Long‐term follow‐up of four patients with langer–giedion syndrome: Clinical course and complications

Abstract

Long-term observations of individuals with the so-called Langer-Giedion (LGS) or tricho-rhino-phalangeal type II (TRPS2) are scarce. We report here a on follow-up of four LGS individuals, including one first described by Andres Giedion in 1969, and review the sparse publications on adults with this syndrome which comprises ectodermal dysplasia, multiple cone-shaped epiphyses prior to puberty, multiple cartilaginous exostoses, and mostly mild intellectual impairment. LGS is caused by deletion of the chromosomal segment 8q24.11-q24.13 containing among others the genes EXT1 and TRPS1. Most patients with TRPS2 are only borderline or mildly cognitively delayed, and few are of normal intelligence. Their practical skills are better than their intellectual capability, and, for this reason and because of their low self-esteem, they are often underestimated. Some patients develop seizures at variable age. Osteomas on processes of cervical vertebrae may cause pressure on cervical nerves or dissection of cerebral arteries. Joint stiffness is observed during childhood and changes later to joint laxity causing instability and proneness to trauma. Perthes disease is not rare. Almost all males become bald at or soon after puberty, and some develop (pseudo) gynecomastia. Growth hormone deficiency was found in a few patients, TSH deficiency so far only in one. Puberty and fertility are diminished, and no instance of transmission of the deletion from a non-mosaic parent to a child has been observed so far. Several affected females had vaginal atresia with consequent hydrometrocolpos.

Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome

“…The developmental delay in TRPS II does not correlate with the size of the deleted segment in the present study group, as has been reported before [Schinzel et al, 2013].…”

“…It is well known that TRPS can vary within families, even between MZ twins [Giedion et al, 1973;Naselli et al, 1998;Schinzel et al, 2013]. In the present series there are several families with multiple affected family members in whom this variability is mirrored (Fig.…”

“…We present the results of studies in 103 patients including ninety-six patients that have not been published before, and seven that have been published [Rocha Carvalho et al, 2011;Schinzel et al, 2013;Chen et al, 2013;Plaza-Benhumea et al, 2014]. The clinical data are presented in Tables I-IV and illustrated in Figs.…”

“…The genotype was obtained either from literature if patients had been published [Rocha Carvalho et al, 2011;Schinzel et al, 2013;Chen et al, 2013;Plaza-Benhumea et al, 2014], or the referring clinician. In the majority of patients, DNA had been analysed at the University Hospital in Essen, Germany (HJL).…”

“…The study by Lüdecke and co-workers on 51 unrelated TRPS patients in which they were able to detect 35 different mutations in 44 patients is the most informative one [Lüdecke et al, 2001]. A recent review of the (sparse) literature on adults with this syndrome, including one of the first patients described by Giedion, is also very useful [Schinzel et al, 2013]. Here we report on a series of 103 individuals with TRPS gathered through an international collaborative study.…”