Mulchandani-Bhoj-Conlin Syndrome

A number sign (#) is used with this entry because Mulchandani-Bhoj-Conlin syndrome (MBCS) is an imprinting disorder involving genes within the imprinted region of chromosome 20.

Description

The Mulchandani-Bhoj-Conlin syndrome is characterized by prenatal growth restriction, severe short stature with proportional head circumference, and profound feeding difficulty (Mulchandani et al., 2016).

Clinical Features

Mulchandani et al. (2016) reported 8 patients with intrauterine growth restriction and postnatal failure to thrive. All 8 patients had severe short stature with proportional head circumference and profound feeding difficulties. Age at last evaluation for the 8 patients ranged from 3 months to 12 years. Four patients had mild facial dysmorphism, including one each with epicanthal folds, triangular face with posteriorly rotated ears, and dolichocephaly with retrognathia. Four had hypotonia, which caused motor delay in 2. Five patients had skeletal anomalies: one each with scoliosis, hyperlordosis, or bifid toe, and 2 with clinodactyly of whom 1 also had mild 2-3 toe syndactyly. The patient with the bifid toe also had a horseshoe kidney. Six patients required gastric feeds for some interval in the first 5 years of life. Four were treated with growth hormone with improved linear growth acceleration and no ill effects. Three had pigmentary changes described as 'hyperpigmented spots,' 'irregular pigment,' and 'a cafe-au-lait macule.' Two patients had initially been diagnosed with Silver-Russell syndrome (180860). Maternal age at the patients' birth ranged from 37 to 43 years.

Molecular Genetics

By SNP array, Mulchandani et al. (2016) demonstrated that 4 of the 8 patients they reported had maternal isodisomy, 2 had maternal heterodisomy, and 2 had evidence of 2 cell lines showing both maternal isodisomy and heterodisomy. This supported a chromosome 20 trisomy rescue occurring after meiosis II, consistent with the advanced maternal age of each proband's mother.