OPD Syndrome
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On the phenotypic overlap between "severe" oto-palato digital type II syndrome
and Larsen syndrome. Variable manifestation of a single autosomal dominant gene.

Alembik Y, Stoll C, Messer J.

Service de Genetique Medicale, Hopital de Hautepierre, Strasbourg.

We report two familial cases of oto-palato-digital (OPD) Type II syndrome, a
father and his son. This family shows that OPDII syndrome is inherited as an
autosomal dominant condition. The similarities between the OPDII syndrome and
the Larsen syndrome are discussed.

PMID: 9219012 [PubMed - indexed for MEDLINE]

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International Journal of Paediatric Dentistry
Volume 16 Issue 4, Pages 286 - 291

Distraction in a case of otopalatodigital syndrome type II

P. BATRA, F. S. RYAN, H. WITHEROW & M. L. CALVERT

Introduction. Otopalatodigital syndrome type II is a rare X-linked recessive disorder with generalized
skeletal dysplasia and hearing anomalies. Its features include conductive hearing loss, unusual facies,
cleft palate, micrognathia, and overlapping flexed fingers and toes. It is a more lethal variant of
otopalatodigital syndrome type I. There are many consistently reported craniofacial and dental
findings; however, no case has been published in dental literature.

Case report. We report a case of otopalatodigital syndrome type II with micrognathia, cleft of the soft
palate, and partial anodontia, and discuss the combined orthodontic and surgical management.

Conclusion. We also discuss the differential diagnosis and consider more recent theories on possible
aetiology as well as clinical management strategies for such cases.

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Radiol Med (Torino)  1987 Sep;74(3):176-84

[Oto-palato-digital syndrome. Clinico-radiological study]

[Article in Italian]

Beluffi G, Pazzaglia UE, Fiori P, Pricca P, Poznanski AK.

Sezione di Radiopediatria, IRCCS Policlinico S. Matteo, Pavia.

Oto-palato-digital (OPD) or Tyabi syndrome is a familiar, X-linked bone
dysplasia with intermediate expression, in females or autosomal dominant with
more severe manifestations in males. In the past both the clinical features
(flat face with sunken and broad nasal bridge, antimongoloid slant of palpebral
fissures, palatoschysis, conductive deafness, short and broad thumbs and big
toes, nail dystrophy) and radiological findings (thick and dense base of the
skull, prominence of supraorbital ridges, middle ear bone deformities with dense
ossicles, large and broad vertebral bodies, posterior defects of neural arches
of the vertebrae, carpal and tarsal bone fusions, short and broad nail
phalanges) have been well described and established. The present report
describes 7 patients (4 females and 3 males) all belonging to the same family
(the first described in this country) and all presenting the clinical and
radiological features of OPD syndrome. A cranial and spinal CT was performed on
one patient, with peculiar findings.

PMID: 3659425 [PubMed - indexed for MEDLINE]

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Hum Genet  1991 Dec;88(2):228-30

Oto-palato-digital syndrome type I: further evidence for assignment of the locus
to Xq28.

Biancalana V, Le Marec B, Odent S, van den Hurk JA, Hanauer A.

INSERM Unite 184, Universite Louis Pasteur, Strasbourg, France.

The oto-palato-digital syndrome (OPD) is a rare X-linked disease with diagnostic
skeletal features, conduction deafness, cleft palate and mild mental
retardation. Differences in clinical presentation between families have led
investigators to classify OPD into two subtypes: type I and type II. A linkage
study performed in one family segregating for OPD I has recently suggested
linkage to three marker loci: DXS15, DXS52 at Xq28, and DXS86 at Xq26. We have
investigated an additional OPD I family for linkage by using distal chromosome
Xq DNA probes. The linkage data and the analysis of recombination events that
have occurred in this family excluded, definitively, the Xq26 region for OPD I,
and provide further support for mapping the mutant gene close to the cluster of
tightly linked markers DXS15, DXS52 and DXS305 at Xq28.

PMID: 1757098 [PubMed - indexed for MEDLINE]

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Genet Couns  1993;4(4):289-94

Multiple congenital anomalies associated with an oto-palato-digital syndrome
type II.

Blanchet P, Lefort G, Eglin MC, Rieu D, Sarda P.

Unite fonctionnelle de Foeto-Pathologie et de Genetique Medicale, Hopital
Arnaud-de-Villeneuve, Montpellier.

