Clinodactyly Of Fingers Research Articles

Novel variants in the SOX11 gene: clinical description of seven new patients.

Pathogenic SOX11 variants have been associated with intellectual developmental disorder with microcephaly, and with or without ocular malformations or hypogonadotropic hypogonadism (HH) (IDDMOH, OMIM # 615866). In this article, we report seven new patients with de novo SOX11 variants. Five of the variants are missense, one nonsense, and one whole-gene deletion, most of them are novel variants. The main clinical features included neurodevelopmental delay (7/7) and intellectual disability (5/7), autism/attention deficit hyperactivity disorder (5/7), microcephaly (4/7), short stature (4/7), hypotonia (4/7), and clinodactyly of the 5th fingers (5/7). HH was confirmed in two female patients with primary amenorrhea, nonvisualized/prepubertal size of the uterus, and nonvisualized ovaries. Two of the male patients presented with micropenis, two had cryptorchidism, and one had decreased testicular size, which are suggestive findings of HH. This article contributes to the clinical characterization of patients with SOX11 variants and supports the role of this gene in HH.

The Distribution of Curvature of Little Finger (Clinodactyly) among the Idoma People of Benue State, Nigeria

Background: A bilateral malformation known as Clinodactyly, or curvature of the little finger in the radio-ulnar plane, causes the finger to be stunted and curved, or inclined, towards the ring finger. It is known to be a morphogenetic trait. Reports say that Clinodactyly seems to be passed on by a single autosomal dominant gene. There is paucity of information on curvature of the little finger in the Idoma tribe of Benue State, Nigeria; hence, this study was aimed at determining the distribution of curvature of the little finger in the study population. Materials and Methods: The study was descriptive and cross-sectional in design with 401 participants recruited randomly following a multi-staged sampling method. Results and Discussion: The most frequent socio-demographic characteristics were age category 33-47yrs with 213(53.1%), male gender with 223(55.6%), Tertiary education with 239(59.6%), Married/Co-habiting 220(54.9%), and Christianity 286(71.3%). The significant socio-demographic characteristic among participants were educational level (X2 =14.090, p=0.003) and marital status (X2 =10.901, p=0.05). The proportion of participants with a curved little finger was 18.9%. In the population a large portion of them had straight little finger. Conclusion(s): The proportion of participants with a curved little finger was 18.9%. In the population a large portion of them had straight little finger. The study showed that less than a third of the sampled population had a curved little finger and the remaining two-third a straight little finger. The ratio of curved to straight little finger was 1:4.

Novel frameshift variant in the PCNT gene associated with Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II and small kidneys

BackgroundMicrocephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II is an autosomal recessive condition encompassing a heterogeneous group of disorders characterized by symmetrical growth retardation leading to dwarfism, microcephaly, and a range of multiple medical complications including neurovascular diseases. Biallelic pathogenic variants in the pericentrin gene (PCNT) have been implicated in its pathogenesis.Case presentationWe performed whole-exome sequencing to ascertain the diagnosis of a 2 year and 6 months old boy who presented with severe failure to thrive, microcephaly, and facial gestalt suggestive of MOPD Type II which included features such as retrognathia, small ears, prominent nasal root with a large nose, microdontia, sparse scalp hair, bilateral fifth finger clinodactyly. He had a small ostium secundum atrial septal defect and bilaterally small kidneys. Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II was confirmed based on a pathogenic compound heterozygous frameshift variant in the PCNT gene c.5059_5060delAA | p. Asn1687fs (novel variant) and c.9535dup (p. Val3179fs). His parents were found to be heterozygous carriers for the variants.ConclusionWe report a novel frameshift variant in the PCNT gene and a previously unreported phenotype for Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II.

