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Partial karyotype of the propositus and her father with the corresponding ideogram. A) Propositus's karyotype redesigned as 46,XX,-5,+der5(5qter->5p15::13q22->13qter)t(5;13)pat. There is extra material on short arm of chromosome 5. B). Father's karyotype with translocation (5;13)(p15;q22).
Source publication
The partial trisomy 13q.22 is an uncommon chromosomopathy. We present a case with a partial trisomic component 13q22 and a monosomic component 5p15 from paternal origin. This patient developed early menopause and major neurological disorders as leukoencephalopathy, late onset generalised epilepsy and stroke. She also had fatty acids disturbances an...
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Material and methods
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Discussion
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Objective - To describe a rare condition in children called posterior reversible leukoencephalopathy syndrome, its causes, diagnostic approach and treatment. Case report - A 17 year old girl experienced generalized seizures and head trauma after collapsing in the toilet. It was the first seizure in her life. Five days earlier she had given birth. T...
Citations
... Possible mechanisms leading to partial trisomy 13q include parental reciprocal translocations, parental pericentric inversions, or de novo direct duplications [8]. Phenotypic features include leukoencephalopathy, epilepsy, stroke, hippocampal hypoplasia, intellectual disability, facial anomalies, olfactory hypoplasia, and cardiomyopathy [9,10]. ...
... However, despite undergoing bilateral EDAS, our patient continues to suffer from quadriplegia, intractable seizures, and spasticity in all limbs. However, our patient's findings resemble those of a report by Ribacoba et al. describing a 33-year-old female with partial trisomy 13q22 who developed leukoencephalopathy and late-onset epilepsy and stroke, and eventually passed away from nocturnal status epilepticus [9]. Brogna et al. report similar findings in a 23-year-old male with partial 13q22-q34 trisomy, who also developed seizures and leukoencephalopathy [10]. ...
... These findings reaffirm that partial trisomy 13q has been associated with refractory epilepsy, as is the case in our patient. While it has been established that the association between full trisomy 13 and seizures [31] is owed to the presence of structural lesions [9], this has yet to be proven in patients with partial trisomy. ...
Moyamoya syndrome (MMS) is a cerebrovascular disease characterized by stenosis of the internal carotid arteries and the formation of an abnormal vascular network at the base of the brain. MMS usually occurs secondary to various conditions, particularly Down syndrome, and sickle cell anemia, and presents with motor deficits, sensory symptoms, recurrent ischemic strokes, hemodynamic transient ischemic attacks, recurrent seizures, and hemorrhage. Trisomy 13 (Patau Syndrome) is a chromosomal abnormality that may be characterized by full or partial trisomy of chromosome 13. Phenotypic features of partial trisomy 13 include leukoencephalopathy, hippocampal hypoplasia, intellectual disability, facial anomalies, and others. Herein, we report a case of a 19-year-old female diagnosed with partial trisomy 13q, characterized by two large duplications in the 13q14 and 13q31 regions, with trisomy-induced bilateral MMS – the first known case to be discussed in literature. Particularly, our patient was identified to have a gain of 22Mb within the 13q14.11q21.31 region – a duplication that has not been described previously. Our patient suffered four strokes between the ages of 5 and 7, later developing intractable seizures, hemiplegia, spasticity in all limbs, global delay, and regression. Despite bilateral encephaloduroarteriosynangiosis and being on several antiepileptic medications, the MMS continued to progress, confounded by the partial trisomy 13. Studies must elucidate the association between mitochondrial damage and MMS, as well as mechanisms of epilepsy associated with chromosomal abnormalities, particularly in the context of underlying mitochondrial diseases.
... The few cases reported in the literature are related to an unbalanced translocation, while isolated de novo duplications of the distal 13 q are very rarely stated [1][2][3]. Major phenotypic features include psychomotor delay, intellectual disability and specific facial morphological anomalies as well as long philtrum, frontal bossing, stubby nose, haemangioma mainly associated to the involvement of the q22 segment and, less frequently, microcephaly, hypertelorism and hexadactyly [3,4]. Some radiological findings associated to partial 13 trisomy are leukoencephalopathy, bilateral perisylvian and rolandic cortical dysplasia, brain malformations including holoprosencephaly, callosal dysgenesis, hippocampal hypoplasia, olfactory hypoplasia, vermian hypoplasia [4]. ...
... Major phenotypic features include psychomotor delay, intellectual disability and specific facial morphological anomalies as well as long philtrum, frontal bossing, stubby nose, haemangioma mainly associated to the involvement of the q22 segment and, less frequently, microcephaly, hypertelorism and hexadactyly [3,4]. Some radiological findings associated to partial 13 trisomy are leukoencephalopathy, bilateral perisylvian and rolandic cortical dysplasia, brain malformations including holoprosencephaly, callosal dysgenesis, hippocampal hypoplasia, olfactory hypoplasia, vermian hypoplasia [4]. Similarly, epileptic seizures often occurred, related to the presence of structural cerebral lesions or to the dysfunctional neuronal neurotransmition regulation typical of the chomosomopathies. ...
