title: Untreated growth hormone deficiency with extremely short stature, bone dysplasia, cleft lip--palate and severe mental retardation in a 26-year-old man with a de novo unbalanced translocation t(1;12)(q24;q24).
abstract: We report on a 26-year-old patient presenting with extremely short stature (height 72cm, weight 6.5kg, OFC 42.5cm), facial dysmorphism, cleft lip--palate, severe mental retardation and de novo 1q24.2--q25.2 and 12q24.31 interstitial deletion. He was the only child of non-consanguineous parents and his birth length was 43cm. He had severe feeding difficulties and required enteral nutrition until the age of 3 years. Standard cytogenetic analysis showed an apparently balanced de novo translocation t(1;12)(q24;q24). Endocrine studies at 11 years of age for severe growth retardation revealed multiple pituitary hormone deficiency with severe growth hormone deficiency, but the child was untreated because of associated mental retardation. At 26 years of age, he could not walk or speak and had no signs of puberty. Investigations revealed spondylo-epi-metaphyseal dysplasia with severe osteoporosis, enlarged aorta when compared to the patient's size and apparently normal pituitary development. High resolution karyotype showed a 1q24-q25 deletion, and comparative genomic hybridization studies confirmed the 1q interstitial deletion. FISH studies of both breakpoints using PACs and BACs enabled us to further characterize the 1q interstitial deletion (1q24.2-1q25.2) and also revealed a 12q24.31 interstitial microdeletion. This case is compared with previously reported patients with similar deletions, but the untreated pituitary deficiency could also be responsible in part for the severity of the growth deficiency. This observation is of interest for two reasons. First, these deletions could be a clue in the search for a gene responsible for growth hormone deficiency/midline defects. Second, it shows the importance of molecular cytogenetics in the study of de novo apparently balanced translocation with abnormal phenotype.
authors.affiliation: Laboratoire de Cytogénétique, Département de Génétique, CHU Le Bocage, 2 Bd Maréchal de Lattre de Tassigny, 21034 Dijon cédex, France. patrick.callier@chu-dijon.fr
authors.forename: P
authors.initials: P
authors.lastname: Callier
authors.forename: L
authors.initials: L
authors.lastname: Faivre
authors.forename: N
authors.initials: N
authors.lastname: Marle
authors.forename: C
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: A L
authors.initials: AL
authors.lastname: Mosca
authors.forename: A
authors.initials: A
authors.lastname: Masurel-Paulet
authors.forename: J
authors.initials: J
authors.lastname: Borgnon
authors.forename: S
authors.initials: S
authors.lastname: Falcon-Eicher
authors.forename: A
authors.initials: A
authors.lastname: Danino
authors.forename: G
authors.initials: G
authors.lastname: Malka
authors.forename: M
authors.initials: M
authors.lastname: Le Merrer
authors.forename: F
authors.initials: F
authors.lastname: Huet
authors.forename: F
authors.initials: F
authors.lastname: Mugneret
mesh_terms: D000328:Adult; D001848:Bone Diseases, Developmental / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics*; D013006:Growth Hormone / Q000172:deficiency*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D013006:Growth Hormone