We report the case of a male fetus with an oto-palato-digital (OPD) type II
syndrome and multiple congenital anomalies (MCA) including omphalocoele,
hypospadias, thoracic dysplasia, skeletal abnormalities, pulmonary hypoplasia
and an absent right adrenal gland. These MCA are sometimes reported in
Melnick-Needles syndrome, which leads us to discuss the possibility that the
spectrum of malformations in these two syndromes might be due to two allelic
forms of the same X-linked gene.

PMID: 8110417 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1985 Feb;20(2):249-54

Oto-palato-digital syndrome, type II--an X-linked skeletal dysplasia.

Brewster TG, Lachman RS, Kushner DC, Holmes LB, Isler RJ, Rimoin DL.

We report on two male infants with a lethal skeletal dysplasia characterized by
cleft palate, midface hypoplasia, downward-slanting palpebral fissures, small
thorax, and bowed limbs with absent fibulae. The clinical and radiographic
changes are similar to those seen in the recently proposed oto-palato-digital
syndrome, type II [Fitch et al, 1983]. The disorder is X-linked with
heterozygous females being more mildly affected.

PMID: 3976718 [PubMed - indexed for MEDLINE]

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Arch Otolaryngol  1967 Apr;85(4):394-9

The oto-palato-digital (OPD) syndrome.

Buran DJ, Duvall AJ 3rd.

PMID: 6021748 [PubMed - indexed for MEDLINE]

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Anaesthesia  1995 Jul;50(7):641-3

Unexpected brainstem compression following routine surgery in a child with
oto-palato-digital syndrome.

Clark JR, Smith LJ, Kendall BE, Tasker RC, Wilkinson KA.

Department of Paediatric Intensive Care, Hospital for Sick Children, London.

Oto-palato-digital syndrome type 1 is a rare condition with several features of
concern to the anaesthetist. We report a patient who developed respiratory
depression 5 h after general anaesthesia. This was subsequently found to be due
to brainstem compression secondary to congenital deformities of the skull base
and cervical vertebrae.

PMID: 7653767 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1999 Jul 2;85(1):79-81

Infant with manifestations of oto-palato-digital syndrome type II and of
Melnick-Needles syndrome.

Corona-Rivera JR, Corona-Rivera E, Corona-Rivera A, Quiles-Corona M, Velez-Gomez
E, Arana-Gutierrez MA.

Publication Types:
Letter

PMID: 10377016 [PubMed - indexed for MEDLINE]

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Am J Dis Child  1967 Feb;113(2):214-21

The oto-palato-digital syndrome. A new symptom-complex consisting of deafness,
dwarfism, cleft palate, characteristic facies, and a generalized bone dysplasia.

Dudding BA, Gorlin RJ, Langer LO.

PMID: 6019437 [PubMed - indexed for MEDLINE]

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Clin Dysmorphol  1994 Apr;3(2):175-9

Prenatal ultrasound findings in a fetus with otopalatodigital syndrome type II.

Eccles DM, Moore IE, Cook S, Griffin DR, Chitty L, Hall CM, Temple IK.

CRC Genetic Epidemiology Research Group, Princess Anne Hospital, Southampton,
UK.

We describe the prenatal diagnosis and post mortem findings, including fetal
radiographs and bone histology, in a fetus with oto-palato-digital syndrome type
II. The differential diagnosis and recurrence risks are discussed.

PMID: 8055140 [PubMed - indexed for MEDLINE]

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Monatsschr Kinderheilkd  1989 Oct;137(10):681-3

Oto-palato-digital syndrome in an Iranian infant.

Farhud DD, Walizadeh GR, Farhud I.

Department of Human Genetics and Anthropology, Amir-Kabir Hospital, Tehran
Medical Science University, Vallie Assr Sq.

A male infant is presented with wide fontanels, micrognathia, mid-face
hypoplasia, hypertelorism, broad nasal root, down-slanting palpebral fissures,
small thorax, funnel chest, short wide toes, camptodactyly and cutaneous
syndactyly of fingers and toes, dysplastic bones with thin wavy ribs and bowed
femore, cryptorchidism, and hypospadias grade I. The mother of this infant
showed some signs of the same condition, including hypertelorism, micrognathia,
small nose with depressed bridge, flat mid-face, impacted teeth and small chest.
This case shows many similarities to oto-palatal-digital syndrome types I and
II.

PMID: 2555708 [PubMed - indexed for MEDLINE]

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J Radiol Electrol Med Nucl  1974 Feb;55(2):137-42

[A case of dwarfism with oto-palato-digital involvement (author's transl)]

[Article in French]

Farriaux JP, Dubois O, Maroteaux P, Fontaine G.

