The 6p subtelomere deletion syndrome

Abstract

Submicroscopic deletion of the 6p25 subtelomere has recently been recognized as a clinically identifiable syndrome. To date, more than 30 cases have been described with variable cytogenetically visible 6p deletions. Terminal 6p deletions result in a clinically distinguishable phenotype. The focus of this review is the phenotype associated with isolated terminal deletions of 6p25, and specifically isolated submiscroscopic subtelomere deletions. A distinct phenotype has emerged consisting of developmental delay/mental retardation, language impairment, hearing loss, and ophthalmologic, cardiac, and craniofacial abnormalities. These features demonstrate considerable clinical overlap with the Ritscher-Schinzel (or cranio-cerebello-cardiac (3C)) syndrome (OMIM #220210). Isolated submiscroscopic 6p25 subtelomere terminal deletion has been reported in 11 individuals, two of whom are siblings. Cytogentic and molecular mapping of the 6p25 deletion boundary has been reported in 8 of these 10 unrelated individuals with isolated submiscroscopic subtelomere deletion. This analysis has revealed substantial phenotypic overlap between individuals with submicroscopic terminal 6p deletions and those with large, cytogenetically visible deletions of the region suggesting that the critical genes contributing to the main clinical and developmental features lie in the terminal region of 6p25.

The 6p25 deletion syndrome: An update on a rare neurocristopathy

“…Unlike interstitial deletions with breakpoints in the 6p22-6p24 region excluding FOXC1, both interstitial and terminal deletions with breakpoint(s) in the 6p24-pter region encompassing FOXC1 result in a typical ARS-like phenotype referred to as the 6p25 deletion syndrome. [13][14][15]28 In cases where the distal 6p deletion encompassing FOXC1 is not isolated but part of an unbalanced translocation, the associated reciprocal duplication can extend this phenotype with unique features. In the next section the phenotype of the 6p25 deletion syndrome is illustrated by a single case, after which an overview of clinical features described in the literature is provided.…”

PITX2 and FOXC1 spectrum of mutations in ocular syndromes

“…De Hauwere syndrome (OMIM: 109120), characterized by anterior segment eye defects, hypertelorism, psychomotor retardation, hypotonia, hearing loss, hydrocephalus/enlarged ventricles, and femoral head anomalies, 21,22 displays a significant overlap with 6p25 deletion syndrome (OMIM: 612582), defined as a combination of ocular anomalies (primarily anterior segment), hearing loss, congenital heart disease, hydrocephalus, developmental delay, and a characteristic facial appearance and typically associated with terminal deletions of 6p25. 32,33 Review of the literature identified that the skeletal features observed in De Hauwere syndrome, such as flattening of the femoral epiphyses and other femoral head anomalies sometimes diagnosed as Perthes disease, were reported in several previously described patients with 6p25 terminal deletions (Table 3), 32,[34][35][36][37][38] suggesting that De Hauwere syndrome may be part of the 6p25 deletion syndrome spectrum. Case 28 in our study has the smallest and first interstitial deletion reported to date in association with the features of De Hauwere syndrome, thus defining a minimal deleted region for this phenotype.…”

Trypanosoma brucei TIF2 suppresses VSG switching by maintaining subtelomere integrity

“…Drastically reduced D4Z4 repeat number can lead to abnormal DUX4 transcription and is associated with facioscapulohumeral muscular dystrophy (FSHD) [2]. Submicroscopic deletion of subtelomeric 6p25 and 9q has been recognized as clinically identifiable syndromes [3,4]. In addition, some OR genes encoding olfactory receptors are located at subtelomeres, and changes in subtelomeres contribute to the diversity of the OR gene family [5].…”