Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of subtelomeric FISH probes has greatly supplemented conventional chromosome analysis in detecting cryptic anomalies in patients with mental retardation (MR), dysmorphic features, and congenital malformations. We report a 3-month-old boy who was diagnosed with ambiguous genitalia, dysmorphic features, and developmental delay. Standard chromosome studies on blood revealed a chimeric karyotype of 46,XY,t(4;5)(q31.1;q14)[46]/46,XX[4]. The boy had intra-abdominal gonads that were testicular in origin by biopsy. Multiple dysmorphic features, marked hypotonia, developmental delay, poor growth, and relative macrocephaly were noted on physical exam. His 2.5-year-old sister also presented with hypotonia, developmental delay, relative macrocephaly, and similar dysmorphic stigmata. In addition, she was diagnosed with several internal malformations. Her karyotype was 46,XX. Due to the striking phenotypic similarity, subtelomeric FISH studies were initiated in the siblings. In addition to the known balanced karyotypic abnormalities, the boy was found to have a derivative chromosome 5 with a 5pter deletion and a 17pter duplication. This cryptic abnormality was also detected in his sister. Chromosome analysis of the father revealed a subtle balanced t(5;17)(p15.31;p13.1) which was confirmed by subtelomeric FISH, whereas the mother's chromosome complement was normal. This familial constellation illustrates the usefulness of subtelomeric FISH in the diagnosis of cryptic chromosome abnormalities in patients for whom conventional karyotype does not disclose findings sufficient to explain the observed phenotypic anomalies.
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PMID:Unbalanced cryptic 5p deletion/17p duplication identified by subtelomeric FISH in a family with a boy with chimerism and a balanced t(4;5). 1475 72

A rec(5)dup(5)(q23.2q31.3) inherited from a maternal ins(5)(p13.1q23.2q31.3) was detected in a 4-month-old male child who showed hypotonia, microcephaly, cardiac defects, pulmonary hypoplasia and stenosis, bilateral hydronephrosis, hydrocele, testicular hypoplasia and phimosis. Dysmorphisms were also observed. We compare the clinical characteristics of our patient with those of the previously reported dup5q cases in an attempt to define the phenotype-karyotype correlation. The maternal insertion responsible for the duplicated 5q23.2-31.3 region in the child was characterized in detail by FISH analysis, which identified a complex rearrangement involving four breakpoints (bkp's): a 5q segment excised following breakage at 5q23.2 and 5q31.3 became inverted and inserted at 5p13.1, probably coincidentally with an internal breakage at 5q23.3 causing a 180 degrees rotation of the two subsegments. The mother's karyotype was consequently defined as 46,XX, ins(5)(pter --> p13.1 Colon, two colons q23.3 --> q23.2 Colon, two colons q31.3 --> q23.3 Colon, two colons p13.1 --> q23.2 Colon, two colons q31.3 --> qter). There are clusters of Alu sequences in the genomic clones spanning all the four bkp's, suggesting their possible involvement in the rearrangement. No clinical phenotype was associated with this balanced rearrangement in the mother and a number of other carriers in the same family.
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PMID:Unbalanced segregation of a complex four-break 5q23-31 insertion in the 5p13 band in a malformed child. 1505 94

Canavan disease is characterised as a rare, neurodegenerative disease that usually causes death in early childhood. It is an autosomal recessive disorder due to an aspartoacylase (ASPA) deficiency. The causative gene has been mapped to chromosome 17 pter-p13. Here we describe three affected children from two Greek families with an unusually mild course of Canavan disease. All children presented with muscular hypotonia and macrocephaly. Diagnosis was based on elevated N-acetylaspartate in urine, reduced aspartoacylase activity in fibroblasts, and marked white matter changes on cerebral imaging. All three affected individuals exhibited continuous psychomotor development without any regression. Genetic analyses revealed compound heterozygous mutations (Y288 C; F295 S) in two individuals. The Y288 C variant was previously described in a child with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia, partial cortical blindness and retinitis pigmentosa, and slightly elevated N-acetylaspartate in the urine. Demonstration of the same variant in two unusually mildly affected Canavan disease patients and absence of this variant in 154 control chromosomes suggest a possible pathogenic role in mild Canavan disease. In the third individual, two homozygous sequence variants were identified, which comprise the known G274R mutation and a novel K213E variant.
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PMID:Possible genotype-phenotype correlations in children with mild clinical course of Canavan disease. 1613 49

