Meier-Gorlin syndrome.

Sonja A De Munnik,Jolt Roukema,Ernie Mhf Bongers,Nine Vam Knoers,Elisabeth H Hoefsloot,Han G Brunner,Andrew P Jackson,Jeroen Schoots

doi:10.1186/s13023-015-0322-x

Abstract

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females and urogenital anomalies, such as cryptorchidism and hypoplastic labia minora and majora. Typical facial characteristics during childhood comprise a small mouth with full lips and micro-retrognathia. During ageing, a narrow, convex nose becomes more prominent. The diagnosis MGS should be considered in patients with at least two of the three features of the clinical triad of microtia, patellar anomalies, and pre- and postnatal growth retardation. In patients with short stature and/or microtia, the patellae should be assessed with care by ultrasonography before age 6 or radiography thereafter. Mutations in one of five genes (ORC1, ORC4, ORC6, CDT1, and CDC6) of the pre-replication complex, involved in DNA-replication, are detected in approximately 67-78 % of patients with MGS. Patients with ORC1 and ORC4 mutations appear to have the most severe short stature and microcephaly.Management should be directed towards in-depth investigation, treatment and prevention of associated problems, such as growth retardation, feeding problems, hearing loss, luxating patellae, knee pain, gonarthrosis, and possible pulmonary complications due to congenital pulmonary emphysema with or without broncho- or laryngomalacia. Growth hormone treatment is ineffective in most patients with MGS, but may be effective in patients in whom growth continues to decrease after the first year of life (usually growth velocity normalizes after the first year) and with low levels of IGF1. At present, few data is available about reproduction of females with MGS, but the risk of premature labor might be increased.Here, we propose experience-based guidelines for the regular care and treatment of MGS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0322-x) contains supplementary material, which is available to authorized users.

Highlights

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature
The reported percentages of clinical symptoms are calculated from the frequency of these symptoms in the 38 patients with bi-allelic mutations in one of the five causative pre-replication complex genes (ORC1, Origin recognition complex subunit 4 (ORC4), Origin recognition complex subunit 6 (ORC6), Chromatin licensing and DNA replication factor 1 (CDT1), and Cell division cycle 6 (CDC6)) described in literature [1,2,3,4,5]
The diagnosis MGS should be considered in patients with short stature or microtia, and the presence of these features necessitates comprehensive examination of the patellae

Summary

Introduction

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. The diagnosis MGS should be considered in patients with at least two of the three features of the clinical triad of microtia, patellar anomalies, and pre- and postnatal growth retardation. Definition Meier-Gorlin syndrome (MGS) is characterized by the triad of microtia, absent or small patellae and short stature. At least two of these three clinical features are present in 97 % (32/33) of patients with MGS, the combination of patellar a-/hypoplasia and microtia being the most prevalent. The exact prevalence of MGS has not been determined, but is estimated to be less than 1-9/1,000,000 based on the number of cases described in literature This might be an underestimation, due to underreporting and missed diagnoses. The classical triad of clinical features comprises microtia, patellar aplasia or hypoplasia, and pre- and postnatal growth retardation

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Conclusion