... Similarly, epileptic seizures often occurred, related to the presence of structural cerebral lesions or to the dysfunctional neuronal neurotransmition regulation typical of the chomosomopathies. However, so far, only few reports described radiological findings typical of ischemic cerebral lesions related to partial 13q trisomy while the presence of stroke related to abnormal coagulation pattern is not yet well investigated [4]. We report the clinical case of a 23-year-old patient affected by de novo partial 13q22-q34 trisomy (41.7 Mb) presenting with hemiparesis related to both ischemic and haemorrhagic cerebral lesions compatible with cerebral vasculitis associated with immunological findings. ...
The partial trisomy 13q encompasses an extensive variability of phenotypic and radiological findings including leukoencephalopathy and brain malformations such as holoprosencephaly, callosal dysgenesis, hippocampal hypoplasia, olfactory hypoplasia, and vermian hypoplasia. We report for the first time a case of a 23-year-old patient affected by de novo partial 13q22.1q34 trisomy (41.7 Mb, 72,365,975-114,077,122x3) presenting with hemiparesis related to both ischemic and haemorrhagic cerebral lesions compatible with cerebral vasculitis due to a possible combination of genetic and immunological interaction.
... Included is a patient with vascular leukoencephalopathy and recurrent CVAs at 44 years with a CNV encompassing COL4A1 and COL4A2 along with 43 additional genes 3 and a patient with leukoencephalopathy, late-onset generalized epilepsy, and recurrent CVAs beginning at age 33 with partial monosomy of chromosome 5 and a large duplication of chromosome 13. 4 For our family, as well as for these aforementioned cases, the constant clinical finding is the presence of CSVD. ...
Objective:
While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005).
Conclusions:
COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.
... However, at present, this hypothesis remains unproven. 1,12 The diagnosis of West syndrome is often easy when infantile spasms are associated with arrest or regression of psychomotor development, and a specific EEG pattern of hypsarrhythmia. 8 The clinical symptoms of infantile spasms are very different from any other type of seizure because of the absence of paroxysmal motor phenomena, such as convulsions or loss of consciousness. ...
Trisomy 13, or Patau syndrome, is a rare chromosomal disorder characterized by a triad of cleft lip and palate, postaxial polydactyly, and microphthalmia, with an incidence ranging between 1/5,000 and 1/20,000 births.1 Most patients (80%) with Patau syndrome have complete trisomy 13. Mosaic trisomy 13 is very rare; it occurs in only 5% of all patients with the trisomy 13 phenotype.2 Trisomy 13 is a clinically severe entity, and 90 to 95% of patients born with this syndrome do not survive beyond one year of life. However, patients with mosaic trisomy 13 usually have longer survival and less severe phenotype compared to patients with complete trisomy 13. Malformations mainly affect midline development, with a high frequency of central nervous system involvement. The presence of central nervous system malformations is important as a predictive factor of survival.1,3 It is well known that the incidence of epilepsy is higher in children with Patau syndrome than in the general population, and West syndrome or infantile spasms have been rarely reported in these children.1,4,5 Prior to our report, there has been no case report of West syndrome associated with mosaic trisomy 13. The association of West syndrome with trisomy 13 is considered a symptomatic West syndrome because of preexisting psychomotor development delay and the poor prognosis in most of these children.6 We report here the first case of West syndrome in a girl with mosaic trisomy 13 and discuss the clinical characteristics and prognosis of this association.
... Included is a patient with vascular leukoencephalopathy and recurrent CVAs at 44 years with a CNV encompassing COL4A1 and COL4A2 along with 43 additional genes 3 and a patient with leukoencephalopathy, late-onset generalized epilepsy, and recurrent CVAs beginning at age 33 with partial monosomy of chromosome 5 and a large duplication of chromosome 13. 4 For our family, as well as for these aforementioned cases, the constant clinical finding is the presence of CSVD. ...
... However, the few reported cases most often result from unbalanced translocation derivatives with concomitant monosomy of a portion of another chromosome, complicating these comparisons. One adult patient was reported with learning disabilities, leukoencephalopathy, seizures, premature menopause, and stroke with an unbalanced translocation derivative with concomitant loss of 5p [Ribacoba et al., 2008]. Helali et al. [1996] reported a boy with a mild phenotype consisting of psychomotor delay, tethered cord, and mildly dysmorphic features with a paternally derived unbalanced translocation derivative with duplication of 13q32qter and deletion of distal 18p. ...
