Clinodactyly Of Fifth Fingers Research Articles

Proposed Phenotype for Females with a SETD5 Gene Variation: A Case Report

Background: SET domain containing 5 (SETD5) gene variants have been linked to developmental delays, craniofacial abnormalities, and intellectual disability (ID). Prior research examining the phenotypic presentation of individuals with SETD5 variations has been based largely on a male-dominated cohort and case studies. Evidence of a possible protective effect in females prompts the need for additional research on the neuropsychological presentation of females with a SETD5 variation. The current study aims to initiate this effort by discussing the neurocognitive profile of a right-handed 7-year-old Caucasian female with a diagnosed SETD5 variation. Methods and findings: The patient was referred for neuropsychological evaluation due to reported reading, writing, and fine motor difficulties. She presented with distinct dysmorphic features: head circumference <1st percentile, syndactyly of toes, clinodactyly of fifth fingers, and a long smooth philtrum with thin upper lip. Interpersonally, the patient was highly social. Cognitive testing revealed low average intelligence, with intact verbal/language functioning and impaired nonverbal/fluid reasoning abilities. Deficits were also observed in fine motor dexterity, visuomotor integration, attention, and broad academic achievement. The patient was ultimately referred for genetic testing, which revealed a de novo SETD5 frame shift variant resulting in a truncation of the gene copy near the end of the gene. Conclusion: This case study provides evidence for phenotypic differences between males and females with SETD5 gene variations. While males exhibit ID, females may present with significant deficits in nonverbal reasoning skills. Females may also display more fully developed social skills and a lack of repetitive stereotyped behaviors. Further research is warranted to clarify the unique presentation among females with SETD5 variations to better inform diagnosis and treatment planning.

Clinical report of 8 patients with 49,XXXXY syndrome: Delineation of the facial gestalt and depiction of the clinical spectrum

49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome. Cognitive impairment with expressive language deficits in combination with developmental and speech dyspraxia are cardinal symptoms. Testicular insufficiency becomes apparent during adolescence. Neurological, musculoskeletal, genital, orthodontic and immunological anomalies are common and a higher incidence of congenital malformations has been described. Here we show the evolving clinical and facial phenotype of eight boys and men with 49,XXXXY, demonstrating an increasingly perceptible distinct facial gestalt over time. In addition, almost all patients had muscular hypotonia, radioulnar synostosis, white matter anomalies, fifth-finger clinodactyly, recurrent respiratory infections in early childhood and teeth anomalies. IQ scores ranged between 40 and 70. Though many boys showed short stature at some point in early childhood, most outgrew it. As more long term data of boys and men with 49,XXXXY become available, parents of affected boys can be counseled more specifically as to the expected course and spectrum of this rare chromosomal disorder. Moreover, the multidisciplinary support can be optimized und unnecessary diagnostics avoided.

Systemic and maxillofacial characteristics of 11 Japanese children with Russell-Silver syndrome.

Russell-Silver syndrome (RSS) is a congenital anomaly characterized by intrauterine and postnatal growth retardation, typical facial features, fifth-finger clinodactyly, and skeletal asymmetry. Although data on intrauterine and postnatal growth retardation have been reported, there are few reports concerning the typical maxillofacial morphology in individuals with RSS. The aim of this study was to describe the details of this systemic condition and to characterize maxillofacial morphology based on cephalograms in 11 Japanese patients (age range, 3.9-12.0 years) with RSS. All 11 individuals had intrauterine and postnatal growth retardation. In addition, most showed mandibular retrognathia and relative macrocephaly. Lateral cephalogram measurements showed that mandibular retrognathia resulted from short mandibular body length, whereas the depth of the cranial base was close to normal. Although asymmetry of hand, foot, and limb length were present in most individuals, obvious facial asymmetry was not common. Differences between left and right skeletal and dental age were not observed, indicating that children with RSS might show asymmetry because of quantitative differences in skeletal growth rather than delayed growth rate. Our findings not only provide important information about the maxillofacial characteristics of RSS, but also help to clarify the association between these characteristics and genetics, which will add to the body of information on clinical symptoms.

