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Demirhan sydrome, a new sydrome: Fibular agenesis, cleft palate, absence of multiple permanent teeth and labial hypoplasia


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Background: There are some syndromes described in the literature with agenesis of fibulae and tibia, but to the best of our knowledge, our case is the first one defined with fibular agenesis, and tibial bowing without involvement of femur or upper extremity deformities and teeth abnormalities. Case Report: We report a twelve years old girl, who had severe growth retardation, major lower extremity abnormalities, torticollis, flat face, hypertelorism, thin upper lip, displaced teeth, cleft palate, and labial hypoplasia. Chromosome analysis was performed. Her karyotype was normal female (46,XX) and no chromosomal abnormality was detected. Conclusions: The clinical findings of this case is not in accordance with any known syndrome. It is a new syndrome according to our opinion.
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Demirhan sydrome, a new sydrome: Fibular agenesis,
cleft palate, absence of multiple permanent teeth and
labial hypoplasia
Osman Demirhan1, Neslihan Önenli Mungan2, Serdar Toroğlu3, Figen Binokay4,
Deniz Taştemir1, Hüseyin A. Solğun2
1 Department of Medical Biology and Genetics, Çukurova University, Adana, Turkey
2 Department of Pediatrics, Faculty of Medicine, Çukurova University, Adana, Turkey
3 Department of Orthodontics, Faculty of Dentistry, Çukurova University, Adana, Turkey
4 Department of Radiodiagnostics, Faculty of Medicine, Çukurova University, Adana, Turkey
There are some syndromes described in the literature with agenesis of fi bulae and tibia, but to the
best of our knowledge, our case is the fi rst one defi ned with fi bular agenesis, and tibial bowing
without involvement of femur or upper extremity deformities and teeth abnormalities.
Case Report:
We report a twelve years old girl, who had severe growth retardation, major lower extremity abnor-
malities, torticollis, fl at face, hypertelorism, thin upper lip, displaced teeth, cleft palate, and labial
hypoplasia. Chromosome analysis was performed. Her karyotype was normal female (46,XX) and
no chromosomal abnormality was detected.
The clinical fi ndings of this case is not in accordance with any known syndrome. It is a new syn-
drome according to our opinion.
key words: bular agenesis • cleft palate • absence of multiple permanent teeth • labial hypoplasia •
Full-text PDF:
Word count: 147 8
Figures: 4
References: 13
Author’s address: Osman Demirhan, University of Çukurova, Faculty of Medicine, Department of Medical Biology and Genetics,
01330 Balcali, Adana, Turkey, e-mail:
Received: 2008.04.14
Accepted: 2008.08.19
Published: 2008.08.29
Case Report
© The American Journal of Case Report, 2008; 9: 359-363
Fibular agenesis has been described with digital abnormali-
ties and bowed tibia in Fuhrmann syndrome. Facial dysmor-
phia, mental retardation, and brachydactyly with short-limb
dwarfi sm are the features of one form of this syndrome, al-
though fi bular hypoplasia, proximal focal defi ciency, and
upper extremity deformities with normal intelligence are
the features of the other forms [1–6]. There are some oth-
er syndromes described in the literature with agenesis of
bulae and tibia [1–4,6–8]. Except bilateral agenesis of fi b-
ulae examined in our patient; other characteristic features
do not match with these syndromes. In addition to fi bular
agenesis, torticollis which isn’t due to labour trauma, dis-
placed teeth, hypoplastic labia major, dislocated tibiofemo-
ral and tibiotalar joints, rounded lower thoracal and lumbar
vertebral bodies are the different features of our patient that
lead us to the diagnosis of an undefi ned new syndrome. In
this paper, we present both the clinical and the cytogenetic
ndings of a family with unidentifi ed syndrome.
AKB, 12 years-old girl, was admitted to our hospital with com-
plaints of growth retardation and limb abnormalities. She was
born at the 27 weeks of gestation by normal delivery with feet
presentation. Birth weight was 1500 gr but birth length was
not recorded. The mother had normal a pregnancy. There
was no history of infectious disease, X-ray, alcohol, drugs or
cigarette usage during pregnancy. There was no consanguini-
ty between parents. The patient had a 10 years old healthy sis-
ter. Her mother had a 24 weeks pregnancy on the admission.
Family history revealed no similar abnormalities, congenital
malformations, and inherited or a systemic disease.
On physical examination, the patient had a syndromic facial
appearance and a normal mandibula with a decreased lower
facial height and retrusive maxilla. She had also bowed tib-
ias, and severe foot digities abnormalities (Figure 1). Body
temperature was 36.5°C, pulse rate was 80/min, and arterial
tension was 110/70 mmHg. Weight and height were 24.5 kg
(below 5
percentile) and 93 cm (below 5
percentile), re-
spectively. Her general condition was well. She had fl at nose,
hypertelorism, thin upper lip, displaced teeth, an operated
high cleft palate, and torticollis. Cardiovascular, respirato-
ry and abdominal examination revealed no abnormal fi nd-
ings. She had no neurological abnormalities. Her mental
and motor development was appropriate for her age. She
was seen extremely short due to the very short lower limbs.