Sindrome de Silver-Russell: relato de caso

Objective: Silver-Russell syndrome (SRS) is a rare but well-recognized condition associated with classic phenotypic characteristics. This article aims to describe a patient with SRS, in order to help professionals in the diagnosis and adequate therapeutic management, since the early approach results in a better prognosis. METHODS: This is a case report of a male child, 1 year and 4 months old, admitted to an infirmary, who was diagnosed with SRS. Patient information was collected with the family during hospitalization. Analysis of medical records and literature review was also performed. RESULTS: A patient with chronic malnutrition, who had macrocranial physical examination, elongated facies, large ears with low implantation, occipital capillary rarefaction, micrognathia, hypospadias, 5th finger clinodactyly and delayed developmental milestones, received a diagnosis of SRS during hospitalization. Complementary exams ruled out pathologies of the gastrointestinal tract and in the speech-language evaluation, swallowing disorders were not detected. An enteral diet for nutritional recovery was initiated, but the patient maintained insufficient weight gain and an important food aversion, being the patient submitted to gastrostomy. On an outpatient return after hospital discharge, the patient remained low weight gain despite the use of hypercaloric formula and appropriate volume for his age. CONCLUSION: SRS leads to a wide spectrum of abnormal physical characteristics and functional abnormalities. Multidisciplinary monitoring and early, specific intervention are necessary for better management of this group of patients.

MON-054 First Report of Monozygotic Twins with Russell Silver Syndrome in China: Recombinant Growth Hormone Therapy and 3-Year Observation

BACKGROUND: Russell Silver syndrome (RSS) is a rare genetic condition that includes an important index of suspicion when a child presents with hemihyperthrophy. There are more than 400 cases described in the literature, but twin pairs with RSS have rarely been reported. Up to now only six monozygotic twin pairs have been described [1]. However, this has not been reported in east Asian population yet. Clinical Case: A 4 years and 9 months old monozygotic twin girl with a history of growth retardation was admitted to our hospital. The first impression of the patient was: poor growth, specific facial features, asymmetry of the lower and upper limbs for length and width. Detailed physical examination revealed a small triangular face with prominent forehead, micrognathia, lips with downturned corners, and fifth finger clinodactyly on bothhands. On admission into our hospital, the examination measured a weight of 9.0 kg (-4.9SD) and a length of 88.4 cm (-5.2SD). Anthropometrically she was classified as second grade malnutrition according to World Health Organization (WHO) charts. By contrast, her twin sister was physically and anthropometrically normal.Intrauterine growth retardation, postnatal growth retardation, normal head circumference and asymmetry of the body were the major criteria that made the clinical diagnosis of Russell-Silver syndrome. Confirmation of Russell-Silver syndrome was made based on clinical findings, birth history and results of molecular genetic testing showed hypomethylation of the paternal imprinting center 1 (IC1) of chromosome 11p15.5.Recombinant human growth hormone (rhGH) was administered by subcutaneous injection once daily, in the evening, at a dose of 0.05 mg/ kg/day. The check-up visits in the outpatient were held every three months, and the following issues were evaluated: response to treatment, tolerability, and laboratory test results, with particular emphasis on carbohydrate metabolism and bone age progression. Currently, after 28 months of rhGH treatment, the girl has grown 18 cm, reaching a body height of 106.5 cm (-3.2SD, ΔHt SDSCA: 2SD). Her current weight is 14.1 kg (-2.9SD, ΔWt SDSCA: 2SD). So far, no serious adverse events have been observed. Conclusion: This is the first case of monozygotic twin with Russell Silver syndrome reported in east Asian population. The possibility of rhGH treatment can be considered in cases of documented GH deficiency in patients with Russell Silver syndrome, under close endocrinic supervision.

Biallelic variants in KYNU cause a multisystemic syndrome with hand hyperphalangism.