Dilated cardiomyopathy in a 32-year-old woman with Russell–Silver syndrome

Russell-Silver Syndrome (RSS) is a genetically determined condition characterized by severe intrauterine and postnatal growth retardation; relative macrocephaly; a small, triangular face; and fifth-finger clinodactyly. The etiology of RSS involves epigenetic regulation through either uniparental disomy or genomic imprinting via DNA methylation. There has been no documented association between RSS and cardiomyopathy. We present an original case of a 32-year-old woman with RSS with dilated a cardiomyopathy who on cardiac biopsy showed occasional hypertrophic and atrophic myocytes with no evidence of inflammation, abnormal sarcomeres and disintegration of the Z bands on ultrastructural analysis, abnormal desmin, and normal C9 immunoreactivity. This case represents the first reported association between RSS and cardiomyopathy. Given the complex mechanisms of disease etiology in RSS, this novel case provides insights into the mechanism of progressive dilated cardiomyopathy in an older individual with RSS.

Analysis of clinical and genetic characteristics of 20 cases of children with Silver Russell syndrome

To improve the accuracy of the diagnosis of the disease on the basis of the clinical features and genetic characteristics of patients with Silver Russell syndrome (SRS). Patients diagnosed with SRS by Price criteria in 2006 to 2011 were reviewed for their clinical manifestations, physical signs, laboratory examinations and treatments. Twenty cases with SRS were 0.08-12.17 yr old. Fifteen were male and 5 were female. The clinical characteristics included more than 80% of cases had postnatal growth retardation 100% (20/20), craniofacial dysmorphism 100% (20/20), small for gestation age 95% (19/20), asymmetry and thinning of the face and/or limbs 90% (18/20), fifth finger clinodactyly 80% (16/20), BMI < -2 SDS 80% (16/20). Their height was obviously lagging behind in the bone age. HD SDS/average of bone retardation was 3.08. The two patients with the chief complaint of external genital abnormalities would have aggressive surgical treatment and they did not use the growth hormone (GH) treatment. Only six patients had used the GH treatment. GH treatment at a dose of 0.1 IU/(kg·d) used in 2 cases achieved a growth velocity (GV) 8 - 11 cm/yr but in another 2 cases < 5 cm/yr. In genetic study, 6 patients were found to have 11p15 low methylation, 1 had low and high methylation, 1 had duplication, no relation between clinical and methylation of 11p15 was found. There were great variations of clinical features in SRS characterized by small for gestation age and/or postnatal growth retardation, craniofacial dysmorphism, asymmetry of the face and/or limbs or ultrafine limbs, fifth finger clinodactyly. Severely low BMI was seen and height was obviously lagging behind in the bone age. The findings of laboratory tests and imaging of SRS were not specific. Some of SRS had 11p15 imprinting defects. The treatment of SRS is mainly symptomatic.

A de novo 4.4-Mb microdeletion in 2p24.3 → p24.2 in a girl with bilateral hearing impairment, microcephaly, digit abnormalities and Feingold syndrome

We report a 26-month-old girl with profound hearing impairment, microcephaly, psychomotor retardation, short palpebral fissures, hypertelorism, epicanthic folds, a broad nasal bridge, anteverted nostrils, large low-set ears, micrognathia, brachymesophalangy of the second and the fifth fingers, clinodactyly of bilateral fifth fingers and a wide interdigital space between the first and the second toes, carrying a 4.4-Mb de novo microdeletion of chromosome 2p24.3 → p24.2. This region contains the genes of FAM84A, NBAS, DDX1, MYCNOS and MYCN, of which haploinsufficiency or mutations of the MYCN gene is associated with Feingold syndrome. Brain magnetic resonance imaging revealed cochlear nerve hypoplasia and internal auditory canal stenosis. Temporal bone computed tomography showed abnormal dilation of bilateral vestibular and lateral semicircular canals. The present case provides evidence that haploinsufficiency of MYCN in 2p24.3 deletion in humans can cause structural and functional abnormalities of the inner ear.

