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Phenotypical and chromosomal characteristics of the affected members of the family showing 18p deletion (arrow). Proband (A, D), sister (B, E) and mother (C, F).
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Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases.
The...
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An imbalance of genetic material, especially monosomy, will usually give rise to an abnormal phenotype. A few instances of proximal 2q deletions have been published, but previous cases (q12-q14,1 q12-q14.2,2 q14-q213 4) have been associated with clinical features such as mental retardation, facial dysmorphism, heart defects, and renal and digital a...
Citations
... 4 However, skeletal or brain malformations, mostly of the holoprosencephaly, have also been reported. [5][6][7] In most patients (>75%), deletions are seen de novo. 8 The rest are caused by de novo translocation or imbalanced familial transmission of structural rearrange-ments. ...
The frequency of 18p deletion syndrome is estimated to be ∼1/50,000 live births and is more commonly associated with certain clinical features including short stature, intellectual disability, and facial dysmorphism. Physical examination of our patient revealed a short stature, intellectual disability, facial dysmorphism (microcephaly, ptosis, epicanthus, low nasal bridge, protruding ears, long philtrum, and thin lips), and clinodactyly of the fifth finger. The peripheral karyotype was 46, XX, del (18) (p11.32p11.2). DNA microarray analysis revealed a de novo 13.9-Mb deletion at 18p11.32p.11.21. Echocardiography revealed asymmetric septal hypertrophy. Congenital cardiac abnormalities are present very rarely in this syndrome. This finding suggests that one locus or loci that play a role in cardiac development is located in this chromosomal region. Although rare, cardiac hypertrophies should be kept in mind when evaluating a patient with phenotypic anomalies and genetic results compatible with an 18p deletion syndrome.
... [9][10][11][12] To our knowledge, the familial transmission of the chromosome 18p deletion syndrome is very rare, and no >10 cases were reported. [13][14][15][16][17][18][19][20] Almost all of the familial transmissions of the 18p deletion syndrome were delivered from a mother to a child, and the phenotypes of the 2 generations were similar. In our report, the 18p deletion syndrome is transmitted from the woman to her fetus in case 1. ...
Rationale:
The chromosome 18p deletion syndrome is a syndrome with a deletion of all or a portion of the short arm of the chromosome 18. The phenotypes of the chromosome 18p deletion syndrome vary widely among individuals due to differences in size and breakpoints and the involved genes on the deletions. Given the varied and untypical clinical presentation of this syndrome, the prenatal diagnosis of the syndrome still presents as a challenge.
Patient concerns:
We described 4 China cases with different chromosomal breakpoints. In case 1, a woman who with mild phenotypes gave birth to a severely deformed fetus. Three other cases were for prenatal diagnosis. Their phenotypes are the increased nuchal translucency (INT) and the noninvasive prenatal testing (NIPT) indicated deletions on the chromosome 18p and severe hydronephrosis respectively.
Diagnosis:
The 4 cases were diagnosed with chromosome 18p deletion syndrome through karyotype analysis and array-based comparative genomic hybridization (array-CGH).
Interventions:
Karyotype analysis and array-based comparative genomic hybridization were used to analyze the abnormal chromosome.
Outcomes:
Case 1 and case 2 revealed 11.51 and 12.39 Mb deletions in 18p11.32p11.21. Case 3 revealed 7.1 Mb deletions in 18p11.3218p11.23. Case 4 revealed 9.9 Mb deletions in 18p11.3218p11.22.
Lessons:
In our report, we are the first to report that mother and progeny who have the same chromosomal breakpoint have different phenotypes, significantly. In addition, we found a new phenotype of chromosome 18p deletion syndrome in fetus, which can enrich the phenotypes of this syndrome in the prenatal diagnosis. Finally, we demonstrate that the individuals with different chromosomal breakpoints of 18p deletion syndrome have different phenotypes. On the other hand, the individuals with the same chromosomal breakpoints of 18p deletion syndrome may also have remarkably different phenotypes.
... Most of the affected cases are fertile and normal in puberty. 1,8 A majority of 18p-cases are supposed to originate from de novo deletions, whereas the remainder is suspected to come from unbalanced chromosomal abnormalities involving chromosome 18 or imbalanced familial transmission of structural rearrangements. 1,6,8,9 Notably, a great number of 18p-cases were diagnosed at elder children or adults while the prenatal detection rate of those cases has been limited due to the nonspecific indications by ultrasound, except for the severe malformations pertaining to the holoprosencephaly spectrum which has an incidence rate of approximately 10%. ...
