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Facial features, small triangle face, long peaked nose, high nasal bridge, micrognathia and microstomia.
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We report a 7 year old female child with the classical triad of Meier-Gorlin syndrome (MGS), (microtia, absent patella and short stature). She had the characteristic facial features, with normal mentality and defective speech, skeletal abnormalities, conductive hearing loss, cystitis and normal growth hormone level. She suffered from recurrent ches...
Citations
... In 97% of patients, two out of three findings are seen. The most common findings include patellar hypoplasia and microtia (1,10). However, it is worth noting that MGS clinical phenotype might be varied to the extent that short stature can be the only manifestation of MGS (2). ...
... Although Seckel syndrome is one of the important differential diagnoses in short stature, its height and head circumference are much smaller than MGS. Other syndromes such as Russell-Silver, Majewski osteodysplasia-tic bird-head dwarfism type I/II/III, Rapidilinio, nail patella, and Coffin-Siris can mimic MGS signs as well (10,11). It is noteworthy that nail dysplasia is absent in MGS, which can differentiate it from nailpatella syndrome (9). ...
Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder with homozygous or heterozygous mutations in one of the five following genes (ORC1, ORC4, ORC6, CDT1, and CDC6). This syndrome is characterized by the triad of short stature (pre/postnatal), microtia, and patella hypoplasia/aplasia. Special features included microcephaly, microstomia, full lips, micrognathia, narrow convex, and high nasal bridge nose. Also, it may be accompanied by feeding problems, skeletal disorders, urogenital or respiratory anomalies, and intelligence disorders. This case report describes the first Persian MGS accompanied by neonatal seizure, mental retardation, and attention deficit hyperactivity disorder.
... As yet, patients with ORC1 mutation have not shown any improvement to growth hormone (GH) therapy. Therefore, unknown underlying molecular defects were deemed to cause global growth retardation rather than GH deficiency [7] . However, the hypothesis is not confirmed by molecular studies and there is a doubt about the gene effects. ...
... Of all the confirmed MGS patients that have been previously reported, the MGS1 subtype was never along with any improvement to GH therapy. Thus, understanding the exact underlying molecular defects and their mechanism contributing to patients' phenomenon is essential for developing novel therapeutic targets and options [7] . ...
Meire-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by a triad of short stature, microtia, and absent or hypoplastic patella. We report a 5-year-old male affected with the subtype MGS1, secondary to c.c2292t mutation of ORC1 gene. Our patient's features included a triangular face, micrognathia, and delayed motor development. To the edge of our knowledge, this is the first diagnosed Iranian MGS patient and sixth case in the middle east. MGS1 subtype has never shown improvement to growth hormone therapy, therefore underlying molecular defect was suggested to be responsible for patients’ short stature rather than growth hormone deficiency. However, our patients’ growth velocity was improved by growth hormone. We recommend more studies to specify the role of ORC1 gene in this syndrome. In addition, this case report describes the prenatal investigations and sonographic examinations of MGS1 for the first time.
... Three cases of cardiovascular involvement have been described. 1,2 Intelligence is usually preserved, but motor and/or language development is delayed. 1,[3][4][5][6] Meier-Gorlin syndrome is a genetically heterogeneous disease. ...
Background:
Meier-Gorlin syndrome (MGS) is a rare genetic syndrome inherited in an autosomal dominant or autosomal recessive manner. The disorder is characterized by bilateral microtia, absence or hypoplasia of the patella, and an intrauterine growth retardation as well as a number of other characteristic features. The cause of the disease is mutations in genes encoding proteins involved in the regulation of the cell cycle (ORC1, ORC4, ORC6, CDT1, CDC6, GMNN, CDC45L, MCM3, MCM5, MCM7, GINS2, and DONSON). Meier-Gorlin syndrome 5 due to mutations in the CDC6 gene is difficult to diagnose, and few clinical data have been described to date. Only one patient (male) with a missense mutation in a homozygous state has been previously reported. This report describes a new clinical case of Meier-Gorlin syndrome 5. This is also the first report of a Russian patient with Meier-Gorlin syndrome.