Choanal Atresia Associated With Tracheoesophageal Fistula: The Spectrum of Carbimazole Embryopathy

This article focuses on the case of a newborn infant boy with bilateral choanal atresia, tracheoesophageal fistula, and bilateral fifth-finger clinodactyly. This infant had been exposed to carbimazole in utero during the treatment of maternal Graves disease. Teratogenic defects caused by carbimazole were recently recognized, and their phenotypes have been defined. Choanal atresia, esophageal atresia, athelia or hypothelia, developmental delay, hearing loss, and dysmorphic facial features have all been reported. To our knowledge, this is the first documented case of tracheoesophageal fistula without esophageal atresia (H type). Knowledge of the teratogenic potential of carbimazole is important when managing Graves disease in women of childbearing age.

Tissue‐limited mosaicism for monosomy 13

Karyotypic discordance between different tissues in an individual is uncommon. We report on a patient with multiple congenital anomalies and mosaicism for monosomy 13 limited to fibroblasts. Findings include microcephaly, agenesis of the corpus callosum, bilateral posterior colobomas, cataract and optic nerve dysplasia, patent foramen ovale, renal hypoplasia, hypospadias and unilateral inguinal hernia, unilateral hypoplasia of the lower limb, sparse and patchy hair, subtle pigmentary mosaicism, and global developmental delay. The lymphocyte karyotype was normal, whereas the fibroblast karyotype showed mosaicism for a del(13)(q11→ter). Review of the literature identified three previous reports of similar patients with multiple congenital anomalies, normal lymphocyte karyotype, and subsequent, diagnostic fibroblast karyotyping. Comparison of the previously reported patients with the patient reported here defines a common phenotype for tissue-limited mosaicism for monosomy 13 consisting of prenatal-onset growth deficiency; microcephaly; facial abnormalities including prominent nasal bridge, hypertelorism, ptosis, epicanthal folds, microphthalmia, coloboma, retinoblastoma, prominent maxilla, micrognathia, and low-set ears; limb abnormalities including small to absent thumbs, clinodactyly of fifth finger, fused metacarpal bones 4 and 5, talipes equinovarus, and short first toe; cardiac defect; renal anomalies; and genitalia abnormalities including hypospadias and cryptorchidism. In conclusion, this case further emphasizes that fibroblast karyotyping should be employed when the diagnosis remains unclear, especially in the presence of pigmentary mosaicism or segmental hypoplasia.

Dental management of oculodentodigital dysplasia: a case report

Oculodentodigital dysplasia is an extremely rare autosomal dominant pleiotropic disorder. The syndrome is characterized by abnormal facial features, central nervous system involvement, syndactyly and clinodactyly of fourth and fifth fingers, dry and lusterless hair, generalized enamel hypoplasia and odontodysplasia. Combination of odontodysplasia, poor oral hygiene, and parental neglect can lead to extensive destruction of tooth structure and the treatment options become limited. Early diagnosis with a proper treatment plan and meticulous oral hygiene program helps eliminate the necessity of multiple tooth extractions. This case report describes the comprehensive dental treatment aimed at rehabilitation of function and aesthetics of the dentition in an 8-year-old boy with oculodentodigital dysplasia.

Diagnosis of Russell-Silver Syndrome by the Combined Bisulfite Restriction Analysis–Denaturing High-Performance Liquid Chromatography Assay