Catel-Manzke syndrome is characterized by the combination of Pierre Robin sequence and radial deviation, shortening as well as clinodactyly of the index fingers, due to an accessory ossification center. Mutations in TGDS have been identified as one cause of Catel-Manzke syndrome, but cannot be found as causative in every patient with the clinical diagnosis. We performed a chromosome microarray and/or exome sequencing in three patients with hand hyperphalangism, heart defect, short stature, and mild to severe developmental delay, all of whom were initially given a clinical diagnosis of Catel-Manzke syndrome. In one patient, we detected a large deletion of exons 1-8 and the missense variant c.1282C > T (p.Arg428Trp) in KYNU (NM_003937.2), whereas homozygous missense variants in KYNU were found in the other two patients (c.989G > A (p.Arg330Gln) and c.326G > C (p.Trp109Ser)). Plasma and urine metabolomic analysis of two patients indicated a block along the tryptophan catabolic pathway and urine organic acid analysis showed excretion of xanthurenic acid. Biallelic loss-of-function mutations in KYNU were recently described as a cause of NAD deficiency with vertebral, cardiac, renal and limb defects; however, no hand hyperphalangism was described in those patients, and Catel-Manzke syndrome was not discussed as a differential diagnosis. In conclusion, we present unrelated patients identified with biallelic variants in KYNU leading to kynureninase deficiency and xanthurenic aciduria as a very likely cause of their hyperphalangism, heart defect, short stature, and developmental delay. We suggest performance of urine organic acid analysis in patients with suspected Catel-Manzke syndrome, particularly in those with cardiac or vertebral defects or without mutations in TGDS.

TGDS pathogenic variants cause Catel-Manzke syndrome without hyperphalangy.

Catel-Manzke syndrome, also known as micrognathia-digital-syndrome, is a rare autosomal recessive disorder characterized by the combination of the two cardinal features Pierre-Robin sequence and bilateral hyperphalangy leading to ulnar clinodactyly (ulnar curvature of the phalanges) and radial deviation (radial angulation at the metacarpophalangeal joint) of the index fingers. Individuals without one of these major hallmarks or with additional hand malformations have been described as atypical or Catel-Manzke-like syndrome. Biallelic TGDS pathogenic variants have thus far been detected in eight individuals with typical Catel-Manzke syndrome and in one fetus with additional features. Here we report on two individuals with TGDS pathogenic variants who presented with mild radial deviation and ulnar clinodactyly of the index fingers but without radiologic signs of hyperphalangy. Furthermore, both individuals have disproportionate short stature, a feature that has not yet been associated with Catel-Manzke syndrome. Our data broaden the phenotypic spectrum of TGDS-associated Catel-Manzke syndrome and expand the indication for diagnostic testing.

Molecular cytogenetic characterization of partial monosomy 2p and trisomy 16q in a newborn: A case report.

Trisomy 16q is a rare disorder with severe abnormalities, which always leads to early postnatal mortality. It usually results from a parental translocation, exhibiting 16q duplication associated with another chromosomal deletion. The present study reports on the clinical presentation and molecular cytogenetic results of a small-for-gestational-age infant, consisting of partial trisomy 16q21→qter and monosomy 2p25.3→pter. The proband presented with moderately low birthweight, small anterior fontanelles, prominent forehead, low hairline, telecanthus, flat nasal bridge, choanal atresia, clinodactyly of the fifth fingers, urogenital anomalies, congenital muscular torticollis and congenital laryngomalacia. The last two traits have not previously been reported in any trisomy 16q and monosomy 2p cases. The proband was trisomic for the 16q21→qter chromosomal region with the karyotype 46,XY,der(2)t(2;16)(p25;q21)pat. The chromosomal anomaly was the result of unbalanced segregation of a paternal balanced translocation, 46,XY,t(2;16)(p25;q21). In this case, molecular cytogenetic analysis had a critical role in delineating the proband's clinical phenotype. Although this patient had a 16q21→qter duplication and a 2p25.3→pter deletion, the latter may have had mild phenotypic effects when associated with trisomy 16q. The literature was also reviewed, focusing on cases with the same breakpoints, localizations and clinical features reported in recent years.