... 1,8 A majority of 18p-cases are supposed to originate from de novo deletions, whereas the remainder is suspected to come from unbalanced chromosomal abnormalities involving chromosome 18 or imbalanced familial transmission of structural rearrangements. 1,6,8,9 Notably, a great number of 18p-cases were diagnosed at elder children or adults while the prenatal detection rate of those cases has been limited due to the nonspecific indications by ultrasound, except for the severe malformations pertaining to the holoprosencephaly spectrum which has an incidence rate of approximately 10%. 7,8,[10][11][12] Here, we report a Vietnamese girl with a 9.9 Mb pure deletion at 18p11.32-11.22, ...
... 1,6,8,9 Notably, a great number of 18p-cases were diagnosed at elder children or adults while the prenatal detection rate of those cases has been limited due to the nonspecific indications by ultrasound, except for the severe malformations pertaining to the holoprosencephaly spectrum which has an incidence rate of approximately 10%. 7,8,[10][11][12] Here, we report a Vietnamese girl with a 9.9 Mb pure deletion at 18p11.32-11.22, who only presented the increased nuchal translucency (3.9 mm) in the first trimester screening and whose prenatal diagnosis by QF-PCR (Quantitative Fluorescence -Polymerase Chain Reaction) did not detect 21, 18, 13 and sex chromosomal aneuploidy. ...
Quantitative Fluorescent-Polymerase Chain Reaction (QF-PCR) is a rapid prenatal diagnosis test for 21, 18, 13 and sex chromosomal aneuploidy detection. However, it could not detect partial trisomy or partial monosomy of those chromosomes. Here, we report a 19-month-old Vietnamese female with a 9.9 Mb pure deletion of chromosome 18 at 18p11.32-11.22 confirmed by next generation sequencing. The patient was short statured with facial dysmorphic features as well as motor skill and speech delays. First trimester screening showed high risk of trisomy 21 with only increased nuchal translucency (NT 3.9 mm) by ultrasound as an indication. Prenatal diagnosis by QF-PCR from amniotic DNA revealed normal disomy. Noticeably, two short tandem repeat (STR) markers D18S391 and D18S976 located on 18p exhibited uninformative patterns (one peak). Thus, our case suggested that the combination of both D18S391 and D18S976 markers with uninformative patterns in QF-PCR for prenatal diagnosis and increased NT in the first trimester ultrasound may be a significant indication of 18p monosomy.
... Rarely, monosomy 18p patients may be affected with holoprosencephaly, leading to profound neurologic abnormalities, seizures, mental retardation, cleft lip, cleft palate, ocular hypotelorism, and rarely cyclopia. 21 In males, cryptorchidism and hypospadias have been reported. Very rarely in females, hypoplastic external genitalia and gonadal dysgenesis may be present. ...
Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome and 18p deletion syndrome, two genetic disorders having distinct genetic etiologies, have an exceedingly rare likelihood of coexistence. Vaginal agenesis or MRKH syndrome, the developmental failure of Mullerian ductal system-derived structures in a genotypic female fetus (46, XX), leads to congenital absence of uterus and vagina in variable degree. The 18p deletion syndrome is a rare chromosomal disorder, characterized by dysmorphic features, stunted growth, and mental retardation, which is caused by deletion of a part or all of the short arm of chromosome 18. A detailed evaluation of primary amenorrhea in a 16-year-old girl yielded both MRKH syndrome and 18p deletion syndrome. Extensive literature search could not identify any reported case bearing this combination of syndromes. This case presentation and review emphasizes on the importance of karyotyping in MRKH patients having atypical features.
... The incidence of the disorder could be estimated to be about 1:50,000 live-born infants worldwide. [1] The most common clinical features of 18p deletion syndrome include cognitive disorders, growth retardation and mild facial deformity (e.g., low nasal bridge, protruding ears). [2] Most of the cases have a de novo pure terminal deletion. ...
... [3] Majority cases were accidentally diagnosed while undergoing clinical evaluation for abnormal clinical manifestations, such as short stature, mental retardation. [1,4] The survival outcome of this syndrome varies widely from months to decades depending on the severity. [5] Moreover, 18p deletion may influence the intelligence development. ...
... [2,3] It has been revealed family members affected by an identical 18p deletion have significantly variable intelligence levels. [1] However, currently, there is no specific treatment for 18p deletion, except speech therapy and early educational programs may help to improve the performances of the children. [3] Therefore, the prenatal diagnosis of monosomy 18p syndrome is important for early prevention and management. ...
