medwireNews: Researchers describe a novel autosomal recessive genetic syndrome that may be misdiagnosed as Prader–Willi syndrome (PWS).
Their publication describes four patients from three unrelated consanguineous families, bringing the total number of cases reported to date to eight. The condition has been termed Blakemore–Durmaz–Vasileiou (BDV) syndrome, after the senior authors of these reports.
The authors of the latest publication, Georgia Vasileiou (Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany) and colleagues, say that all eight reported cases had a neurodevelopmental disorder with moderate intellectual disability, severe speech delay and mild or moderate motor delay. In addition, seven had severe or very severe obesity, and six cases with available information had hyperphagia and five had infantile hypotonia.
“Given the overlapping clinical presentation, PWS is an important differential diagnosis”, write Vasileiou and team in The Journal of Clinical Endocrinology & Metabolism.
“Thus, it is not surprising that this was the initially suspected diagnosis in all cases.”
They note: “The absence of short stature and growth hormone deficiency in BDV syndrome could serve as a differentiation parameter, however, not all PWS patients develop short stature and for many of them it is only evident after the second decade.”
Other disorders in the patients with BDV syndrome included hypogonadotropic hypogonadism (diagnosed in four cases and suspected in a further two), insulin resistance, enuresis, hepatic steatosis and hypermetropia. There were also some pubertal abnormalities, including cryptorchidism, hypogenitalism, and amenorrhoea or irregular menstruation.
The team’s four cases underwent genetic testing that excluded PWS; instead, it uncovered mutations in CPE, the gene encoding carboxypeptidase E, as reported in the previously published cases. All the mutations were truncating variants, predicted to produce a shortened version of the protein.
Together, these eight cases from five unrelated consanguineous families, “provide sufficient evidence to confirm a new genetic entity”, the researchers believe.
The eight cases shared some facial characteristics, such as an oval face, coarse features, low-hanging columella (the bridge of tissue that divides the nostrils at the base of the nose), thin upper lip vermilion, everted lower lip vermilion and micrognathia.
In addition, the authors of the current report describe abnormal features including periorbital fullness, wide nasal bridge, tapering fingers, brachydactyly and pes planus.
They note, however, that the anatomical characteristics associated with the syndrome were “less well recognisable” than the neurodevelopmental and bodyweight features.
By Eleanor McDermid
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J Clin Endocrinol Metab 2021; doi:10.1210/clinem/dgab592