IMAGe Association: Additional Clinical Features and Evidence for Recessive Autosomal Inheritance

Abstract

Congenital adrenal hypoplasia (CAH) normally occurs in the neonatal period, with patients presenting with more or less severe salt-wasting syndrome. X-linked CAH has been associated with mutations in the DAX-1 gene, and boys have also been shown to have hypogonadotrophic hypogonadism. Recently, in three unrelated boys, CAH was associated with intrauterine growth retardation (IUGR), metaphyseal dysplasia and genital abnormalities, defining a new association called IMAGe. We now report four additional patients with this association, including the first living female. The four patients belong to two unrelated families (one brother and one sister from each family). These patients have the main clinical characteristics of IMAGe association: IUGR, facial dysmorphy (frontal bossing, broad nasal bridge, low-set ears), short limbs due to metaphyseal dysplasia, and adrenal insufficiency. As these patients are older than the initial three patients, we can also describe additional features: short adult height, normal puberty in boys as well as in the living girl. The boys have hypospadias associated with micropenis. The living girl came to clinical attention at the age of 5 years as a result of a familial survey, and careful questioning revealed that she had been suffering from mild adrenal insufficiency since early childhood. At least one boy has congenital hypotonia due to muscular dystrophy. In conclusion, these four new cases display familial transmission, strongly suggesting Mendelian autosomal recessive inheritance. Adrenal insufficiency may be mild. Hypotonia, described in all the patients, might be related to paucisymptomatic muscular dystrophy, as this condition is clearly heterogeneous varying with regard to severity, associated manifestations and outcome. If this symptom is part of the syndrome, which we cannot assume, it could help to localize the candidate gene.

Anesthetic and Dental Management of a Child With IMAGe Syndrome

“…1,3-6 Hypercalciuria, 1,4 hypercalcemia, 1,4 cleft palate, 7 nephrocalcinosis, 1 failure to thrive, 3,[5][6][7] and sensorineural hearing loss 7 have also been reported in association with this syndrome. The cause of IMAGe syndrome remains unknown, although various genes have been hypothesized to play a role in the syndrome.…”

“…The cause of IMAGe syndrome remains unknown, although various genes have been hypothesized to play a role in the syndrome. Some studies suggest an autosomal recessive mode of inheritance, 4,5 whereas other studies propose inheritance through genomic imprinting of an autosomal gene. 3 Our patient, with a history of intrauterine growth retardation, left hip dysplasia, and bilateral absence of adrenal glands, met the criteria for a diagnosis of IMAGe syndrome.…”

“…Classical facial features of IMAGe syndrome are frontal bossing, a broad nasal bridge, and low set ears. 1,3,4,6 Few patients have also presented with a high-arched palate and craniosynostosis. 1,4 Case reports have also indicated that microcephaly, micrognathia, a high arched palate or cleft palate, and thin lips are also common among patients.…”

“…1,3,4,6 Few patients have also presented with a high-arched palate and craniosynostosis. 1,4 Case reports have also indicated that microcephaly, micrognathia, a high arched palate or cleft palate, and thin lips are also common among patients. 1,[4][5][6]12 Radiographically, patients have often been found to have delayed bone age and maturation.…”

“…1,4 Case reports have also indicated that microcephaly, micrognathia, a high arched palate or cleft palate, and thin lips are also common among patients. 1,[4][5][6]12 Radiographically, patients have often been found to have delayed bone age and maturation. 1,3,4,12 By definition, patients with IMAGe syndrome have intrauterine growth restriction, and several continue to suffer with postnatal growth failure.…”