PMID: 4408413 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1983 Aug;15(4):655-64

The oto-palato-digital syndrome, proposed type II.

Fitch N, Jequier S, Gorlin R.

We present a follow-up of the infant with oral, cranial, facial, and limb
abnormalities described by us in 1976. Since then, several other very similar
cases have been reported. We propose that this syndrome be called the
oto-palato-digital syndrome, type II.

PMID: 6614053 [PubMed - indexed for MEDLINE]

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Am J Hum Genet  1972 Jan;24(1):24-36

Oto-palato-digital syndrome: comparison of clinical and radiographic
manifestations in males and females.

Gall JC Jr, Stern AM, Poznanski AK, Garn SM, Weinstein ED, Hayward JR.

PMID: 5012690 [PubMed - indexed for MEDLINE]

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Pediatr Radiol  1992;22(4):267-9

Oto-palato-digital syndrome type II. Report of two related cases.

Gendall PW, Kozlowski K.

Middlemore Hospital, Auckland, New Zealand.

Two cases with major features of bowed long bones, hypertelorism, mandibular
hypoplasia and hand and foot abnormalities with early neonatal death due to
respiratory failure are presented. The radiologic and clinical findings are in
keeping with oto-palato-digital syndrome type II and differ significantly from
other causes of bowed long bones such as campomelic and kyphomelic dysplasias.

PMID: 1523048 [PubMed - indexed for MEDLINE]

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Oral Surg Oral Med Oral Pathol  1973 Feb;35(2):218-24

The oto-palato-digital (OPD) syndrome in females.

Gorlin RJ, Poznanski AK, Hendon I.

PMID: 4513067 [PubMed - indexed for MEDLINE]

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Am J Dis Child  1967 Aug;114(2):215

Oto-palato-digital syndrome.

Gorlin RJ.

Publication Types:
Letter

PMID: 4951552 [PubMed - indexed for MEDLINE]

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Bol Med Hosp Infant Mex  1984 Sep;41(9):489-93

[Oto-palato-digital syndrome and craniopharyngioma. Apropos of a case]

[Article in Spanish]

Guizar-Vazquez JJ, Sanchez-Aguilar G, Hernandez y Alva LE, Salamanca Gomez F.

PMID: 6497971 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1992 Jan 15;42(2):170-2

Tentative assignment of gene for oto-palato-digital syndrome to distal Xq
(Xq26-q28).

Hoar DI, Field LL, Beards F, Hoganson G, Rollnick B, Hoo JJ.

Department of Pediatrics, University of Calgary/Alberta Children's Hospital
Research Center, Canada.

Detailed physical mapping of oto-palato-digital (OPD) syndrome gene on the
X-chromosome was attempted on a family of 3 generations with 2 affected men.
Although the result remains statistically non-significant, it indicates that the
OPD-I gene might be located on the distal Xq.

PMID: 1733165 [PubMed - indexed for MEDLINE]

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Genet Couns  1995;6(3):233-40

Oto-palato-digital syndrome with features of type I and II in brothers.

Horn D, Nitz I, Bollmann R.

Institute of Medical Genetics, School of Medicine (Charite), Humboldt
University, Berlin.

We report on the oto-palato-digital syndrome (OPD) in two sons of a mother
showing minimal signs of the condition. The index patient, a 10-year-old boy,
presents typical symptoms of OPD type I together with bowing of the long bones
and abnormalities of the thorax and spinal column. During the following
pregnancy ultrasonographic studies of the male fetus in the 16th week of
gestation revealed severe micrognathia, short and wide thumbs, and big toes, and
bowed tibiae. After termination of the pregnancy further features were observed
which fulfilled the diagnostic criteria of both OPD I and II. A possible
explanation of these findings is that OPD type I and II and the features in the
described cases are part of a continuous clinical spectrum of the same
underlying mutation, or that several different alleles are involved in the OPD
type I, type II, and mixed phenotypes.

PMID: 8588852 [PubMed - indexed for MEDLINE]

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Brain Dev  1999 Oct;21(7):488-90

Coexistence of oto-palato-digital syndrome type II and Arnold-Chiari I
malformation in an infant.

Hung PC, Wang HS, Lui TN.

Division of Pediatric Neurology, Chang Gung Children's Hospital, College of
Medicine, Chang Gung University, Taoyuan, Taiwan.

