MVA2 is a rare recessive condition presenting with a complex phenotype that includes growth retardation, typically of prenatal onset, distinctive facial features, endocrine, cardiovascular and skeletal abnormalities. This disease is caused by biallelic changes (mutations or pathogenic variants) in the CEP57 gene. The first description of this gene being associated with problems in humans was in 2011. Since then, only a few cases have been recognized affecting males and females.
The medical problems a person with MVA2 will have, can be very variable and difficult to predict. However, there are some common problems that could be observed in affected individuals:
Growth parameters
Marked growth retardation is observed in all cases, in most cases of prenatal origin, being a hallmark of the condition.
Facial dysmorphisms
Facial features have not been systematically assessed. Nevertheless, common manifestations include a triangular face with a prominent forehead and frontal bossing, low set ears and small jaw. Sparse hair is also observed. Small head (microcephaly) is not a constant feature only present in 36% of the cases and even in 25% macrocephaly (big head ) or relative macrocephaly has been observed.
Skeletal abnormalities
Skeletal manifestations have been reported in 66% of the cases. These include shortening of upper or lower extremities or both (58%), short fingers (41%), thumb hypoplasia (25%) and osteolytic lesions (areas of bone destruction) in the skull (16%).
Cardiovascular defects
Congenital heart defects, mainly septal defects (a hole in the wall, septum, that divides the left and right chambers of the heart), have been observed in 50% and vascular malformations in 42%.
Endocrine abnormalities
36% of the patients presented with hypothyroidism (low leves of thyroid hormone). In addition, growth hormone deficiency has been detected in 25% of the cases, without response to GH replacement therapy. No other hormonal deficits have been documented.
Neurological features
Cognitive development was reported to be normal in 40% of the cases or only mildly delayed in 60%.
From the cases where brain imaging was available, abnormalities were detected in 33% of them.
As we identify more children and adults affected by MVA2 we hope to have a better picture of the syndrome and its effects.
CEP57