Russell-Silver syndrome (RSS) is characterized by prenatal and postnatal growth retardation, triangular facies, and fifth-finger clinodactyly. Half of all patients with RSS have hypomethylation of the differentially methylated region of the H19 gene on chromosome 11p15.5. Hence, a quantitative methylation analysis of this region can be useful for the molecular diagnosis of RSS. However, conventional assays based on bisulfite clone sequencing are rather time and labor consuming and are not suitable for clinical use. In the present study, we investigated a possible method of quantitatively determining H19 hypomethylation in RSS patients using a combined bisulfite restriction analysis (COBRA)-denaturing high-performance liquid chromatography (DHPLC) assay; in this combined assay, polymerase chain reaction products amplified from the H19 differentially methylated region of bisulfite-treated genomic DNA were analyzed using a COBRA assay, which detects methylation-dependent sequence differences in the bisulfite-treated genomic DNA using a restriction enzyme analysis. We designed the assay so that a restriction enzyme (HinfI) would cut the methylated, but not the unmethylated, template. The molar ratio between the cut and uncut fragments was measured using DHPLC, and the construction of a calibration curve enabled the methylation index for the original genomic DNA to be estimated. An analysis of seven RSS patients using the COBRA-DHPLC assay demonstrated that three of the seven RSS patients had a low methylation index of around 10%. A comparison of the methylation indices obtained using COBRA-DHPLC and conventional bisulfite clone sequencing revealed an excellent intermethod agreement. In summary, we have developed a robust, rapid, and cost-effective COBRA-DHPLC-based screening system for RSS.

Absence of a Paternally Inherited FOXP2 Gene in Developmental Verbal Dyspraxia

Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few cases have been described. We characterize 13 patients with DVD--5 with hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome (SRS). Of these individuals with DVD, all 12 for whom parental DNA was available showed absence of a paternal copy of FOXP2. Five other individuals with deletions of paternally inherited FOXP2 but with incomplete clinical information or phenotypes too complex to properly assess are also described. Four of the patients with DVD also meet criteria for autism spectrum disorder. Individuals with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction, we show the maternally inherited FOXP2 to be comparatively underexpressed. Our results indicate that absence of paternal FOXP2 is the cause of DVD in patients with SRS with maternal UPD7. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.

Andersen syndrome: an association of periodic paralysis, cardiac arrhythmia and dysmorphic abnormalities

Andersen syndrome (AS) is a rare disease characterized by the presence of periodic paralysis (PP), cardiac arrhythmia and dysmorphic abnormalities. We report herein the first Brazilian patient presenting AS who also had obesity, obstructive sleep apnea (OSA) and daytime sleepiness. Clinical and genetic evaluation of six family members demonstrated that four had dysmorphic abnormalities but none had PP or cardiac arrhythmia. Sequencing of KCNJ2 revealed the R218W mutation in the index patient and her 6-year-old daughter, who presented dysmorphic abnormalities (micrognathia, clinodactyly of fourth and fifth fingers, short stature) and OSA. Three relatives had clinodactyly as the only manifestation but the R218W mutation was absent, suggesting that this characteristic may be influenced by another gene. OSA accompanied by dysmorphic features may be related to AS.

What Syndrome Is This?

Pediatric DermatologyVolume 22, Issue 4 p. 366-368 What Syndrome Is This? Susan B. Mallory M.D., Susan B. Mallory M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorBernice R. Krafchik M.B., Ch.B., F.R.C.P.C., Bernice R. Krafchik M.B., Ch.B., F.R.C.P.C. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorNawaf Al-Mutairi M.D., F.R.C.P., Corresponding Author Nawaf Al-Mutairi M.D., F.R.C.P. Department of Dermatology, Farwaniya Hospital, KuwaitAddress correspondence to Nawaf Al-Mutairi, M.D., F.R.C.P., P.O. Box: 280, Farwaniya, State of Kuwait, or e-mail: nalmut@usa.net.Search for more papers by this authorOsama Nour-Eldin M.D., Osama Nour-Eldin M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorArun Joshi M.D., Arun Joshi M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorAyman H. Hassanain M.D., Ayman H. Hassanain M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this author Susan B. Mallory M.D., Susan B. Mallory M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorBernice R. Krafchik M.B., Ch.B., F.R.C.P.C., Bernice R. Krafchik M.B., Ch.B., F.R.C.P.C. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorNawaf Al-Mutairi M.D., F.R.C.P., Corresponding Author Nawaf Al-Mutairi M.D., F.R.C.P. Department of Dermatology, Farwaniya Hospital, KuwaitAddress correspondence to Nawaf Al-Mutairi, M.D., F.R.C.P., P.O. Box: 280, Farwaniya, State of Kuwait, or e-mail: nalmut@usa.net.Search for more papers by this authorOsama Nour-Eldin M.D., Osama Nour-Eldin M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorArun Joshi M.D., Arun Joshi M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this authorAyman H. Hassanain M.D., Ayman H. Hassanain M.D. Department of Dermatology, Farwaniya Hospital, KuwaitSearch for more papers by this author First published: 21 July 2005 https://doi.org/10.1111/j.1525-1470.2005.22419.xCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume22, Issue4July 2005Pages 366-368 RelatedInformation