A Taiwanese infant with clinically apparent oto-palato-digital syndrome type II
had Arnold-Chiari I malformation. Arnold-Chiari I malformation has not been
reported previously to occur in association with oto-palato-digital type II
syndrome. The pathogenesis of both conditions has remain unclear although the
Arnold-Cliari I malformation is most likely due to a developmental abnormality
of improperly times or incomplete closure of the neural tube. We propose the
physician who care for children with OPD type II must be aware of one more
condition.

PMID: 10522528 [PubMed - indexed for MEDLINE]

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J Nihon Univ Sch Dent  1983 Mar;25(1):11-26

Oto-palato-digital syndrome observed in a girl and her younger brother.

Kamada K, Nagata Y, Yoneyama H, Numata K, Hashimoto K, Okada E, Tateno M, Araki
M.

PMID: 6575134 [PubMed - indexed for MEDLINE]

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Ann Genet  1984;27(2):79-82

[Oto-palato-digital type II syndrome]

[Article in French]

Kaplan J, Maroteaux P.

A new case of the recently described oto-palato-digital type II is reported. The
authors insist on the characteristic anomalies, the facial dysmorphism, the
overlapping and deviation of the digits, the proximal implantation and
hypoplasia of the big toe, and the deafness. Radiologically, the massive
appearance of the bones, their incurvation, their defective modeling are
characteristic of the syndrome. Life expectancy is often reduced. X-linked
inheritance with minor stigmata in the heterozygous females is well established.

PMID: 6331793 [PubMed - indexed for MEDLINE]
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Journal of Human Genetics

Japanese case of oto-palato-digital syndrome type II: an apparent lack of phenotype–genotype correlation.

T. Kondoh1 , N. Okamoto2, N. Norimatsu1, M. Uetani3, G. Nishimura4 and H. Moriuchi1

(1)  Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto,
Nagasaki 852-8501, Japan
(2)  Department of Planning and Research, Osaka Medical Center and Research Institute for Maternal and
Child Health, Osaka, Japan
(3)  Department of Radiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
(4)  Department of Radiology, Tokyo Metropolitan Kiyose Children’s Hospital, Tokyo, Japan

Abstract  We report the case of a 12 year-old boy with oto-palato-digital syndrome type II (OPD II). He had
various anomalies at birth, including bilateral cataracts, bilateral glaucoma, bilateral severe hearing
impairment, congenital heart defect, umbilical herniation, bowed extremities and constrictions of various
joints. These clinical features and whole body X-ray findings were compatible with OPD II. However, his
ocular disorders such as congenital cataract and glaucoma, and congenital heart defect have never been
associated with OPD II as far as we know. His chromosomal analysis revealed normal karyotype, 46,XY.
Analysis of the filamin A gene using a standard PCR-direct sequencing method determined a C586T
(Arg196Trp) missense mutation in exon 3. Interestingly, the same C586T mutation was reported previously in
a patient with OPD I (mild form). Thus, phenotype–genotype correlation of OPD is lacking in those patients.
Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes,
or to identify other factor(s) that influence the clinical features of this syndrome.
Keywords  Oto-palato-digital syndrome type II - OPDII - Filamin A gene -  FLNA  - Genotype–phenotype
correlation
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Magy Traumatol Orthop Helyreallito Seb  1977;20(1):66-73

[Oto-palato-digital (Taybi) syndrome]

[Article in Hungarian]

Kornel P, Laszlo S.

A case of dysmorphogenetic syndrome, described by Taybi, is reported. The
syndrome is characterized by hardness of hearing of conduction type, submucous
cleft palate and anomalies involving the bony frame, especially the digits.

PMID: 16178 [PubMed - indexed for MEDLINE]

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Pediatr Radiol  1977 Sep 1;6(2):97-102

Oto-Palato-Digital syndrome with severe X-ray changes in two half brothers.

Kozlowski K, Turner G, Scougall J, Harrington J.

The first two cases, reported in Australia of Oto-Palato-Digital syndrome, in
two half brothers and described. They show the most severe X-ray changes ever
reported in this syndrome, and were already full-blown in one of the brothers
who was radiographed at the age of 1 day. These two cases also broaden our
clinical and radiographic spectrum of the disease.

PMID: 896356 [PubMed - indexed for MEDLINE]

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Am J Roentgenol Radium Ther Nucl Med  1967 May;100(1):63-70

The roentgenographic features of the oto-palato-digital (OPD) syndrome.

