Meier-Gorlin Syndrome 8

A number sign (#) is used with this entry because of evidence that Meier-Gorlin syndrome-8 (MGORS8) is caused by compound heterozygous mutation in the MCM5 gene (602696) on chromosome 22q12. One such patient has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of Meier-Gorlin syndrome, see 224690.

Clinical Features

Vetro et al. (2017) studied a 4.75-year-old Italian boy who exhibited intrauterine and postnatal growth restriction, as well as dysmorphic features including microstomia, thick lips, micrognathia, and bilateral low-set small ears. He also had bilateral cryptorchidism, and abdominal ultrasound revealed hypoplasia and ptosis of the left kidney. Psychomotor development and brain NMR were normal. Growth hormone levels were normal, and immunologic evaluation showed normal populations of T and NK cells. Bilateral absence of the ossification centers of the patella was noted at age 20 months, at which time a clinical diagnosis of Meier-Gorlin syndrome was made. At 4.75 years of age, his height and weight were -2.7 SD and -2.5 SD, respectively, and his head circumference was 51 cm (0.3 SD).

Molecular Genetics

By whole-exome sequencing in a 4.75-year-old Italian boy with Meier-Gorlin syndrome, Vetro et al. (2017) excluded mutation in known MGORS-associated genes and identified compound heterozygosity for a 2-bp deletion (602696.0001) and a missense mutation (602696.0002) in the MCM5 gene. The authors stated that the pathogenetic mechanism of MGORS appeared to be impairment of DNA replication initiation because all reported MGORS-associated genes were involved with this pathway.