Syndromic patent ductus arteriosus: Evidence for haploinsufficientTFAP2Bmutations and identification of a linked sleep disorder

Patent ductus arteriosus (PDA) is a common congenital heart disease that results when the ductus arteriosus, a muscular artery, fails to remodel and close after birth. A syndromic form of this disorder, Char syndrome, is caused by mutation in TFAP2B, the gene encoding a neural crest-derived transcription factor. Established features of the syndrome are PDA, facial dysmorphology, and fifth-finger clinodactyly. Disease-causing mutations are missense and are proposed to be dominant negative. Because only a small number of families have been reported, there is limited information on the spectrum of mutations and resulting phenotypes. We report the characterization of two kindreds (K144 and K145) with Char syndrome containing 22 and 5 affected members, respectively. Genotyping revealed linkage to TFAP2B in both families. Sequencing of TFAP2B demonstrated mutations in both kindreds that were not found among control chromosomes. Both mutations altered highly conserved bases in introns required for normal splicing as demonstrated by biochemical studies in mammalian cells. The abnormal splicing results in mRNAs containing frameshift mutations that are expected to be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency; even if produced, the protein in K144 would lack DNA binding and dimerization motifs and would likely result in haploinsufficiency. Examination of these two kindreds for phenotypes that segregate with TFAP2B mutations identified several phenotypes not previously linked to Char syndrome. These include parasomnia and dental and occipital-bone abnormalities. The striking sleep disorder in these kindreds implicates TFAP2B-dependent functions in the normal regulation of sleep.

Feingold syndrome: clinical review and genetic mapping.

Feingold syndrome is characterized by autosomal dominant inheritance of microcephaly and limb malformations, notably hypoplastic thumbs, and clinodactyly of second and fifth fingers. Syndactyly frequently involves the second and third, as well as the fourth and fifth toes. Approximately one in three Feingold syndrome patients have esophageal or duodenal atresia or both. Anal atresia has been reported in a single case. At least 79 patients in 25 families have been reported. The syndrome has autosomal dominant inheritance with full penetrance, and variable expressivity. Vertebral anomalies, cardiac malformations, and deafness have been noted in a minority of patients. Here, we report a patient with hydronephrosis of one kidney and cystic dysplasia of the other, necessitating nephrectomy. The overall pattern of malformations in Feingold syndrome shows considerable overlap with the VATER/VACTERL association. The gene for Feingold syndrome maps to 2p23-p24, but remains to be identified. Comparison of the pattern of anomalies that occurs in the Feingold syndrome in humans and malformations that are present in mice with mutations of genes in the sonic hedgehog signaling pathway suggest, that the elusive Feingold syndrome gene may involve this signaling pathway as well.

Congenital glaucoma and Silver-Russell phenotype associated with partial trisomy 7q and monosomy 15q

We report on a 28-year-old man with trisomy 7q34-qter and monosomy 15q26.3-qter caused by a paternal balanced chromosomal translocation, t(7;15)(q34;q26.3). He had bilateral congenital glaucoma (buphthalmos), as well as typical manifestations of partial trisomy 7q. To our knowledge, this is the second description of a possible relation between congenital glaucoma and 7q trisomy. He also had some Silver-Russell syndrome features, such as short stature of prenatal onset, a characteristic triangular face, clinodactyly of the fifth fingers, and body asymmetry. Fluorescence in situ hybridization analysis on his chromosomes revealed that one copy of the insulin-like growth factor 1 receptor gene (IGF1R) at 15q25-q26 was deleted, suggesting a possible role of IGF1R in the SRS phenotype.

