic factors contributing to CHD. By eliminating known etiologies such as chromosomal and single gene, future studies can focus on the remainder to evaluate possible preventive measures. The most commonly associated major noncardiac anomalies involve the MSK system, followed by the urinary, GI, and CNS systems.

A systematic analysis of small supernumerary marker chromosomes using array CGH exposes unexpected complexity

A small supernumerary marker chromosome is often seen in patients with developmental disorders. Prior to array-based comparative genomic hybridization markers were rarely genotyped end to end. In this study, a valid genotype-to-phenotype correlation was possible because the supernumerary marker chromosomes were fully characterized by array-based comparative genomic hybridization in a genome-wide analysis. Ten consecutive de novo small supernumerary marker chromosome cases were systematically genotyped using G-banding, C-banding, AgNOR staining, whole-genome array-based comparative genomic hybridization, and fluorescence in situ hybridization. Among 10 small supernumerary marker chromosome cases studied, 4 (40%) were not identified by array-based comparative genomic hybridization because of low-level mosaicism or because they lacked euchromatin. One case (10%) was a simple pericentromeric marker extending from 5p13.3 to 5q11.2. Five (50%) markers showed unexpected complexity. Two cases had markers that were derivative acrocentric (AgNOR+) chromosomes with the euchromatin from chromosomes 18p or 19p. Each of the other three cases with complex markers had unusual characteristics including a marker from noncontiguous segments of chromosome 19q, a highly complex rearrangement involving a chromosome 20 homolog as well as the small supernumerary marker chromosome, and a mosaic duplication of a proximal 8p marker. Small supernumerary marker chromosomes are frequently complex on the basis of our small sample. Whole-genome array-based comparative genomic hybridization characterization of the small supernumerary marker chromosome provided informed genetic counseling.

Dextrocardia, atrial septal defect, severe developmental delay, facial anomalies, and supernumerary ribs in a child with a complex unbalanced 8;22 translocation including partial 8p duplication

We report on a child with dextrocardia, atrial septal defect (ASD), severe developmental delay, hypotonia, 13 pairs of ribs, left preauricular choristoma, hirsutism, and craniofacial abnormalities. Prenatal cytogenetic evaluation showed karyotype 46,XY,?dup(8p)ish del(8)pter. Postnatal array CGH demonstrated a 6.8 Mb terminal deletion at 8p23.3-p23, an interstitial 31.1 Mb duplication within 8p23.1-p11, and a terminal duplication of 0.24 Mb at 22q13.33, refining the karyotype to 46,XY,der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1).ish der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1) (D8S504-,MS607 + ,ARSA + ,D8Z1 + , RP115713 + +). Previous reports of distal 8p deletion, 8p duplication, and distal 22q duplication have shown similar manifestations, including congenital heart disease, intellectual impairment, and multiple minor anomalies. We correlate the patient's clinical findings with these particular areas of copy number. This case study supports the use of aCGH to identify subtle chromosomal rearrangement in infants with cardiac malformation as their most significant or only apparent birth defect. Additionally, it illustrates why aCGH is essential in the description of chromosome rearrangements, even those seemingly visible via routine karyotype. This method shows that there is often greater complexity submicroscopically, essential to an adequate understanding of a patient's genotype and phenotype.

Inv dup del(4)(:p13 → p16.3::p16.3 → qter) in a girl without typical manifestations of Wolf–Hirschhorn syndrome

We report on a 4-year-old girl who presented with microcephaly, multiple minor anomalies of face and limbs, congenital heart defect, hypotonia, neuropsychomotor delay, deafness and seizures. A GTG-banded karyotype identified an additional fragment of unknown origin on the terminal region of 4p. Parental karyotypes were normal. FISH analysis using a whole chromosome paint probe for chromosome 4 and subtelomere probes showed a signal on the entire add (4) chromosome and loss of the 4p subtelomere region, respectively. Additional analysis using microsatellite markers for chromosome 4 and whole-genome array comparative genomic hybridization (array-CGH) identified a duplication of the region 4p13 --> 4p16.3. Her karyotype was thus interpreted as an inverted duplication with terminal deletion of 4p: 46,XX,der(4)(:p13 --> p16.3::p16.3 --> qter). The clinical features of our patient differed from those typically observed in Wolf-Hirschhorn syndrome and were more compatible with duplication 4(p14 --> p16.3), with preservation of the WHS critical region.