She was walking with the help of her mother. Upper limbs
were normal. She had Tanner stage II axillary hair, but no
pubic hair or breast development. She had hypoplasic la-
bia major, but a normal vagen.
Laboratory examination: her blood count and whole blood
biochemistry were in normal limits. She had also a normal
hormone profi le.
During intraoral evaluation (Figures 2A,B); multiple per-
manent teeth were seem to be missed. A panoramic radio-
graph of the patient also revealed the absence of multiple
permanent teeth. These teeth were maxillary right and left
second premolars, maxillary right fi rst premolar, and man-
dibular right and left second premolars. Her maxillary right
lateral incisor and mandibular left central incisor had ab-
normal tooth shape (small and cone-shaped). Dental mid-
lines were coincident (Figure 2A). The mandibular left pri-
mary second molar teeth was loose and had a deep caries.
Excessive lower incisor display was present during smiling
Figure 1. (A) General appearance of patient
presenting a normal mandibula, a
decreased lower facial height and a
retrusive maxilla, (B) Side appearance of
patient, (C) Syndromic facial appearance
of patient, (D) Bowed tibias and general
appearance of lower extremities,
(E) Bowed tibias, (F) Severe digital
abnormalities at feet of patients, and (G)
Roentgen graphics of feet.
G1 G2 G3
Case Report
(Figure 3). Notable radiographic features such as mesioan-
gular mandibular left fi rst premolar and distoangular max-
illary right canine were marked, despite adequacy of each
space. Also maxillary right incisor and canine had dilacer-
ated roots. Germs of the maxillary second right and left
second molars could be visualized in radiographic evalua-
tion. Analysis of the lateral cephalometric radiographs in-
dicated a retrusive maxilla, a normal mandible and a de-
creased lower facial height (Figure 3A,B). Maxillary incisors
were upright and mandibular incisors were retroclined re-
sulting in an excessive interincisal angle. Bilateral palatal
clefts of the patient were operated at earlier age. On the
other hand a fi stula was observed on the right side of the
palate (Figure 2B).
Abdominal and pelvic sonography revealed normal fi nd-
ings. Echocardiography was normal. MRI of brain and pineal
gland were normal. Cervical and thoracal spine MRI fi ndings
were normal except torticollis. Bone survey was performed.
Roentgenograms of chest, upper limbs and pelvis were nor-
mal (Figure 4). Lower thoracal and lumbar vertebral bodies
were slightly rounded anteriorly. On anteroposterior and
lateral head roentgenograms, mandible was slightly angled
to the right because of torticollis and mentum were point-
ed (Figure 4). The teeth were displaced and some of them
were deformed. While femura and patellas were bilaterally
normal; tibias were short and bowed. Fibulas were aplasic
and there was an extra, short, thick bony structure with a
small distal epiphysis adjacent to the femoral condyles on
the right side. Tibiofemoral and tibiotalar joints were dis-
located bilaterally. Feet were slightly small and tarsal bones
were osteopenic. Medial and navicular bones were fused and
medial cuneiforms were long bilaterally. In both feet, fi rst
metatarsal bones were short and phalanges were varying of
length and width (Figure 1G). We received informed con-
sent of the parents about this case description.
Cytogenetic analysis and fi ndings
The patient and her families’ chromosomal analyses were
performed on cultured peripheral blood lymphocytes. Slides
were processed for Trypsin-Giemsa banding. Twenty meta-
phases were microscopically analyzed for each case. A nor-
mal chromosome complement was found for the patient
(46,XX). Karyotypes of her parents and siblings were also
normal (46,XX and 46,XY).
Sometimes it is very diffi cult to discriminate the syndromes.
A diagnosis should be rendered only when there is a close re-
semblance between the case and the syndrome, so individu-
als with multiple defects may have conditions or syndromes
that have not yet been defi ned. From this point of view, here
in we report a new syndrome with bilateral fi bular agenesis,
torticollis, labial hypoplasia, dysmorphic facial features, cleft
palate and absence of multiple permanent teeth.
The prominent feature of our case was very short stature
because of fi bular agenesis and tibial bowing. The arms,
forearms, and digits of arms were normal. In Fuhrmann
syndrome; alhypoplasia of fi bulae, hip dislocation, bowed
femora, clup foot, oligodactyly, alterations of tali and cal-
canei, alhypoplastic toe nails, and hand pathologies are re-
ported [6]. Hypoplasia of fi bulae and ulnar abnormalities
are also reported in other syndromes [2,4,6,8]. Another ma-
jor feature of our case was absence of multiple permanent
teeth with cleft palate, and fl at face. In all syndromes and
new entities defi ned with fi bular agenesis in the literature,
no teeth abnormalities are reported. Cleft palate and teeth
pathologies are different entities, as these organs are devel-
oped from different origins in embryogenesis.