Constitutional chromoanagenesis events, which include chromoanasynthesis and chromothripsis and result in highly complex rearrangements, have been reported for only a few individuals. While rare, these phenomena have likely been underestimated in a constitutional setting as technologies that can accurately detect such complexity are relatively new to the mature field of clinical cytogenetics. G-banding is not likely to accurately identify chromoanasynthesis or chromothripsis, since the banding patterns of chromosomes are likely to be misidentified or oversimplified due to a much lower resolution. We describe a patient who was initially referred for cytogenetic testing as a child for speech delay. As a young adult, he was referred again for recurrent strokes. Chromosome analysis was performed, and the rearrangement resembled a simple duplication of 13q32q34. However, SNP microarray analysis showed a complex pattern of copy number gains and a loss consistent with chromoanasynthesis involving distal 13q (13q32.1q34). This report emphasizes the value of performing microarray analysis for individuals with abnormal or complex chromosome rearrangements.
... A preferential predisposition for absence seizures has also been linked to 13q22-q31 (Hempelmann et al. 2006). Singular cases of epilepsy combined with other neurological disorders or mental retardation have been linked to 13q22 and to SLC4A10, or solute carrier family 4, sodium bicarbonate transporter, member 10 in 13q31 (Gurnett et al. 2008;Ribacoba et al. 2008). However, locus 13q14.2, a region possibly cosegregating with two of the Honduran pedigrees under investigation, has not been previously associated with epilepsy, but has been linked to visual migraine aura (Tikka-Kleemola et al. 2010). ...
Juvenile myoclonic epilepsy (JME), the most common genetic epilepsy, remains enigmatic because it is considered one disease instead of several diseases. We ascertained three large multigenerational/multiplex JME pedigrees from Honduras with differing JME subsyndromes, including Childhood Absence Epilepsy evolving to JME (CAE/JME; pedigree 1), JME with adolescent onset pyknoleptic absence (JME/pA; pedigree 2), and classic JME (cJME; pedigree 3). All phenotypes were validated, including symptomatic persons with various epilepsies, asymptomatic persons with EEG 3.5–6.0 Hz polyspike waves, and asymptomatic persons with normal EEGs. Two-point parametric linkage analyses were performed with 5185 single-nucleotide polymorphisms on individual pedigrees and pooled pedigrees using four diagnostic models based on epilepsy/EEG diagnoses. Haplotype analyses of the entire genome were also performed for each individual. In pedigree 1, haplotyping identified a 34 cM region in 2q21.2–q31.1 cosegregating with all affected members, an area close to 2q14.3 identified by linkage (Zmax = 1.77; pedigree 1). In pedigree 2, linkage and haplotyping identified a 44 cM cosegregating region in 13q13.3–q31.2 (Zmax = 3.50 at 13q31.1; pooled pedigrees). In pedigree 3, haplotyping identified a 6 cM cosegregating region in 17q12. Possible cosegregation was also identified in 13q14.2 and 1q32 in pedigree 3, although this could not be definitively confirmed due to the presence of uninformative markers in key individuals. Differing chromosome regions identified in specific JME subsyndromes may contain separate JME disease-causing genes, favoring the concept of JME as several distinct diseases. Whole-exome sequencing will likely identify a CAE/JME gene in 2q21.2–2q31.1, a JME/pA gene in 13q13.3–q31.2, and a cJME gene in 17q12.
... Trisomy of 13q is more frequently a result of parental balanced translocation or pericentric inversion rather than of de novo duplication [25]. Most of the features present in patients with partial trisomy 13q are also present in patients with full chromosome 13 trisomy which results in Patau syndrome (PS). ...
... In about 80% of PS patients holoprosencephaly with characteristic dysmorphy of midface (e.g. proboscis), cleft lip and palate, small dysplastic earlobes, microcephaly, and hypotelorism are also present [25,26]. In patients with partial 13q trisomy holoprosencephaly occurs rarely, most often when trisomic region includes 13q11-q14 [26]. ...
Balanced complex translocations (BCTs) are rare events, they may result in reproductive failures: spontaneous abortions, missed abortions, stillbirths, congenital malformations in children, and male infertility. BCTs belong to the group of complex chromosome rearrangements (CCRs) - up to date about 260 cases were described.
The described patient and her husband were referred to genetic counseling clinic because of four reproductive failures. GTG-banded chromosome analysis revealed presence of apparently balanced complex translocation t(2;5;13), which was verified and confirmed by molecular cytogenetics with single copy probes. This complex aberration was most likely responsible for reproductive failures in our patient. Since no high resolution molecular karyotyping (microarrays) was used, this rearrangement can only be considered to be balanced at cytogenetic level.