A novel frameshift variant in BHLHA9 underlies mesoaxial synostotic syndactyly associated with postaxial polydactyly

Mesoaxial synostotic syndactyly (MSSD) with phalangeal reduction is an uncommon congenital limb abnormality characterized by central osseous synostosis at a metacarpal level, mesoaxial reduction of the fingers, and preaxial cutaneous syndactyly in toes. In rare cases, the disease is also associated with fifth finger clinodactyly and postaxial polydactyly. It has autosomal recessive inheritance pattern caused by homozygous variants in the gene BHLHA9 mapped at chromosome 17p13.3.In the present study, a consanguineous family of Pakistani origin segregating MSSD in autosomal recessive form was characterized at clinical and genetic levels. Clinically, the diseased individuals have MSSD associated with clinodactyly and polydactyly. Homozygosity mapping followed by Sanger sequencing of BHLHA9 revealed a novel frameshift variant NM_001164405.1: c.409-409delC; p.(His137Thrfs*61) segregating with the disease phenotypes in the family.This is the second report providing evidence of association of polydactyly with MSSD caused by frameshift variant in the gene BHLHA9. The present molecular investigation will support genetic counselling of the local population carrying diseased variants.

Постнатальна діаґностика синдрому палістера-кілліана за допомогою інтерфазного fish-методу на клітинах букального епітелію

Aim. Diagnosis of Pallister-Killian syndrome. For the verification of the diagnosis of Pallister-Killian syndrome, children with multiple facial dysmorphia, muscular hypotonia, and retarded growth and development were examined. Material and Methods. The material for conducting cytogenetic examination were lymphocytes of the patients' peripheral blood, analyzed by metaphase plates according to standard methods, not less than 20 cells stained with the G-method. The material for the molecular cytogenetic method on the interphase nuclei (nuc-FISH) was buccal mucosa. The nuc-FISH method was conducted in accordance with the manufacturer's  instructions to the probe 12p13/21q22 LSI ETV6 (TEL)/RUNX1 (AML1) ES of Vysis, USA. To confirm the diagnosis, the dual color DNA-label of 12p13/21q22 LSI ETV6 (TEL) / RUNX1 (AML1) ES was used. 100 cells were analyzed, counting the number of signals in each cell. The result was considered positive if three and four green signals of the locus 12p13 shone in each nucleus. Results and Discussion. For three years, in the Specialized Medical Genetic Center, three cases of Pallister-Killian syndrome were observed in children with specific facial dysmorphia, muscular hypotonia, and severe retardation of physical and mental development. All cases were combined with the following phenotype: a flat neck; a prominent forehead; a flat and broad nasal root and a short nose with anteverted nostrils; macroglossia; micrognatia; large ears with thick protruding lobules; sparse anterior scalp hair in infancy; ocular hypertelorism; upslanting palpebral fissures with sparse eyebrows and eyelashes; a long philtrum with thin upper lip and distinct Cupid-bow shape; the fifth finger clinodactyly; the simian crease; a shortened hip bone. No seizures were observed. All children needed an examination of the sound specialist. Occasional abnormalities included the following: in the first case, there was central amaurosis and congenital deafness; the second patient presented with additional breast nipples (six in total); in the third case a congenital heart defect was observed. In all cases, the karyotype of peripheral blood lymphocytes was normal. The result of nuc-FISH of buccal mucosa cells revealed mosaicism signals of 12p13. In medical-genetic counseling of children with symptoms of chromosomal pathology, patients undergo cytogenetic examination according to classical tactics. Obtaining a normal karyotype usually complicates further diagnostics. Taking into account the etiology of Pallister-Killian syndrome, in order to diagnose it, we introduced the nuc-FISH technique on the buccal mucosa cells using a locus-specific probe 12p13. Thus, the diagnosis of Pallister-Killian syndrome in our center has been confirmed in three cases. Conclusions. The clinical presentation of the confirmed cases of Pallister-Killian syndrome corresponds with that described in literary sources. The nuc-FISH method on the buccal mucosa is recommended to be used as a rapid and non-invasive method for diagnosis of Pallister-Killian syndrome.