Rationale:
Monosomy 18p deletion syndrome refers to a rare chromosomal disorder resulting from the part deletion of the short arm of chromosome 18. Prenatal diagnosis of de novo 18p deletion syndrome is a challenge due to its low incidence and untypical prenatal clinical presentation.
Patient concerns:
Three cases received amniocentesis due to increased nuchal translucency (INT), high risk for Down syndrome, and INT combined intrauterine growth retardation (IUGR), respectively.
Diagnosis:
The 3 cases were diagnosed with de novo monosomy 18p deletion syndrome by amniocentesis and chromosome microarray analysis (CMA).
Interventions:
Karyotype analysis and CMA were used to analyze the abnormal chromosome.
Outcomes:
Case 1 and case 2 revealed 13.87 and 12.68 Mb deletions by array-CGH analysis, respectively. Case 3 revealed 6.9 Mb deletions in 18p11.32p11.31 and 7.5 Mb deletions in 18p11.23p11.21 by single nucleotide polymorphism array. All of the pregnancies were terminated due to the abnormal chromosome.
Lessons:
The fetal phenotype of monosomy 18p deletion syndrome shows great variability and may not be evident during the pregnancy. CMA may be served as an effective tool for the diagnosis of prenatal monosomy 18p deletion syndrome diagnosis.
... So, it is also called as de Grouchy syndrome. Phenotypic variability of this syndrome makes it difficult to recognize [6]. ...
... TGIF1 (TG-interacting factor 1) and SMCHD1 (Structural maintenance of chromosome flexible hinge domain containing 1). Many phenotypical features of this case were very similar to the other reported cases that listed out in Table 1 [3,6,12,13]. Our case characteristically was presented with delayed and slowly growth, gastroesophageal reflux, learning difficulties, postponement of speech, difficulty communicating, short stature, short neck, small and slightly receding chin or lower jaw, lowset ear, low posterior hairline, gross motor skills, decay and irregular dentition, ptosis, and scoliosis. ...
Background: The common causes of 18p deletion syndrome are spontaneous errors in the chromosomal structure in the early stages of human embryonic development. Clinical Presentation and Intervention: In this study, a 29-year-old girl was introduced with the features of deletion of chromosome 18. In addition, GTG banding karyotype revealed that this case had a deletion involving the short arm of chromosome 18. In comparison with the usual phenotype of 18p deletion, many phenotypical features of this case were similar to the other cases of 18p monosomy. Conclusion: However, two new features; difficulty in speaking and persistent limb tremor, were found that had not been observed in previous studies on the 18p deletion. Speaking was without obvious pronunciation, and the patient's physical movements were always unbalanced. These two features can be new signs for 18p deletion syndrome.
... У осталим случајевима постоји трансмисија с родитеља, и то у случајевима када су родитељи носиоци балансиране транслокације, а такође монозомија 18p може настати као резултат небалансиране транслокације целог крака хромозома 18 у око 16% случајева. Забележени су случајеви фамилијарне трансмисије монозомије 18p с родитеља на потомке (2,3). Монозомија 18p може се јавити и у форми мозаика, у случајевима ринг хромозома 18 или након рекомбинације код родитеља носилаца перицентричне инверзије хромозома 18, што може да доведе до парцијалне монозомије 18 или парцијалне тризомије 18 код потомака (4). ...
... Абнормалности постају уочљивије након треће године живота (12). Обично постоје ментална ретардација различитог степена, постнатални застој у расту, низак раст, као и касни развој говора код деце (1,3,6). Постоји значајна дискрепанца између вербалних и невербалних способности, при чему су вербалне озбиљно нарушене (12). ...
Monosomy 18p (de Grouchy syndrome 1) is a structural
chromosome aberration provoked by the deletion of a part of
or the entire 18 chromosome's short arm. In 2/3 of cases it is
provoked because of the de novo terminal deletion of 18
chromosome's short arm, while in the rest of the cases there
is a transmission from parents. The clinical manifestations of
this syndrome are moderate and nonspecific. In the clinical
research they could be neglected. Its usual manifestations
include: mental retardation in various degree, postnatal
growth restriction, short stature, delayed speech
development, as well as craniofacial malformations. At birth,
the phenotypic manifestations of the syndrome are minimal
and the abnormalities become visible after the age of three.
The final diagnosis requires karyotyping and an analysis of
fetal chromosomes or an analysis of an afflicted person.