Due to small number of reported cases of CCRs/BCTs and individual as well as unique character of such rearrangements, genetic counseling for CCRs carriers is complex and requires detailed pedigree analysis, as well as extended clinical and genetic testing.
... The published cases of partial trisomy 13q helped to delineate the variable phenotype associated with this chromosomopathy (Rivas et al., 1984; Tharapel et al., 1986; Nikolis et al., 1991; Rodriguez de Alba et al., 1999; Chen et al., 2005a,b; Lin et al., 2007; Ribacoba et al., 2008). Common phenotypic features described for partial trisomy 13q are: craniofacial dysmorphism (bushy Figure 2. Array comparative genomic hybridization spectral view of chromosome 13 (A) and 4 (B) of the fetus (Constitutional Chip 4.0). ...
... Although the association of congenital diaphragmatic hernia and trisomy 13 has been described, complete bilateral agenesis of the diaphragm is a rare congenital diaphragmatic hernia variant with no previously described chromosomal aberration etiology. The published cases of partial trisomy 13q helped to delineate the variable phenotype associated with this chromosomopathy (Rivas et al., 1984; Tharapel et al., 1986; Nikolis et al., 1991; Rodriguez de Alba et al., 1999; Chen et al., 2005a,b; Lin et al., 2007; Ribacoba et al., 2008 ). Common phenotypic features described for partial trisomy 13q are: craniofacial dysmorphism (bushy eyebrows, long curled eyelashes, prominent nasal bridge, long philtrum, thin upper lip, microcephaly , and hypotelorism), highly arched palate, short neck, hemangioma, hexadactyly, urinary tract/ kidney anomalies, umbilical/inguinal hernia, intra-uterine growth retardation, and oligohydramnios . ...
Partial trisomy 13q is an uncommon chromosomal abnormality with variable phenotypic expression. We report prenatal diagnosis of partial trisomy 13q in a fetus with partial agenesis of the cerebellar vermis, partial agenesis of the corpus callosum, hydrops and polyhydramnios. G-banding karyotyping, spectral karyotyping and array comparative genomic hybridization (aCGH) analysis of fetal blood were performed. Cytogenetic analysis of fetal blood displayed 46,XX,add(4)(q28). The parental karyotypes were normal. A girl was delivered at 34 weeks gestation; she died within 2 h. Autopsy confirmed all the prenatal findings and also showed agenesis of the diaphragm. Spectral karyotyping identified the additional material's origin as chromosome 13. aCGH was carried out and showed amplification of distal regions of the long arm of chromosome 13 from region 13q14 to qter. This is the first report of a fetus with molecular characterization of a partial trisomy 13q (q14-->qter), present as a de novo unbalanced translocation at chromosome 4q. This case demonstrates the usefulness of molecular characterization of malformed fetuses for prenatal diagnosis and counseling.
... In letteratura non sono riportati casi in cui la duplicazione della regione in 13q fosse causa di fenotipi riconducibili alle caratteristiche cliniche di questo paziente; è pertanto possibile che si tratti di un polimorfismo anche se per tale conferma sono necessari ulteriori accertamenti 28,29 . ...
Background. Subtelomeric rearrangements have been reported to be an important cause of mental retardation. These aberrations may remain undetected by routine conventional cytogenetic analysis because of limited resolution in light microscopy. Increased detection of cryptic subtelomeric abnormalities may be achieved by Fluorescence In Situ Hybridization (FISH) which is the most widely used technique in cytogenetic laboratories. However, this assay is expensive and time consuming, because metaphase spreads are needed. Accordingly, FISH is not indicated for broad screening. Multiplex Ligation-dependent Probe Amplification (MLPA) is a new reliable, sensitive and inexpensive technique, which can be used as a high throughput prospective screening tool for subtelomeric rearrangements. The aim of this study was to introduce a novel strategy for the screening of subtelomeric rearrangements in routine diagnosis which consists in a first screening with MLPA then followed by FISH analysis. Methods. We tested 70 children with idiopathic mental retardation both severe and mild, often associated with congenital malformations, growth retardation and/or dysmorphic features. MLPA was performed using SALSA P036E human telomere kit (MRC-Holland, Amsterdam, The Netherlands). If an aberrant MLPA result was observed, FISH with a probe specific for the region of interest was performed to validate the result. Results. Among 70 patients tested, 5 were carriers of unbalanced rearrangements. 3 patients had deletion of 6pter, 2qter and 6qter respectively, one showed a double aneusomy: a distal 21q deletion and 7q duplication and the other one showed a duplication of 13qter. Conclusions. Our preliminary data show a high degree of agreement between MLPA and FISH suggesting that MLPA might be a rapid, accurate, reliable and cost-effective technique for the screening of subtelomeric rearrangements in routine diagnostics.