A boy with developmental delay and mosaic supernumerary inv dup(5)(p15.33p15.1) leading to distal 5p tetrasomy \u2013 case report and review of the literature

BackgroundWith only 11 patients reported, 5p tetrasomy belongs to rare postnatal findings. Most cases are due to small supernumerary marker chromosomes (sSMCs) or isochromosomes. The patients share common but unspecific symptoms such as developmental delay, seizures, ventriculomegaly, hypotonia, and fifth finger clinodactyly. Simple interstitial duplications leading to trisomies of parts of 5p are much more frequent and better described. Duplications encompassing 5p13.2 cause a defined syndrome with macrocephaly, distinct facial phenotype, heart defects, talipes equinovarus, feeding difficulties, respiratory distress and anomalies of the central nervous system, developmental delay and hypotonia.Case presentationWe present a boy with dysmorphic features, developmental delay, intellectual disability and congenital anomalies, and a mosaic sSMC inv dup(5)(p15.33p15.1). He is the fourth and the oldest reported patient with distal 5p tetrasomy. His level of mosaicism was significantly different in lymphocytes (13.2%) and buccal cells (64.7%). The amplification in our patient is smaller than that in the three previously published patients but the only phenotype difference is the absence of seizures in our patient.ConclusionsOur observations indicate that for the assessment of prognosis, especially with respect to intellectual functioning, the level of mosaicism could be more important than the extent of amplification and the number of extra copies. Evaluation of the phenotypical effect of rare chromosomal aberrations is challenging and each additional case is valuable for refinement of the genotype-phenotype correlation. Moreover, our patient demonstrates that if the phenotype is severe and if the level of sSMC mosaicism is low in lymphocytes, other tissues should be tested.

A novel GJA1 mutation in oculodentodigital dysplasia with extensive loss of enamel

To characterize clinical features and identify genetic causes of a patient with oculodentodigital dysplasia (ODDD). Clinical, dental, radiological features were obtained. DNA was collected from an affected Thai family. Whole-exome sequencing was employed to identify the disease-causing mutation causing ODDD. The presence of the identified variant was confirmed by Sanger sequencing. The proband suffered with extensive enamel hypoplasia, polysyndactyly and clinodactyly of the 3rd-5th fingers, microphthalmia, and unique facial characteristics of ODDD. Mutation analysis revealed a novel missense mutation, c. 31C>A, p.L11I, in the GJA1 gene which encodes gap junction channel protein connexin 43. Bioinformatics and structural modeling suggested the mutation to be pathogenic. The parents did not harbor the mutation. This study identified a novel de novo mutation in the GJA1 gene associated with severe tooth defects. These results expand the mutation spectrum and understanding of pathologic dental phenotypes related to ODDD.

Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication.

Segmental Hemihyperplasia-Related Macrodactyly with Congenital Renal Agenesis: A Hand Surgeon's Point of View.

Segmental Hemihyperplasia-Related Macrodactyly with Congenital Renal Agenesis: A Hand Surgeon's Point of View.

Terminal Gain of 12p13.33 and Terminal Loss of 9p24.3, Detected in a Child with Developmental Delay and Growth Issues and Due to a Maternal Unbalanced Rearrangement Between 12p and 9p

Down syndrome (DS) is the most common genetic cause of intellectual disability and is most commonly caused by complete trisomy of chromosome 21. Correlations between specific critical regions of chromosome 21 and key DS clinical features are incompletely characterized. Ectrodactyly is not associated with DS. We report a 4-year-old Guatemalan boy with developmental delay, referred to Genetics for evaluation of complex bilateral syndactyly and ectrodactyly. Following surgery, ulnar deviation of index fingers, radial deviation of middle fingers, and fifth finger clinodactyly were present bilaterally, together with variable hypoplasia of middle and terminal phalanges of the index, middle, and ring fingers. His head was small (5 centile), with bitemporal prominence and plagiocephaly. He had upslanting palpebral fissures, protruding ears, flattened midfacial appearance, and bilateral genu varus; no syndactyly or ectrodactyly was observed in the feet. Typical DS features not seen include tongue protrusion, single palmar creases, and hypotonia. DS was not initially suspected and FGFR2 sequencing was normal. Chromosomal SNP microarray (Illumina CytoSNP 850K) supported the mosaic karyotype: 47,XY,+21[3]/47,XY,+r(21)(p11.2q21.1) [3]/46,XY[6], and defined gene content of a ring chromosome 21 derived from 21p11.2-21q21.1, sparing the DS critical region. This is a highly atypical presentation of DS, and to our knowledge there are no reports implicating candidate genes or chromosomal regions on chromosome 21 in ectrodactyly, suggesting the complex mosaic karyotype as the likely cause. The presence of a trisomic cell line and absence of isodisomy of chromosome 21 support trisomy rescue as a plausible mechanism for mosaicism.