Previous research have shown that the critical point for the
breakage located near the centromere in the region 18 p11.1
(it is present in 44% - 72% of examinees). The breakage in
the region between p11.1 and p1.21 is linked to a higher
degree of mental retardation compared to the breakages
distally from these points at the p chromosome's arm. The
examples of prenatally detected monosomy 18p are sporadic
and they are usually found after abnormal ultrasound
findings in the first trimester or accidentally by invasive
prenatal diagnostics. In the cases of monosomy 18 p detected
prenatally or in the cases of giving a birth to a child with this
type of chromosomal aberration, a parents' karyotypes
should be defined with the purpose to provide genetic advice
to the parents.
Key words: chromosomes, human, pair 18; monosomy;
chromosome deletion.
... The most common phenotype of 18p deletion syndrome includes growth retardation, short stature, facial deformity (eg, low nasal bridge, protruding ears), and developmental delay (Babovic-Vuksanovic et al, 2004;Maranda et al, 2006;Portnoi et al, 2007;Thompson et al, 1986;Wester et al, 2006). The phenotypes of individuals with this syndrome vary widely, however, because the expression of characteristics depends on the deletion size and specific breakpoints. ...
... Consistent with previous findings of intellectual impairment in people with 18p deletion syndrome (Babovic-Vuksanovic et al, 2004;Maranda et al, 2006;Portnoi et al, 2007;Thompson et al, 1986;Wester et al, 2006), patient J.K. had borderline intellectual function among his multiple areas of developmental delay. However, he scored in the low average range on the Picture Concepts and Matrix Reasoning test of the Wechsler Preschool and Primary Scale of Intelligence, 3rd ed. ...
We report the neuropsychological profile of a 4-year-old boy with the rare 18p deletion syndrome. We used a battery of standardized tests to assess his development in intellect, language, visuomotor integration, academic readiness, socialization, and emotional and behavioral health. The results showed borderline intellectual function except for low average nonverbal reasoning skills. He had stronger receptive than expressive language skills, although both were well below his age group. He had impaired visuomotor integration and pre-academic skills such as letter identification. Emotional and behavioral findings indicated mild aggressiveness, anxiety, low frustration tolerance, and executive function weaknesses, especially at home. Interestingly, he showed social strengths, responding to joint attention and sharing enjoyment with his examiner. With its assessment of development in many domains, this case report is among the first to characterize the neuropsychological and psychiatric function of a young child with 18p deletion syndrome. We discuss the implications of our findings for clinical practice.
... Its estimated prevalence is 1 in every 50,000 live births and its phenotypic variability makes it difficult to recognize. Female to male ratio is 3:2 [1] and average birth weight is 2600 g. [2] Case Report ...
... [1] Other abnormalities such as blepharoptosis, mid-facial hypoplasia, flat face, hypertelorism, renal hypoplasia, cardiopathy, cebocephaly, dystonia can be observed. [1,2] Nearly 85% of the cases have originated from a de novo deletion and less often from familial origin. [1] Mental retardation varies from mild to severe with IQ between 45 and 50. ...
... [1] Mental retardation varies from mild to severe with IQ between 45 and 50. [2] Growth retardation is associated with growth hormone deficiency and responds well to hormone supplementation. [2] Affected parents can show 18p 11.2 deletion and it has been observed that women transmit unbalanced chromosome aberration more frequently than men, but Schaub et al. concluded equal parental origin of the condition. ...
Deletion of the short arm of chromosome 18 is a rare syndrome clinically presenting with variable mental retardation, growth retardation, low height, pectus excavatum, craniofacial malformations including long ear, ptosis, microcephaly and short neck. This case report presents with characteristic features along with rare feature of single nostril.
... Relevantly , syndrome of monosomy 18p, with deletion of all or part of the short arm of chromosome 18 (Grosso et al. 2005; Turleau 2008), is manifested as short stature, round face with short philtrum, palpebral ptosis, flat nasal bridge, large ears with detached pinnae, and short neck. Mental retardation and speech delay are very frequent, and intellectual deficiency is mild to moderate (Wester et al. 2006; Maranda et al. 2006; Koshy et al. 2011 ). Isochromosome 18q is a rare cytogenetic abnormality usually viewed as Edwards syndrome for its trisomy 18q and the similar features, the clinical characters of which are variable, and overlap with monosomy 18p (Hook et al. 1989; Turan et al. 2005; Pal et al. 2007 ). ...
