Coloboma, mental retardation, hypogonadism, and obesity: Critical review of the so-called Biemond syndrome type 2, updated nosology, and delineation of three “new” syndromes

Abstract

Biemond syndrome type 2 (BS2) is classically regarded as a recessively inherited condition (MIM 210350) comprising mental retardation, coloboma, obesity, polydactyly, hypogonadism, hydrocephalus, and facial dysostosis. Clinically, the disorder is closely related to Bardet-Biedl syndrome. Few cases have been reported, most of them before 1970. We present clinical data on three mentally retarded sporadic cases with coloboma, obesity, and hypogenitalism (in two of them), fitting as first glance a diagnosis of BS2. A review documents striking clinical variability among the patients said to have BS2. We propose a new nosology of those cases and delineate several new clinical forms. Purported BS2 cases may be divided into: (1) Bardet-Biedl syndrome with fortuitous coloboma or aniridia, (2) BS2 sensu stricto, a recessively inherited syndrome of sexual infantilism, short stature, coloboma, and preaxial polydactyly without obesity, only known from the original report, (3) a "new" dominantly inherited form of colobomatous microphthalmia occasionally associated with obesity, hypogonadism, and mental retardation, to which our observations belong. (4) cytogenetically proven Rubinstein-Taybi syndrome (one case), (5) an unclassifiable, early lethal familial syndrome resembling Buntinx-Majewski syndrome, and (6) a "new" coloboma-zygodactyly-clefting syndrome. The latter two syndromes may result from chromosomal anomaly.

A review of the literature of Bardet–Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty

“…Our three cases of genetic obesity, associated with hexadactyly and other clinical abnormalities, were diagnosed as familial cases of BBS, thus excluding other forms of genetic obesity characterized by different main features (such as hearing disorders, coloboma, hypotonia, characteristic facies or facial dysostosis, ataxia, spastic paraplegia, etc.) [96–107]. Our patients presented all the well‐recognized features of BBS [4,10–15,25,28], i.e.…”

“…Differential diagnosis is important because certain syndromes, consisting of ocular and/or auditory defects, mental retardation, genitalia hypoplasia, genetic obesity and digital anomalies (with and without ocular impairment from retinal dystrophy), can be misdiagnosed as BBS, from which, in fact, they should be carefully differentiated [28,96–107]. These syndromes related to BBS are presented in Table 3.…”

A Clinical and Genetic Review of Aniridia

“…Bremond-Gignac et al (47) described WAGRO syndrome (WAGR + Obesity); this may be attributed to the deletion of an obesity gene. Aniridia combined with zonular cataract and polydactyly was also explained in a patient with Bardet-Biedl syndrome by Verloes et al (48). Electroretinograms (ERGs) performed by Tremblay et al (49) for patients with aniridia, revealed definite retinal dysfunction, although its etiology is not yet clear.…”

Latent common genetic components of obesity traits

“…The dominant model assumes the effects of the two disease-allele carrying genotypes AA and AB are the same (AA = AB) and different from that of the BB genotype. An example is the coloboma-obesity-hypogenitalism-mental retardation syndrome 45. In the recessive model, the genotypic effects of BB and AB are assumed to be the same and different from that of the AA genotype.…”