вход по аккаунту



код для вставкиСкачать
American Journal of Medical Genetics 85:495–497 (1999)
Brief Clinical Report
Sporadic Case of Trichorhinophalangeal Syndrome
Type III in a European Patient
Catheline Vilain,1 Yves Sznajer,1 Françoise Rypens,2 Daniel Désir,3 and Marc J. Abramowicz1*
Department of Medical Genetics, Brussels University Clinics—Hôpital Erasme, Free University of Brussels (ULB),
Brussels, Belgium
Department of Medical Imaging, Brussels University Clinics—Hôpital Erasme, Free University of Brussels (ULB),
Brussels, Belgium
Department of Endocrinology, Brussels University Clinics—Hôpital Erasme, Free University of Brussels (ULB),
Brussels, Belgium
Trichorhinophalangeal syndrome type III
(TRP III) shares common traits with TRP I
and II, including sparse hair, a “pearshaped” nose, osteodysplasia with coneshaped epiphyses, and autosomal dominant
inheritance, but is distinguished by the
presence of severe brachydactyly. TRP III
was first described in 1984 in Japanese patients, one sporadic case [Sugio and Kajii,
1984: Am. J. Med. Genet. 19:741–753,1984]
and two families [Niikawa and Kamei, 1986:
Am. J. Med. Genet. 24:759–760; Nagaı̈ et al.,
1994: Am. J. Med. Genet. 49:278–280], and
more recently in a Turkish family [Itin et al.,
1996: Dermatology 193:349–352]. We report
an additional observation in a patient of European descent, who presented with short
stature, cone-shaped epiphyses, sparse hair,
a pear-shaped nose, normal intelligence and
severe brachydactyly. Neither parent had
manifestations of TRP and there was no
other reported case in the family, indicating
a presumably fresh mutation. Our observation refines the clinical spectrum of TRP III
in another ethnic background and may be of
help in identifying the gene or genes for
TRP syndromes. Am. J. Med. Genet. 85:495–
497, 1999. © 1999 Wiley-Liss, Inc.
KEY WORDS: brachydactyly; alopecia; osteodysplasia; arthropathy
The trichorhinophalangeal (TRP) syndromes are distinguished as type I, II, and III. TRP I is characterized
C. Vilain and Y. Sznajer contributed equally to this work.
*Correspondence to: Marc J. Abramowicz, M.D., Ph.D., Service
de Génétique médicale, Hôpital Erasme, B-1070 Brussels, Belgium. E-mail:
Received 2 November 1998; Accepted 8 March 1999
© 1999 Wiley-Liss, Inc.
by sparse hair, a distinctive, bulbous nose with dorsally
tented nares, and mild skeletal dysplasia with coneshaped epiphyses, short stature, and shortening of the
metacarpals and metatarsals [Giedion et al., 1973].
TRP II includes findings of TRP I, exostoses, mental
retardation, and skin abnormalities [Hall et al., 1974].
TRP III was first described by Sugio and Kajii in 1984.
It differs from TRP II by normal intelligence and absence of exostoses and from TRP I by the severe shortness of all phalanges and metacarpals. To date, a Japanese TRP III sporadic case [Niikawa and Kamei, 1986],
another Japanese family with four affected individuals
[Nagai et al., 1994], and a Turkish family with seven
patients [Itin et al., 1996] have been reported. TRP III
seems much rarer than the other types. When familial,
inheritance of the TRP syndromes is autosomal dominant, with male-to-male transmission [Itin et al.,
1996]. Cytogenetic observations in TRP I mapped the
defect to 8q24 [Bühler and Malik, 1984] with no evidence for locus heterogeneity [Ludecke et al., 1995].
Although a TRP gene has not been cloned yet, evidence
indicates that TRP type II may be caused by a contiguous gene deletion in the 8q24 region encompassing the
TRP1 and EXT1 loci, defects of the latter causing dominantly inherited multiple exostoses [Ludecke et al.,
We report on an additional case of TRP III, to our
knowledge the first in a patient of western European
A 29-year-old man was investigated for chronic pain
in multiple joints. He was short (147 cm), and had a
distinctive face, with a “pear-shaped” nose and hypoplastic alae nasi (Fig. 1). The hair was sparse with
baldness in rapid progression since a few months before admission. The beard was also sparse. The hands
were extremely short, with a total hand length of 13.5
cm and a middle finger length of 5.7 cm, both values
below the 3rd centile. The hands had a swollen appearance, and the patient was handicapped from pain limiting finger movement. The feet were short, with very
Vilain et al.