Imperforate anus in Feingold syndrome

A father and daughter had the characteristic findings of Feingold syndrome including microcephaly, short palpebral fissures, brachydactyly with clinodactyly of fifth fingers, and bilateral syndactyly of second to third and fourth to fifth toes. The infant presented with long-gap esophageal atresia without fistula (type A). Her father, who had short stature and learning disabilities, had congenital imperforate anus with a recto-vesical fistula. This is the first report of distal intestinal atresia in Feingold syndrome.

Interstitial deletion of the long arm of chromosome 4 [del(4)(q21.22q23)] and a liver tumor

We report on a boy with proximal interstitial deletion of chromosome 4, del(4)(q21.22q23). The patient was born at term with a low birth weight, flat nasal bridge, micrognathia, wide-spaced nipples, clinodactyly of fifth fingers, overlapping fingers, post-axial polydactyly of the right foot, micropenis, hypospadias, a dermal sinus, and cardiac malformations. He developed psychomotor retardation, seizures, and a liver tumor with an increased serum alpha-fetoprotein level and rapid growth. The patient carried a deletion of chromosome 4 involving the 4q21-q22 region that was reported to form a unique syndrome. The absence of central nervous system overgrowth and the presence of a malignant liver tumor are unique to our patient, compared to others with the 4q21-q22 deletion syndrome. The clinical manifestations and relationship between the liver tumor and chromosomal anomaly are discussed.

Partial Trisomies and Deletions of Chromosome 13

With the advent of new banding techniques there have been increasing numbers of patients with trisomies and deletions for specific portions of chromosome 13 discovered. Some authors have suggested a preliminary phenotypic mapping of chromosome 13. We have studied five patients with trisomies and deletion of parts of chromosome 13 using banding techniques and we have attempted a karyotype-phenotype correlation. 1) Deletion 13q31 13qter: karyotype 46,XX,del(13) (13pter 13q31:) is associated with mental retardation, craniofacial asymmetry, microcephaly, wide forehead, short philtrum, large mouth with protruding and wide spaced superior incisors, prominent and wide nasal bridge, large ears, hypertelorism, retinoblastoma of left eye, and kyphoscoliosis. 2) Deletion 13q31/13q32/13q33 13qter: karyotype 46,XY,13r is associated with growth and mental retardation, large eyes, epicanthus, hypertelorism, frontal bossing, high arched palate, short philtrum, protruding and wide spaced superior incisors, simple low set ears, hypoplastic fingernails, posterior prominence of heel, deep crease of hallux, dorsiflexed first toe, and a third toe longer than the other toes in both feet. 3) Trisomy 13q12--13qter: karyotype 46,X,+t(Y;13)(q11:q12)(Ypter Yq11:13q12 13qter:) is associated with trigonocephaly, craniostenosis with prominent metopic suture, epicanthus, colobomata of left iris, high arched palate, dysplastic low set ears, postaxial symmetric polydactyly, abnormal flexion of fingers, hypoplastic fingernails, and bilateral club feet. 4) Trisomy 13q13 13qter: karyotype 46,XX,t(5;13)(p14;q13)(13qter 13q13::5p14 5qter)pat. is associated with growth retardation, microcephaly, craniostenosis, sloping and prominent forehead, protruding nasal bridge, short palpebral fissures, bilateral cleft lip, cleft palate, short neck, abnormal flexion of fingers, simian crease, clinodactyly of fifth fingers, bilateral club feet, and duplication of fifth toe with syndactyly in the right foot. 5) Trisomy 13pter 13q12: karyotype 47,XX,+del(13)(13pter 13q12:) is associated with mental retardation, microophthalmy, enophthalmy, colobomata of iris and glaucoma of left eye, bilateral preauricular dimples, imperforate anus, rectovulvar fistual, and double left calyceal system.