Monday 1 October 2012

17q24.2-q24.3 MICRODELETION SYNDROME (GENERALIZED HYPERTRICHOSIS TERMINALIS, WITH OR WITHOUT GINGIVAL HYPERPLASIA)



The ensemble of extreme hirsutism with gingival fibromatosis was originally described as a dominant trait. Hypertrichosis may be present at birth but often appears at puberty. The entity was later on defined as generalized hypertrichosis terminalis with or without gingival hyperplasia (OMIM 135400). It has been found to be a contiguous gene syndrome caused by microdeletions within the chromosomal region 17q24.2-q24.3.
Far in the 1857, Laurence described a bearded and hairy female. Exhibited as a phenomenon, the young Mexican girl was referred to as 'clothed with hairs' over her entire body except for the palms and the soles. Hair was black and fine, and not curling. Intellect was not reported as affected, rather the girl was reffered to as being “quick”.
We have to wait up to the 1971 for a second report on the syndrome, when Witkop described 52 cases of gingival fibromatosis with hypertrichosis, noting an association with epilepsy and mental retardation.
In 2009, Sun et al. detected genomic microdeletions of different sizes on chromosome 17q24.2-q24.3 as being the cause of the syndrome. The minimal overlapping genomic region in the studied families contained four genes: ABCA5, ABCA6, ABCA10, and MAP2K6. Sun et al. suggested that MAP2K6 was the leading candidate gene from the overlapping region in their patients.
In 2008, Blyth M et al reported about another 2.3Mb deletion of 17q24.2-q24.3 that was associated with Carney complex plus. The most characteristic features in this case were posterior laryngeal cleft and the presence of numerous freckles and lentigines in childhood. Growth restriction, microcephaly and moderate mental retardation were also observed. The authors pointed out that the microdeletion caused haploinsufficiency of the PRKAR1A gene.
In 2012 Lestner JM et al reported about a girl with a 2.3 Mb de novo deletion in chromosome 17q24.2-q24.3, whose phenotype included also skeletal malformations (lower limb bowing, progressive scoliosis and dental abnormalities), feeding problems, mild learning difficulties, and a characteristic facies. They stated that the phenotype is attributable to the deletion of KCNJ2, which causes Andersen Tawil Syndrome.

References: see text.