Meier‐Gorlin syndrome

Feingold, Murray

doi:10.1002/ajmg.10315

Cited by 7 publications

(6 citation statements)

References 2 publications

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“…[2][3][4][5]8,11,[13][14][15][16][17]21 The remaining 10 individuals were not yet described in literature. These 10 individuals were referred to the Human Genetics departments of the Radboud University Nijmegen Medical Centre, the Netherlands and the Western General Hospital in Edinburgh, UK for molecular analysis from the Netherlands, the UK, Ireland and India.…”

Section: Methods Patientsmentioning

confidence: 99%

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

et al. 2012

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Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were identified in individuals with MGS. Here, we report on genotype-phenotype studies in 45 individuals with MGS (27 females, 18 males; age 3 months-47 years). Thirty-five individuals had biallelic mutations in one of the five causative pre-replication genes. No homozygous or compound heterozygous null mutations were detected. In 10 individuals, no definitive molecular diagnosis was made. The triad of microtia, absent/hypoplastic patellae, and short stature was observed in 82% of individuals with MGS. Additional frequent clinical features were mammary hypoplasia (100%) and abnormal genitalia (42%; predominantly cryptorchidism and hypoplastic labia minora/majora). One individual with ORC1 mutations only had short stature, emphasizing the highly variable clinical spectrum of MGS. Individuals with ORC1 mutations had significantly shorter stature and smaller head circumferences than individuals from other gene categories. Furthermore, compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4 and more frequently pulmonary emphysema in CDT1. A lethal phenotype was seen in four individuals with compound heterozygous ORC1 and CDT1 mutations. No other clear genotype-phenotype association was observed. Growth hormone and estrogen treatment may be of some benefit, respectively, to growth retardation and breast hypoplasia, though further studies in this patient group are needed. (MIM 224690) is a form of primordial dwarfism, characterized by microtia, short stature, and absent or hypoplastic patellae. Furthermore, pulmonary emphysema, feeding problems, various skeletal abnormalities, genitourinary anomalies, and mammary hypoplasia frequently accompany this autosomal recessive disorder. Characteristic facial features, which gradually change with age, are frequently described. Infants typically have a small mouth with full lips and micrognathia, whereas in adults, a high forehead and a more prominent, narrow nose with a broad nasal bridge are distinguishable.The first patient was reported by Meier in 1959. 1 Gorlin reported the second patient with a similar phenotype. 2 In total, only 53 cases have been described in the literature thus far. Recently, mutations in ORC1, a pre-replication complex member gene, were identified in 5 out of 204 individuals with microcephalic primordial dwarfism. 13 As individuals with mutations in ORC1 showed overlapping features with MGS, mutation analysis of ORC1 was performed in 33 individuals with MGS and revealed mutations in 4 individuals from three families. 13 Mutation analysis of other genes of this prereplication complex showed mutations in ORC4, ORC6, CDT1, and CDC6 in 14 individuals fro...

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Section: Methods Patientsmentioning

confidence: 99%

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

et al. 2012

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“…The demographic data of our cohort are summarized in Tables Ia and Ib. All patients were previously described in literature [Gorlin et al, 1975; Cohen et al, 1991; Lacombe et al, 1994; Verhallen et al, 1999; Terhal et al, 2000; Bongers et al, 2001; Feingold, 2002; Shalev and Hall, 2003; Guernsey et al, 2011; Bicknell et al, 2011a, b; de Munnik et al, 2012].…”

Section: Methodsmentioning

confidence: 99%

“…Sixty‐three cases of MGS have been described in literature, thus far [Meier et al, 1959; Gorlin et al, 1975; Hurst et al, 1988; Cohen et al, 1991; Boles et al, 1994; Lacombe et al, 1994; Buebel et al, 1996; Fryns, 1998; Loeys et al, 1999; Verhallen et al, 1999; Terhal et al, 2000; Bongers et al, 2001; Cohen et al, 2002; Feingold, 2002; Shalev and Hall, 2003; Dudkiewicz and Tanzer, 2004; Faqeih et al, 2005; Gezdirici et al, 2010; Guernsey et al, 2011; Bicknell et al, 2011a, b; de Munnik et al, 2012]. Recently, mutations in five different pre‐replication complex genes ( ORC1 , ORC4 , ORC6 , CDT1 , and CDC6 ) were identified in 67% (31/46) of patients with MGS described in literature [Bicknell et al, 2011a, b; Guernsey et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

Meier–Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder

Munnik

Otten

Schoots

et al. 2012

American J of Med Genetics Pt A

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Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of À4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n ¼ 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth.

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“…Ear-patella-short stature syndrome (MGS) has become one of the increasingly recognized disorders and to date, at least cases of 35 patients have been published [Meier et al, 1959;Gorlin et al, 1975;Hurst et al, 1988;Cohen et al, 1991;Boles et al, 1994;Lacombe et al, 1994;Buebel et al, 1996;Teebi and Gorlin, 1997;Fryns, 1998;Loeys et al, 1999;Verhallen et al, 1999;Terhal et al, 2000;Bongers et al, 2001;Cohen et al, 2002;Feingold, 2002;Shalev and Hall, 2003;Dudkiewicz and Tanzer, 2004]. We observed a new patient with a previously unrecognized finding.…”

Section: To the Editormentioning

confidence: 69%

Meier‐Gorlin (ear‐patella‐short stature) syndrome: Growth hormone deficiency and previously unrecognized findings

Faqeih

Sakati

Teebi

2005

American J of Med Genetics Pt A

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Meier‐Gorlin syndrome

Cited by 7 publications

References 2 publications

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

Meier–Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder

Meier‐Gorlin (ear‐patella‐short stature) syndrome: Growth hormone deficiency and previously unrecognized findings

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