Fig. 1. A composite of the patient. Distinctive face with pear-shaped nose and long philtrum, and sparseness of hair and beard. Short, swollen hands
with severe brachydactyly. Short metacarpals and phalanges. The distal epiphysis of the second metacarpal is cone shaped.
short first and fourth metatarsals. The gait was abnormal, with limping and pain in the left hip. The patient
reported a subjective feeling of an accelerated aging
process and was depressed. He was of normal intelligence and worked as a computer operator.
He was born to healthy, nonconsanguineous Belgian
parents, the father being 175 cm and the mother 157
cm tall. A younger sister was 180 cm tall and of normal
appearance, and review of the family history was unremarkable. Birth weight and length had been normal
(3.3 kg and 52 cm). He was first investigated at 3 years
for moderately short stature. Supernumerary teeth
were removed, and bilateral carpal tunnels surgically
X-ray skeletal investigations showed numerous abnormalities including short metacarpals and metatarsals with cone-shaped epiphyses (Fig. 1), Legg-CalvéPerthes–like changes of the femoral epiphyses, mild
scoliosis, and generalized osteopenia. There were no
A standard karyotype was normal and fluorescent in
situ hybridization (FISH) analysis of 8q24 probed with
Y30C3 [Ludecke et al., 1995] detected two normal signals (not shown).
Our patient displays marked growth retardation and
severe brachydactyly along with hair, facial, and epiphyseal changes typical of TRP, with absence of mental
retardation or exostoses, consistent with a diagnosis of
TRP type III [Nagaı̈ et al., 1994]. To our knowledge,
this is the first case of TRP III in a western European
patient. It is a sporadic case, consistent with a new
Severe brachydactyly is the hallmark of TRP III.
However, it is not a constant finding in all affected
subjects from TRP III families [Sugio and Kajii, 1984],
and it has been observed in patients from TRP I families [Giedion et al., 1973]. Thus it remains possible that
the TRP III brachydactyly might represent one phenotypic extreme of the clinical spectrum of TRP I. If TRP
I and III should prove to be allelic disorders, our observation may help delineate genotype-phenotype correlations regarding brachydactyly.
TRP III in a European Patient
Although the TRP genes have not been cloned yet,
evidence suggests that null mutations may cause TRP
I, given that small deletions of the 8q24.12 region have
been observed in TRP I patients, and larger ones encompassing the 8q24.11-8q24.13 region in TRP II patients [Bühler and Malik, 1984; Ludecke et al., 1995].
Marked growth retardation and severe brachydactyly
are not cardinal manifestations of TRP II, a finding
that argues against the presence of a distinct gene
within the contiguous 8q24 segment responsible for severe brachydactyly, and favors the hypothesis of locus
heterogeneity for TRP III. Consistent with this speculation, the 8q24 region appeared intact in our patient
on FISH analysis using probe Y30C3.
Bühler EM, Malik NJ. 1984. The tricho-rhino-phalageal syndromes: Chromosome 8 long arm deletion: is there a shortest region of overlap between reported cases? TRP I and TRP II syndromes: Are they separate
entities? Am J Med Genet 19:113–119.
Giedion A, Burdea M, Fruchter Z, Meloni T, Trosc V. 1973. Autosomaldominant transmission of the tricho-rhino-phalangeal syndrome. Report of 4 unrelated families, review of 60 cases. Helv Paediatr Acta
Hall BD, Langer LO, Giedion A, Smith DW, Cohen MM Jr, Beals RK,
Brandner M. 1974. Langer-Giedion syndrome. Birth Defects 10:147–
Itin PH, Bohn S, Mathys D, Guggenheim R, Richard G. 1996. Trichorhinophalangeal syndrome type III. Dermatology 193:349–352.
Ludecke HJ, Wagner MJ, Nardmann J, La Pillo B, Parrish JE, Willems PJ,
Haan EA, Frydman M Hamers GJH, Wells DE, Horsthemke B. 1995.
Molecular dissection of a contiguous gene syndrome: localization of the
genes involved in the Langer-Giedion syndrome. Hum Mol Genet 4:31–
Nagaı̈ T, Nishimura G, Kasai H, Hasegawa T, Kato R, Ohashi H, Fukushima Y. 1994. Another family with tricho-rhino-phalangeal syndrome
type III (Sugio-Kajii syndrome). Am J Med Genet 49:278–280.
Niikawa N, Kamei T. 1986. The Sugio-Kajii syndrome, proposed trichorhino-phalangeal syndrome type III. Am J Med Genet 24:759–760.
Sugio Y, Kajii T. 1984. Ruvalcaba syndrome: autosomal dominant inheritance. Am J Med Genet 19:741–753.
Без категории
Размер файла
193 Кб
Пожаловаться на содержимое документа