Case presentation:
The patient, a female, had extremely low physical development, neonatal progeroid appearance, lipodystrophy, thin skin, partial alopecia, cyanosis of the face, triangular face, microgenia, arachnodactyly, delayed bone age, hepatomegaly, hypoplasia of the labia majora, and hypertrophy of the clitoris in addition to known clinical signs. Differential diagnosis was performed with chromosomal abnormalities and Hutchinson-Gilford progeria. According to the results of sequencing of the clinical exome, the patient had two previously undescribed variants in the CDC6 gene, c.230A>G (p.(Lys77Arg)) and c.232C>T (p.(Gln78Ter)), NM_001254.3, in a compound heterozygous state.
Conclusion:
This case allows us to learn more about the clinical features and nature of MGS 5 and improve the speed of diagnostics and quality of genetic counseling for such families.
... Patients with MGS may present with variable features, and the classical triad of features (short stature, microtia and patella aplasia/hy poplasia) was found to be present in 82% of patients with MGS (Shawky et al., 2014). In fact, our patient only had short stature. ...
... A study on 45 patients with MGS showed that postnatal growth was delayed during the first year of life, and growth velocity was normal thereafter, hence these patients do not have significant catch-up growth (de Munnik et al., 2015). ORC1 mutations were found to cause the most severe growth failure and microcephaly, followed by ORC4 mutations (Shawky et al., 2014). Our patient's growth trend is illustrated in Fig. 1. ...
... The role of growth hormone in patients with MGS is equivocal. Patients with MGS can have suboptimal or even elevated growth hormone levels, thus suggesting that the short stature is due to the underlying molecular defect rather than growth hormone deficiency (Shawky et al., 2014). As such, growth hormone treatment may not always be useful, especially in those patients with a known mutation. ...
Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CD-C45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynos-tosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.
... The diagnosis of MGS should be considered in patients with at least two of the three features of this clinical triad (De Munnik et al., 2015). In fact, only 82% of the reported cases had the three classical features of MGS explaining the wider variety of phenotypes in MGS than previously expected (De Munnik et al., 2012;Shawky et al., 2014). The association of patellar aplasia/hypoplasia and microtia was the most prevalent (De Munnik et al., 2012;Morankar et al., 2018). ...
... Less common phenotypes reported in MGS but not found in our patient include papilledema, strabismus, bifid uvula, cleft palate, and genu recurvatum (De Munnik et al., 2012;Kalappanavar et al., 2013;Shawky and Gamal, 2016). Cardiovascular defects, brain malformations, and pulmonary emphysema were also described in children with MGS (De Munnik et al., 2012;Shawky et al., 2014). Moreover, the personality of patients with MGS is usually described as cheerful and friendly as detected in our patient (Shalev and Hall, 2003). ...
... Mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6) were identified in individuals with MGS[3]. Here we report the second Egyptian patient with MGS in the same hospital[4]after taking consent of the parents. ...
... Our patient had normal hearing. However our reported 1st case had bilateral moderate conductive hearing loss[4]. Papilledema was reported in MGS. ...
... Echo cardiography of our patient was normal. The 1st reported MGS case in our locality had fenestrated interatrial septum at foramen ovale with minimal shunting[4]. Parental consanguinity and the occurrence of affected sibs of normal parents indicate autosomal recessive inheritance of MGS[14]. ...
We report a 4.5 year old female child with the classical triad of Meier–Gorlin syndrome (microtia, absent patella and short stature) with normal mentality. She had small triangular face, long peaked nose, high nasal bridge, bilateral low set very small ears (microtia), retromicrognathia, high arched palate, maxillary hypoplasia, decayed teeth, and bilateral partial syndactyly between 2nd and 3rd toes. Our patient had a gastroesophageal reflux, renal stones, hydronephrosis and hypoplastic labia majora and minora with clitromegaly.
Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.
