Meier-Gorlin Syndrome 4

A number sign (#) is used with this entry because of evidence that Meier-Gorlin syndrome-4 (MGORS4) is caused by homozygous or compound heterozygous mutation in the CDT1 gene (605525) on chromosome 16q24.

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

Feingold (2002) reported 4 patients with Meier-Gorlin syndrome from 2 families. All 4 patients had microcephaly but none had mental retardation, and some were of high intellect. On radiography, all 4 patients had absent or hypoplastic patella, abnormal glenoid fossa, hook-shaped clavicles, and long slender bones. Bicknell et al. (2011) noted that 2 affected sisters from 1 of the families described by Feingold (2002) also displayed mammary gland hypoplasia.

Guernsey et al. (2011) restudied 1 of the patients with Meier-Gorlin syndrome, originally reported by Bongers et al. (2001) ('patient 8'), a 15-year-old girl born of consanguineous parents of Louisiana Cajun ancestry. Feeding was difficult in infancy, and she required a gastrostomy tube until 3 years of age. She had patent ductus arteriosus that required closure with interventional coiling. She had short stature and microtia; her patellae were nonpalpable in childhood but in adolescence were noted to be present but markedly hypoplastic, and she also had genu recurvatum. She developed thoracic scoliosis in the second decade of life that required fusion of the T3 to T12 vertebrae. In childhood she was noted to have hypoplastic labia majora, and at 15 years of age, she had no breast development.

Bicknell et al. (2011) analyzed the candidate gene CDT1 in patients with an established diagnosis of Meier-Gorlin syndrome and identified compound heterozygous mutations (see, e.g., 605525.0001-605525.0004) in 7 patients from 5 families, including 3 sibs from 1 of the families previously described by Feingold (2002).

In a 15-year-old girl with Meier-Gorlin syndrome, previously reported by Bongers et al. (2001), Guernsey et al. (2011) sequenced candidate genes encoding ORC complex or pathway-associated proteins and identified homozygosity for a missense mutation in the CDT1 gene (605525.0005).