In recent years, subtelomeric rearrangements have been identified as a major cause of multiple congenital anomalies (MCA)/mental retardation (MR) syndromes. Currently, more than 2,500 individuals with MR have been tested and subtelomeric rearrangements were detected in about 6%. Therefore, subtelomeric FISH analysis is indicated as a second tier test after high-resolution G-banding analysis, in subjects with otherwise unexplained developmental delay/MR and/or MCA. We describe a female patient and her maternal aunt, both showing a distinct phenotype, associated with the same complex subtelomeric rearrangement. Subtelomeric FISH testing performed between 1 year 9 months and 20 years after the initial karyotype showed, in both patients, distal trisomy 12p and distal monosomy 10p as follows: 46,XX.ish der(10)t(10;12)(p15.3;p13.31). Parental subtelomeric FISH analysis showed the proposita's mother (sister of Patient 2) and grandmother (mother to Patient 2), to have a balanced 10p:12p translocation. Both girls showed a similar phenotype with pre/postnatal growth retardation, moderate-to-severe developmental delay/MR, very poor/absent speech, hypotonia, lax ligaments, and a distinct pattern of malformation. On examination there were blepharophimosis; bilateral ptosis/epicanthus; broad, depressed nasal bridge with a beaked nose; short philtrum; low-set, posteriorly rotated, overfolded ears; micrognathia; mild webbing of the neck; mild broadening of thumbs; puffy hands/feet; long hallux; and sacral/coccygeal dimples. A slow overall improvement was seen in both patients over time. To our knowledge, a complex subtle rearrangement as the one seen in our patients has not been reported thus far. Our patients show features of partial 10p deletion syndrome rather than those of partial duplication 12p, confirming the general rule that deletions are more phenotypically penetrant than duplications.
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PMID:Subtelomeric analysis detects a familial 10p;12p rearrangement in two relatives with a distinct syndrome. 1716 46

Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of the chromosomal breakpoints and mechanisms involved. Here, we report a molecular cytogenetic analysis of two patients with congenital anomalies and unbalanced de novo CCRs involving chromosome 17p using high-resolution array-based comparative genomic hybridization (array CGH) and fluorescent in situ hybridization (FISH). In the first patient, a 4-month-old boy with developmental delay, hypotonia, growth retardation, coronal synostosis, mild hypertelorism, and bilateral club feet, we found a duplication of the Charcot-Marie-Tooth disease type 1A and Smith-Magenis syndrome (SMS) chromosome regions, inverted insertion of the Miller-Dieker lissencephaly syndrome region into the SMS region, and two microdeletions including a terminal deletion of 17p. The latter, together with a duplication of 21q22.3-qter detected by array CGH, are likely the unbalanced product of a translocation t(17;21)(p13.3;q22.3). In the second patient, an 8-year-old girl with mental retardation, short stature, microcephaly and mild dysmorphic features, we identified four submicroscopic interspersed 17p duplications. All 17 breakpoints were examined in detail by FISH analysis. We found that four of the breakpoints mapped within known low-copy repeats (LCRs), including LCR17pA, middle SMS-REP/LCR17pB block, and LCR17pC. Our findings suggest that the LCR burden in proximal 17p may have stimulated the formation of these CCRs and, thus, that genome architectural features such as LCRs may have been instrumental in the generation of these CCRs.
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PMID:Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies. 1745 15

We report two cases of deletion 5p or cri du chat syndrome (CdCS) with different presentations and risks of transmission: one case with paternal chromosome 5 involvement and another, a de novo case with atypical clinical presentation. Cytogenetic analysis was performed on the two cases and their parents. GTG-banded karyotype analysis of Cases 1 and 2 revealed abnormal 46,XY,del(5)(p13-15) male karyotypes. For Case 1, the mother showed normal female karyotype while the father showed an abnormal karyotype involving a balanced translocation 46,XY,t(5;10)(p13;p15). For Case 2, however, both parents showed a normal karyotype pattern. In Case 1, the clinical features, particularly the distinct facial phenotype in combination with a characteristic cat-like cry and hypotonia, aided in the diagnosis at birth and the karyotype analysis was resolutive. The boy in Case 2 presented with atypical clinical features. Even though this patient had multiple syndromic features, the typical high pitched cat-like cry was not prominent. Instead, the patient manifested persistent stridor (from day three of life), which might have prevented the clinician from suspecting CdCS at birth. However, when this patient was presented at seven months of age for cytogenetic analysis, a confirmatory diagnosis of CdCS was established. For children with congenital abnormalities, an early clinical diagnosis confirmed through cytogenetic and molecular investigations, is important for providing personalised diagnostic and prognostic evaluation, and also for genetic counselling on the reproductive risk, particularly for patients with parental chromosome translocation involvement.
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PMID:Two cases of deletion 5p syndrome: one with paternal involvement and another with atypical presentation. 1841 16

