Growth parameters
Marked growth retardation, in most cases of prenatal origin, is observed in all cases, being a hallmark of the condition.
Facial dysmorphism
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 micrognathia. Sparse hair is also observed. Microcephaly is not a constant feature only present in 36% of the cases and even in 25% macrocephaly or relative macrocephaly has been observed.
Skeletal abnormalities
Skeletal manifestations have been reported in 66% of the cases. These include rhizomelic shortening of upper or lower extremities or both (58%), brachydactyly (41%), thumb hypoplasia (25%) and osteolytic lesions in the skull (16%). These data suggest a possible disturbance of bone metabolism.
Cardiovascular defects
Congenital heart defects, mainly septal defects, have been observed in 50% and vascular malformations in 42%. Most patients had a cardiac MRI allowing the identification of malformations in the great vessels, but very few had a specific study to identify vascular malformations elsewhere. In the only two patients in which abdominal CT studies were performed, vascular malformations, in addition to those described in the great vessels, were identified. In any case, further evaluation of additional patients to detect vascular malformations is required to assess if this is a true association or a coincidental finding and the need for routine evaluation of possible vascular malformations in this group of patients.
Endocrine abnormalities
36% of the patients presented with hypothyroidism. In addition, GH 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 (10), abnormalities were detected in 33% of them. These abnormalities included pituitary atrophy/hypoplasia (22%), widened cerebral subarachnoid space (11%), enlarged interhemispheric fissure (11%), hydrocephalus (11%) and thin corpus callosum (11%).
CEP57