Familial occurrence of the IMAGe association: additional clinical variants and a proposed mode of inheritance

BERGADÁ I; DEL REY G; LAPUNZINA P; BERGADÁ C; FELLOUS M; COPELLI S

JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

ENDOCRINE SOC

Lugar: Chevy Chase; Año: 2005

0021-972X

The IMAGe (intrauterine growth retardation, metaphyseal dysplasia,adrenal hypoplasia congenita, genital anomalies) association (onlineinheritance in man 300290) is a recently reported disorder comprisingintrauterine growth retardation (IUGR), metaphyseal dysplasia, adrenalhypoplasia, and genital anomalies. Four children (three males,one female) from a large pedigree (five generations) were studied.Additional members (n 10), who died during the neonatal period,were born with IUGR and/or hyperpigmentation and are presumed tohave been affected, too. All patients in this series were diagnosedduring the newborn period. Minimal clinical features and laboratoryfindings differ with previously reported patients, suggesting variantsin their clinical expression. Adrenal insufficiency was variable withinpatients. All had severe IUGR and marked postnatal growth failure.Sequence analysis of DNA using an automated cycle from two patientsrevealed no mutation in the dosage-sensitive sex reversaladrenalhypoplasia congenita critical region on the X chromosome,gene 1. Analysis of the pedigree showed that the disease is inheritedvia the maternal line, even in the dead children with suspicion of thedisease. Hence, the pattern of inheritance in this family of this unusualdisorder might be explained in terms of the genomic imprintinghypothesis with expression through maternal transmission involvingan autosomal gene. This transmission may have considerable implicationsfor genetic counseling. Furthermore, pediatric endocrinologistsmust be aware of the possible occurrence of this life-threateningcondition in the offspring of nonaffected women when related to afamily member with the association of IUGR, metaphyseal dysplasia,adrenal hypoplasia congenita, genital anomalies