Langer LO Jr.

PMID: 6023901 [PubMed - indexed for MEDLINE]

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Ann Genet  1988;31(3):155-61

[Oto-palato-digital type I syndrome in five generations. Relationship to the
type II form]

[Article in French]

Le Marec B, Odent S, Bracq E, Bulard MB, Bourdiniere J, Babut JM.

CHU Rennes - Hopital Ponchaillou.

Three cases of oto-palato-digital syndrome (OPD) are described. They are from
the same family, in which the syndrome is an X linked recessive disorder,
transmitted through five generations. These cases are classified rather in the
OPD type I. The limit between OPD I and II is discussed. The hypothesis of two
allelic genes is suggested.

PMID: 3265608 [PubMed - indexed for MEDLINE]

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Ryoikibetsu Shokogun Shirizu  2001;(34 Pt 2):446-8

[Oto-palato-digital syndrome, type II]

[Article in Japanese]

Narahara K.

Department of Pediatrics, Okayama Red Cross General Hospital.

Publication Types:
Review
Review, Tutorial

PMID: 11528829 [PubMed - indexed for MEDLINE]

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Ryoikibetsu Shokogun Shirizu  2001;(34 Pt 2):444-5

[Oto-palato-digital syndrome, type I]

[Article in Japanese]

Narahara K.

Department of Pediatrics, Okayama Red Cross General Hospital.

Publication Types:
Review
Review, Tutorial

PMID: 11528828 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1990 Jun;36(2):226-31

Oto-palato-digital syndrome, type II: evidence for defective intramembranous
ossification.

Ogata T, Matsuo N, Nishimura G, Hajikano H.

Department of Pediatrics, Keio University School of Medicine, Japan.

We report on a Japanese boy with oto-palato-digital syndrome type II, an
X-linked lethal congenital skeletal dysplasia. The clinical, radiological and
histological findings indicate that defective intramembranous ossification may
be the principal abnormality responsible for the entity.

PMID: 2114799 [PubMed - indexed for MEDLINE]

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Clin Genet  1986 Oct;30(4):338-44

Oto-Palato-Digital syndrome in four generations of a large family.

Pazzaglia UE, Beluffi G.

A new large family, affected by O-P-D syndrome is reported. Nine members in four
consecutive generations have been studied. Computerized tomography study of
spine and skull showed abnormalities to be confined to mesodermal derivates,
while nervous structures were normal. Transmission pattern may be X-linked with
intermediate expression in the female or autosomal dominant with sex limitation
of expression.

PMID: 3791682 [PubMed - indexed for MEDLINE]

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Rev Stomatol Chir Maxillofac  1983;84(6):322-9

[Otopalatodigital syndrome. Apropos of 3 female cases]

[Article in French]

Plenier V, Delaire J, David A, Cohen JY.

The oto-palato-digital syndrome about which much has been written on the male
subject is analysed for a case of a mother and her two daughters which exhibited
the main characteristics of the affliction with the exceptions of deafness and
cleft-palate. These two manifestations, quoted in the name of the syndrome will
be tackled later like its mode of transmission which still remains obscure.

PMID: 6583818 [PubMed - indexed for MEDLINE]

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J Laryngol Otol  1976 Apr;90(4):407-11

The oto-palato-digital syndrome.

Podoshin L, Heymans HS, Fradis M.

A boy aged ten years with oto-palato-digital syndrome is discussed. Because of
severe conductive hearing loss tympanotomy was performed and abnormal poorly
mobile ossicles were found. Stapedectomy was performed without improvement of
hearing.

PMID: 1270914 [PubMed - indexed for MEDLINE]

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Clin Genet  1994 Mar;45(3):154-61

Oto-palato-digital syndrome type II in two unrelated boys.

Preis S, Kemperdick H, Majewski F.

Department of Pediatrics, Heinrich Heine Universitat, Dusseldorf, Germany.

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.

Publication Types:
Review
Review of Reported Cases

PMID: 8026107 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1997 Aug 22;71(3):341-7

Comment in:
Am J Med Genet. 1999 Jul 2;85(1):88-9.

Are Melnick-Needles syndrome and oto-palato-digital syndrome type II allelic?
Observations in a four-generation kindred.

Robertson S, Gunn T, Allen B, Chapman C, Becroft D.

Starship Children's Hospital, Auckland, New Zealand.