Complex Syndactyly and Atypical Ectrodactyly in a Child with a Mosaic Karyotype Involving Trisomy 21 and Partial Duplication of Chromosome 21

Down syndrome (DS) is the most common genetic cause of intellectual disability and is most commonly caused by complete trisomy of chromosome 21. Correlations between specific critical regions of chromosome 21 and key DS clinical features are incompletely characterized. Ectrodactyly is not associated with DS. We report a 4-year-old Guatemalan boy with developmental delay, referred to Genetics for evaluation of complex bilateral syndactyly and ectrodactyly. Following surgery, ulnar deviation of index fingers, radial deviation of middle fingers, and fifth finger clinodactyly were present bilaterally, together with variable hypoplasia of middle and terminal phalanges of the index, middle, and ring fingers. His head was small (5 centile), with bitemporal prominence and plagiocephaly. He had upslanting palpebral fissures, protruding ears, flattened midfacial appearance, and bilateral genu varus; no syndactyly or ectrodactyly was observed in the feet. Typical DS features not seen include tongue protrusion, single palmar creases, and hypotonia. DS was not initially suspected and FGFR2 sequencing was normal. Chromosomal SNP microarray (Illumina CytoSNP 850K) supported the mosaic karyotype: 47,XY,+21[3]/47,XY,+r(21)(p11.2q21.1) [3]/46,XY[6], and defined gene content of a ring chromosome 21 derived from 21p11.2-21q21.1, sparing the DS critical region. This is a highly atypical presentation of DS, and to our knowledge there are no reports implicating candidate genes or chromosomal regions on chromosome 21 in ectrodactyly, suggesting the complex mosaic karyotype as the likely cause. The presence of a trisomic cell line and absence of isodisomy of chromosome 21 support trisomy rescue as a plausible mechanism for mosaicism.

Clinical characteristics and imprinting analysis of Chinese Silver Russell Syndrome

Results There were 32 boys and 17 girls whose ages ranged from 3 m to 12 y. The main clinical characteristics of these SRS were: i) SGA and postnatal growth retardation (mean height standard deviation score (HT SDS) was 2.25; ii) Skeletal malformation including triangular-shaped face, small chin, irregular/crowded teeth, limbs asymmetry and fifth finger clinodactyly. Genetic analysis showed that ICR1 hypomethylation were 22/36 (61.1%) which were following: Ten had hypomethylation in chromosome 11p15 imprinting control region 1 (ICR1) of the paternal allele; seven had both hypomethylation in ICR1 and ICR2; five had hypomethylation in ICR1 and hypermethylation in ICR2. And UPD7 (mat) positive is 1/21 (4.8%). Six patients had been treated with growth hormone (GH) for 3 to 24 months. Growth rates ranged from 4 to 10.8 cm/year.

Outcomes of Opening Wedge Osteotomy to Correct Angular Deformity in Little Finger Clinodactyly

To evaluate the outcomes and complications in a series of children with clinodactyly treated with opening wedge osteotomy of the abnormal phalanx. We performed a retrospective review of all children with clinodactyly treated at our institution with opening wedge osteotomy of the abnormal middle phalanx between 2003 and 2013. Patients with concomitant pathology or prior surgery in the affected finger were excluded. Preoperative and postoperative clinical angle, radiographic angle, digital range of motion, and pain were compared and complications were recorded. We included 13 digits in 9 patients. All had greater than 20° of preoperative clinical angulation (mean, 36°). Mean age at time of surgery was 11 years; mean duration of follow-up was 25 months (range, 12-43 mo). All digits had significant improvement (mean, 32°) in clinical and radiographic angles after surgery. This improvement was maintained at final follow-up in 12 digits. Six patients had pain preoperatively and no patient had pain postoperatively. One digit had a recurrent deformity at final follow-up and 3 digits developed stiffness at the distal interphalangeal joint. Opening wedge osteotomy is an effective treatment for angulation in children with clinodactyly. We counsel families regarding the risk of distal interphalangeal joint stiffness. Therapeutic IV.