Our patient had digital abnormalities in lower extremities;
however no clinical or radiological pathologies are detect-
ed in upper extremities (limps). All cases reported in the
literature with fi bular agenesis have been inherited as an
autosomal recessive or dominant manner or sporadically
[2,9–11]. Our patient was the fi rst case of the large family
with a congenital malformation and there was not a con-
sanguinity between parents. So this may indicate that the
case may be sporadic. Any infectious disease, teratogenes,
medications, alcohol, smoking, x-ray, and trauma contrib-
uting to these detholojic features have not been reported
in prenatal history. The only cause of premature born was
cervix insuffi ciency.
Clinicians have done the detailed examination of the fea-
tures of mouth and face. Facial features of the children are
Figure 2. (A) Concincident dental midlines, (B) Fistula localized on
the right side of the palate.
Demirhan O et al – Demirhan sydrome, a new sydrome…
frequently referred as dysmorphic when they vary from what
is considered normal. Features such as the spacing between
the eyes, the position and shape of the ears, and the relative
proportions of the maxilla and mandible either are within
the range of normal or vary; enough to be considered dys-
morphic. Additionally, several are limited to oral structures
such as hypodontia, microdontia, micrognathia, and cleft
lip and palate. The case presented in this paper can’t able
to hold her head in straight up while postural rest position.
She has a concave profi le due to retrognatic maxilla. The
retrusive position of the maxilla may be due to the lip clo-
sure in infancy [12]. The basic philosophy of treatment of
such cases are related to correcting the problem surgical-
ly as early as possible so that normal function, growth, and
development could then result. On the other hand, scar-
ring of the tissue that accounts for many of the classic cra-
niofacial effects ascribed to the clefting itself.
Generally, a variety of morphological defects has been re-
ported in the dentition associated with cleft lip, such as hy-
poplasia, germination, accessory cusps, dilacerations, and
microform teeth [13]. Clinical fi ndings of our patient are
exhibiting most of the morphological defects listed above.
She has 5 missing teeth, abnormal shaped maxillary later-
Figure 3. Presentation of excessive lower incisor
display during smiling by view of photo
and roentgenogram. (A,B) Analysis of
the lateral cephlometric radiographs
indicated a retrusive maxilla, abnormal
mandibula and a decreased lower facial
Figure 4. Roentgen graphics of AP head, lateral
chest, lateral neck and AP pelvis.
Case Report
al and mandibular central incisors, and maxillary right in-
cisor and canine with dilacerated roots.
The clinical fi ndings of this case is not in accordance with
any known syndrome. Although the etiology of this dis-
ease is unknown, a strong, complex genetic component
has been implicated. It is a new syndrome according to
our opinion.
All clinical and laboratory studies were performed in Faculty
of Medicine, Çukurova University, Adana-Turkey.
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ResearchGate has not been able to resolve any citations for this publication.
Proximal femoral focal deficiency (PFFD) and fibular a/hypoplasia (FAH) are distinct malformations of the lower limbs. Both can occur as isolated defects or in association with other limb malformations. In fact, fibular defects frequently are present in PFFD, and, conversely, femoral abnormalities can be found in the presence of a typical FAH picture. We report on 5 patients with a variable combination of femoral and fibular defects. In one of them unilateral PFFD was associated with lateral foot defects, in the absence of fibular abnormalities, and with a phenotype similar to that observed in the femoral hypoplasia/unusual face syndrome (FH/UFS). Another patient had isolated PFFD on one side, with controlateral absence of femur, fibula, and tibia. Another patient had a PFFD, fibular hypoplasia, and abnormalities of fibular foot rays, and the last 2 patients, a father and son, had, respectively, bilateral foot malformations plus fibular and tibial hypoplasia in the father and a PFFD in the son. These observations represent a further demonstration of the existence of a fibular developmental field, and contribute to the definition of its spatial boundaries. The variable involvement of elements comprised in the developmental field can be explained by multifactorial etiology. © 1995 Wiley-Liss, Inc.
We describe 2 patients with bilateral right-angle bowing of femora, absence of fibulae, and reduced, flattened and nail-less toes and symmetrical fingernail deficiency in a consanguineous family of ethnic South Vietnamese Baptists and a non-consanguineous Polish family. These cases are similar to those reported by Fuhrmann et al. (in "Skeletal Dysplasias," New York: Alan R. Liss, Inc., pp 519-524), indicating possible autosomal recessive inheritance of this rare non-lethal limb malformation syndrome.