4p Monosomy and 12p trisomy have been discussed and redefined along with recently reviewed chromosomal syndromes. 12p Trisomy syndrome is characterized by normal or increased birth weight, developmental delay with early hypotonia, psychomotor delay, and typical facial appearance. Most likely, the observed phenotypic variability depends on the type and extent of the associated partial monosomy. Partial deletions of the short arm of one chromosome 4 cause the Wolf-Hirschhorn syndrome (WHS). Affected patients present Greek helmet face, growth and mental retardation, hypotonia, and seizures. The combination of these characteristics constitutes the phenotypic core of WHS. We present a clinical and molecular cytogenetic characterization of a 4-year old mentally retarded girl with macrosomy, facial dysmorphisms, and epilepsy, in whom an unbalanced t(4;12)(p16.3;p13.3) translocation was detected, giving rise to partial 4p monosomy and partial 12p trisomy. Because the patient shows most of the phenotypic characteristics of 12p trisomy, this case could contribute to a better definition of the duplicate critical region that determines the phenotype of the 12p trisomy syndrome.
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PMID:Trisomy 12p and monosomy 4p: phenotype-genotype correlation. 1937 4

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.
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PMID:Inv dup del(4)(:p13-->p16.3::p16.3-->qter) in a girl without typical manifestations of Wolf-Hirschhorn syndrome. 1944 29

Interstitial deletions of chromosome band 10q22 are rare. We report on the characterization of three overlapping de novo 10q22 deletions by high-resolution array comparative genomic hybridization in three unrelated patients. Patient 1 had a 7.9 Mb deletion in 10q21.3-q22.2 and suffered from severe feeding problems, facial dysmorphisms and profound mental retardation. Patients 2 and 3 had nearly identical deletions of 3.2 and 3.6 Mb, the proximal breakpoints of which were located at an identical low-copy repeat. Both patients were mentally retarded; patient 3 also suffered from growth retardation and hypotonia. We also report on the results of breakpoint analysis by array painting in a mentally retarded patient with a balanced chromosome translocation 46,XY,t(10;13)(q22;p13)dn. The breakpoint in 10q22 was found to disrupt C10orf11, a brain-expressed gene in the common deleted interval of patients 1-3. This finding suggests that haploinsufficiency of C10orf11 contributes to the cognitive defects in 10q22 deletion patients.
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PMID:Chromosome aberrations involving 10q22: report of three overlapping interstitial deletions and a balanced translocation disrupting C10orf11. 1984 53

Congenital balanced reciprocal translocations are one of the most frequent structural chromosomal aberrations in the population. We report a familial translocation t(12;22)(p13.3;pter) responsible for intellectual disabilities and congenital anomalies characterized by FISH and array CGH. Two patients carried a der(12)t(12;22)(p13.3;pter), resulting in a 6 Mb 12pter deletion. Patients presented with intellectual disabilities, pre- and post-natal growth retardation, ponderal development delay, global hypotonia, feeding problems and dysmorphic features. Two relatives presented with the reciprocal 12pter duplication, which had no clinical manifestations associated. For this translocation, we propose a mechanism based on a non-allelic recombination model, in which recombination of direct oriented segmental duplications between non-homologous chromatids leads to the reciprocal translocation. The characterization of this translocation has been critical for the family. Translocation carriers have a risk of 40% of having offspring carrying unbalanced products. 12p13.3 deletion carriers present with a recognizable syndrome and on the contrary, 12p13.3 duplication carriers present without clinical manifestations. Other published cases of 12p13.3 duplication show that this syndrome has a variable phenotype. It is advisable to delineate the duplication size and to discard other genetic aberrations, in order to give an accurate genetic counseling in patients carrying 12pter duplications.
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PMID:12p13 rearrangements: 6 Mb deletion responsible for ID/MCA and reciprocal duplication without clinical responsibility. 2248 86


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