S214: The Evaluation and Management of Medically Acquired Dentofacial Deformities

Advances in medical technology have allowed many young patients with often debilitating medical conditions to lead long productive lives. However, the effects that some diseases have on facial growth may result in significant functional deficits created by developmental dentofacial deformities. The probability that the oral surgeon involved in the care of dentofacial deformities will come across this patient population is significant. Recognition of multiple minor anomalies of the face and body can give a clue as to the possibility of major organ anomalies.

22q13.3 deletion syndrome: A recognizable malformation syndrome associated with marked speech and language delay

The 22q13.3 deletion syndrome is a recognizable malformation syndrome associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic facies. The prevalence of this disorder is unknown, but it is likely under-diagnosed. Age at diagnosis has varied widely, from cases diagnosed prenatally to 46 years. Males and females are equally affected. The distal 22q deletion can be detected occasionally by routine or high resolution chromosome analysis; however, the majority of cases are detected by FISH analysis, associated with deletion of the ARSA (control) probe when performing a FISH analysis for the velocardiofacial syndrome (del 22q11.2). The 22q13.3 deletion syndrome can accompany a simple chromosome deletion, an unbalanced translocation, or a ring chromosome. Primary care physicians, in addition to numerous specialists, play an important role in caring for patients with this disorder. Although the dysmorphic features observed in this condition are nonspecific, it is an important consideration in the differential diagnosis of children with developmental delay, hypotonia, marked speech and language disability, autistic-like features, multiple minor anomalies, and normal growth and head circumference.

Chromosome 5q subtelomeric deletion syndrome

The pure 3.5 Mb subtelomeric deletion syndrome is very rare but causes a recognizable phenotype characterized by prenatal lymphedema with increased nuchal translucency, pronounced muscular hypotonia in infancy, borderline intelligence, postnatal short stature with delayed bone age due to growth hormone deficiency, and multiple minor anomalies including mildly bell-shaped chest, minor congenital heart defects, and a distinct facial gestalt. Terminal deletions including the adjacent approximately 2 Mb NSD1-locus show a compound phenotype with overlap to Sotos syndrome. Larger terminal deletions including also chromosomal bands 5q35.1 and 5q35.2 cause a more severe phenotype with normal body length, significant congenital heart defect, microcephaly, profound developmental retardation or early death due to respiratory failure. Heart defects in the latter are explained by haploinsufficiency of the NKX2.5 gene at 5q35.1. The deletion breakpoint of the 3.5 Mb subtelomeric microdeletion maps to a low copy repeat which is identical to the distal copy of two highly similar regions flanking the recurrent interstitial NSD1 microdeletion. As meiotic mispairing between these low copy repeats seem to be much more likely than a terminal aberration, these neighborhood may prevent occurrence of the subtelomeric deletion syndrome, which could explain the rareness of the latter.

S215: The Evaluation and Management of Medically Acquired Dentofacial Deformities