Refinement of genotype-phenotype correlation in 18 patients carrying a 1q24q25 deletion.

Interstitial deletion 1q24q25 is a rare rearrangement associated with intellectual disability, growth retardation, abnormal extremities and facial dysmorphism. In this study, we describe the largest series reported to date, including 18 patients (4M/14F) aged from 2 days to 67 years and comprising two familial cases. The patients presented with a characteristic phenotype including mild to moderate intellectual disability (100%), intrauterine (92%) and postnatal (94%) growth retardation, microcephaly (77%), short hands and feet (83%), brachydactyly (70%), fifth finger clinodactyly (78%) and facial dysmorphism with a bulbous nose (72%), abnormal ears (67%) and micrognathia (56%). Other findings were abnormal palate (50%), single transverse palmar crease (53%), renal (38%), cardiac (38%), and genital (23%) malformations. The deletions were characterized by chromosome microarray. They were of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3-q31.2 (chr1:160797550-192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1:164,501,003-167,022,133), associated with cardiac and renal anomalies, a distal one (chr1:178,514,910-181,269,712) and an intermediate 490 kb region (chr1:171970575-172460683, hg19), deleted in the most of the patients, and containing DNM3, MIR3120 and MIR214 that may play an important role in the phenotype. However, this genetic region seems complex with multiple regions giving rise to the same phenotype.

A 1.37-Mb 12p11.22–p11.21 deletion coincident with a 367-kb 22q11.2 duplication detected by array comparative genomic hybridization in an adolescent girl with autism and difficulty in self-care of menstruation

ObjectiveTo present an array comparative genomic hybridization (aCGH) characterization of a 12p11.22–p11.21 microdeletion and 22q11.2 microduplication in an adolescent girl with autism, mental retardation, facial dysmorphism, microcephaly, behavior problems, and an apparently balanced reciprocal translocation of t(8;12)(q24.3;p11.2). Materials and methodsA 13-year-old girl was referred to the hospital because of autism, mental retardation, and difficulty in the self-care of her menstruation. Cytogenetic analysis revealed an apparently balanced reciprocal translocation and a karyotype of 46,XX,t(8;12) (q24.3;p11.2)dn. The girl manifested microcephaly, hypertelorism, flat facial profile, prominent forehead, thick scalp hair, upslanting palpebral fissures, broad nasal bridge, bulbous nose, right simian crease, bilateral clinodactyly of the fifth fingers, bilateral pes cavus, learning difficulties, mental retardation, emotional instability, cognitive impairment, behavior problems, jumping-like gaits, and autistic spectrum disorder. aCGH was performed to evaluate genomic imbalance in this patient. ResultsaCGH analysis revealed a 1.37-Mb 12p11.22–p11.21 microdeletion or arr [hg 19] 12p11.22-p11.21 (30,645,008–32,014,774)×1 and a 367-kb 22q11.21 microduplication or arr [hg 19] 22q11.21 (18,657,470–19,024,306)×3. The 1.37-Mb 12p11.22–p11.21 microdeletion encompassed 26 genes including IPO8, CAPRIN2, and DDX11, and the 367-kb 22q11.21 microduplication encompassed 20 genes including USP18, DGCR6, PRODH, and DGCR2. ConclusionAn apparently balanced translocation may be in fact affected by concurrent deletion and duplication in two different chromosomal regions. Our presentation provides information on diagnostic phenotype of 12p11.22–p11.21 microdeletion and 22q11.2 microduplication.