A complex dysostosis characterized by brachy- and/or ectrodactyly and fibular hypoplasia was found in two distantly related individuals. The proposita, aged 25 years, showed metacarpal and phalangeal hypoplasia on both hands, ectrodactyly on both feet, and nearly complete bilateral absence of the fibula. Only milder acromelic defects were detected in a second cousin. A similar pattern of skeletal involvement had been previously described in an unrelated Italian family. The peculiar segregation pattern can be explained by autosomal dominant inheritance with low penetrance and variable expressivity.
Short-limb dwarfism is of heterogeneous origin and has various clinical manifestations. This communication describes a previously apparently unreported type of short-limb dwarfism in 3 affected sibs. Characteristics of this syndrome are bilateral absence of fibulae and severe abnormalities of all digits.
We report on two boys with oto-palato-digital syndrome type II, characterized by growth retardation, bowed long bones, missing or hypoplastic fibulae, sclerosis of the skull base and wavy, irregular clavicles and ribs. The facial appearance is distinctive due to prominent forehead, widely spaced eyes, antimongologid slant of palpebral fissures, flattened nasal bridge and retrogenia. The mother of one patient showed a mild manifestation of oto-palato-digital syndrome type II. Only about 20 cases of this rare X-linked disorder have been reported so far. The similarities and dissimilarities to oto-palato-digital syndrome type I are discussed.
We present a rare case of bilateral absence of fibula, hypoplastic femurs, ankylosis of knee joints and talipes equinovarus in a woman who had a previously affected offspring with similar defects. Antenatal diagnosis, management and a short review of the literature are presented.
Congenital bilateral fibular deficiency with facial dysmorphia, brachydactyly and mental retardation in which are combined in a syndrome or which do not fit in any of the known syndromes. We report a child with congenital bilateral deficiency of the fibula and an unusual combination of features. The patient, a girl, was born after an uneventful pregnancy at term to young healthy parents. Absent fibulae were noted at birth. At age 4 she was found to have growth retardation with delayed bone age, overlapping, short toes, syndactyly of the toes, clinodactyly of the 5th and 2nd fingers, syndactyly of the three last fingers and facial dysmorphia. Mental retardation was present. Karyotype and laboratory investigations were normal. Differential diagnosis included syndromes with aplasia or hypoplasia of fibula, but none of these syndromes seemed to include the girl's features.
Fibular aplasia with split hand/foot or other defects of the central axis is a rare disorder that shares several characteristics with the better known tibial aplasia-ectrodactyly syndrome. They appear to be inherited in an autosomal dominant fashion. In both, however, the phenotype is markedly variable, penetrance is reduced, and apparently sporadic cases are relatively frequent. We report a new case of this disorder and review the clinical and demographic findings in 47 others identified from the literature or other sources. A key observation was that the sex ratio is biased toward males, especially in apparently sporadic cases. This male bias is largely explained by a lower penetrance rate in women. Both affected males and females had affected children, but the risk to offspring was higher when the mother carried the gene, in keeping with a mixed model for genetic susceptibility, i.e., the penetrance of the major predisposing gene is acting against a multifactorially determined level of liability. Given the high degree of nonpenetrance and very variable expressivity, counseling with respect to recurrence risk is problematic and will likely remain so, even when the major predisposing gene is identified.
We describe two unrelated boys with bilateral fibula aplasia, poly- and oligodactyly, and bowed tibiae in two non-consanguineous Brazilian families. These cases are similar to those reported by Fuhrman et al. [(1980). Skeletal Dysplasias. New York: Alan R. Liss Inc. pp. 519-524].
The ulnar-mammary syndrome (MIM 181450) includes postaxial ray defects, abnormalities of growth, delayed sexual development, and mammary and apocrine gland hypoplasia. Brachydactyly type E (MIM 113300) presents with shortening of the metacarpals and phalanges in the ulnar ray in association with moderately short stature. We describe a three-generation family with variable expression of ulnar/fibular hypoplasia, brachydactyly, ulnar ray defects and short stature. The proband had ulnar hypoplasia with missing IV-Vth fingers, fibular hypoplasia on the right, bilateral club feet, growth retardation, a hypoplastic mid-face, an ASD and hemangiomas. She had normal mammary tissue and normal sweating. The mother had short stature, midfacial hypoplasia, a hypoplastic ulna and hypoplasia of the IVth metacarpal (brachydactyly) on the right without other associated malformations. The maternal grandfather had mild bilateral fibular hypoplasia and midphalangeal brachydactyly of the IV-Vth toes. His sister had mild short stature and shortening of the IVth metacarpal of the left hand. Two-point linkage analysis with microsatellite markers spanning the Ulnar-Mammary locus at 12q24.1 did not confirm linkage. The patients may have a previously undescribed syndrome.