Advances in medical technology have allowed many young patients with often debilitating medical conditions to lead long productive lives. However, the effects that some diseases have on facial growth may result in significant functional deficits created by developmental dentofacial deformities. The probability that the oral surgeon involved in the care of dentofacial deformities will come across this patient population is significant. Recognition of multiple minor anomalies of the face and body can give a clue as to the possibility of major organ anomalies. One must be able to recognize the impact of the medical conditions present on the ability to have a safe orthognathic surgical event. If one utilizes these diagnostic tools to learn about their patients, then corrective jaw surgery in this patient population is a predictable treatment modality. Correction of these functional deficits created by misaligned skeletal bases will have significant impact on the patient’s functional rehabilitation and quality of life. The medical conditions, such as chronic anemias, radiation induced micrognathia, rheumatoid arthritis, myotonic conditions, and ectodermal dysplasias often lead to the development of significant dentofacial deformities. The impact of these medical conditions on the surgical treatment plan as well as perioperative anesthetic management, and postoperative care will be reviewed. Evaluation and Management of Medically Acquired Dentofacial Deformities I. Review of Medical Conditions that cause Dentofacial Deformities Chronic Anemias Myotonias Ectodermal Dysplasias Radiation induced micrognathia Rheumatoid Arthritis Treatment planning for corrective jaw surgery Orthodontic considerations Osteotomy design Anesthetic Considerations Long-term issues Stability of correction Need for prosthetic management and timing References

De novo pure 12q22q24.33 duplication: First report of a case with mental retardation, ADHD, and Dandy‐Walker malformation

We present a patient with a de novo 12q nonmosaic pure duplication characterized by multiple minor anomalies and Dandy-Walker malformation. A neurological and behavioral assessment revealed psychomotor retardation and attention deficit/hyperactivity disorder (ADHD), with neurobehavioral abnormalities (auto- and heteroaggressive behavior). Fluoxetine therapy in this case markedly improved the neurobehavioral profile, with a decreased level of aggression. To define the extension of the duplicated region, we performed FISH analyses by using YAC probes. The analyses revealed a tandem duplication of the 12q22q24.33 region, with the proximal breakpoint located between 96.5 and 97.6 cM and the distal one between 154 and 161 cM. This is the first case of pure de novo duplication involving the 12q22q24.33 region. To better define the clinical phenotype associated with 12q partial duplication, we compared our case with the four patients with similar pure duplications previously described.

Imagerie par résonance magnétique du retard mental non spécifique

Mental retardation is considered idiopathic or not otherwise specified when no etiological diagnosis can be identified in spite of comprehensive history, physical examination and metabolic or genetic investigations. In such cases, brain MRI is indicated for patients with abnormal head size or shape, craniofacial malformation, somatic anomalies, neurocutaneous findings, seizures, focal neurological findings or behavioral and/or developmental problems. Brain anomalies are now considered a main category for the etiology of mental retardation. MRI evaluation should include axial images of the entire brain, sagittal images through the midline structures, and coronal images of the posterior fossa or entire brain. MRI allows detection of major and or minor cerebral anomalies or malformations, sometimes multiple. In the literature, the most frequently involved structures include: 1/ corpus callosum (hypoplasia, short corpus callosum and verticalized splenium), 2/ septum pellucidum (cavum septum pellucidum or cavum vergae), 3/ ventricles (ventriculomegaly), 4/ cerebral cortex (cortical dysplasia), 5/ cerebellum (hypoplasia), and 6/ extra-axial CSF spaces (enlargement). In our patient population, dysplasia involving the cerebellum and vermis have been identified, a finding that has not yet been described in the literature. MRI allows detection of multiple minor morphological anomalies. Most have classically been considered as normal variants but they may in fact be markers of cerebral dysgenesis and are currently the only anomaly detected in the work-up of patients with mental retardation. Their role in the pathogenesis of mental retardation is under evaluation.

Opitz “C” trigonocephaly‐like syndrome in a patient with terminal deletion of 2p and partial duplication of 17q

A boy with trigonocephaly, cleft palate, multiple minor anomalies, flexion deformities of elbows, cryptorchidism, and severe muscular hypotonia had an unbalanced karyotype with duplication of the distal 17q and deletion of the tip of 2p. This was derived from a reciprocal translocation in the father, 46,XY,t(2;17)(p25;q24). The propositus had some findings observed in patients with distal dup(17q), while trigonocephaly not found in these patients may be associated with the terminal deletion of 2p including the locus of SOX11 gene. It is proposed that the major clinical findings of this patient are consistent with the phenotype characteristic of the Opitz "C" trigonocephaly syndrome.