Melnick-Needles syndrome (MNS) is a female-limited skeletal dysplasia inherited
in a X-linked dominant pattern. Males born to women with MNS may exhibit lethal
multiple congenital anomalies, but recurrence of this phenotype within one
family has not been reported. Males with oto-palato-digital syndrome type II
(OPD II) also demonstrate a multiple congenital anomalies phenotype that
includes skeletal dysplasia but the maternal phenotype includes only mild
craniofacial anomalies. These two syndromes have been suggested as being allelic
despite differences in the described maternal phenotypes. We present a
four-generation kindred in which four males had a consistent multiple congenital
anomalies phenotype. The females in this family have skeletal changes
characteristic of MNS but have only mild craniofacial anomalies and also
deafness attributable to ossicular deformity, traits more commonly found in OPD
II. The expression of manifestations of MNS and OPD II in males and females in
this kindred further suggest that these syndromes are allelic.

PMID: 9268106 [PubMed - indexed for MEDLINE]

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Nat Genet. 2003 Apr;33(4):487-91. Epub 2003 Mar 03. Related Articles, Gene, Nucleotide,
Protein, OMIM, Cited in PMC, Books, LinkOut

Localized mutations in the gene encoding the cytoskeletal protein filamin A cause
diverse malformations in humans.

Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, Kenwrick SJ,
Kim CA, Morava E, Newbury-Ecob R, Orstavik KH, Quarrell OW, Schwartz CE, Shears DJ, Suri M,
Kendrick-Jones J, Wilkie AO; OPD-spectrum Disorders Clinical Collaborative Group.

Weatherall Institute of Molecular Medicine, Room 304, The John Radcliffe, Headley Way, Oxford
OX3 9DS, UK. stephen.robertson@stonebow.otago.ac.nz

Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin
A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the
actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second
messengers. We identified localized mutations in FLNA that conserve the reading frame and lead
to a broad range of congenital malformations, affecting craniofacial structures, skeleton, brain,
viscera and urogenital tract, in four X-linked human disorders: otopalatodigital syndrome types 1
(OPD1; OMIM 311300) and 2 (OPD2; OMIM 304120), frontometaphyseal dysplasia (FMD; OMIM
305620) and Melnick-Needles syndrome (MNS; OMIM 309350). Several mutations are recurrent,
and all are clustered into four regions of the gene: the actin-binding domain and rod domain
repeats 3, 10 and 14/15. Our findings contrast with previous observations that loss of function of
FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration
disorder, called periventricular nodular heterotopia (PVNH; refs. 3-6). The patterns of mutation, X-
chromosome inactivation and phenotypic manifestations in the newly described mutations
indicate that they have gain-of-function effects, implicating filamin A in signaling pathways that
mediate organogenesis in multiple systems during embryonic development.

PMID: 12612583 [PubMed - indexed for MEDLINE]

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Practical Genetics
European Journal of Human Genetics (2007) 15, 3–9. doi:10.1038/sj.ejhg.5201654; published online 23 August 2006

Otopalatodigital syndrome spectrum disorders: otopalatodigital
syndrome types 1 and 2, frontometaphyseal dysplasia and
Melnick-Needles syndrome

Stephen P Robertson

The term otopalatodigital syndrome spectrum disorders is an umbrella category that includes four
phenotypically related conditions, otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and
Melnick–Needles syndrome. The phenotype of these conditions in the male ranges from a severe perinatally
lethal multiple malformation syndrome to a mild skeletal dysplasia. Most, but not all, instances of these
conditions are associated by mutations in the X-linked gene encoding the cytoskeletal protein filamin A.
Mutations in this gene are clustered, exhibit a strong genotype–phenotype correlation and are presumed to
exert their effect by a gain-of-function mechanism.

Keywords: otopalatodigital syndrome 1, otopalatodigital syndrome type 2, Melnick–Needles syndrome,
frontometaphyseal dysplasia, filamin A
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Am J Med Genet  2000 Nov 27;95(3):193-200

Oto-palato-digital syndrome, type II: report of three cases with further
delineation of the chondro-osseous morphology.

Savarirayan R, Cormier-Daire V, Unger S, Lachman RS, Roughley PJ, Wagner SF,
Rimoin DL, Wilcox WR.

Medical Genetics Birth Defects Center, Steven Spielberg Pediatrics Research
Center, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, California
90048, USA.

Oto-palato-digital syndrome type II (OPD II) is a lethal X-linked skeletal
dysplasia with pleiotropic manifestations. The basic defect is not known. There
has been only one detailed report of the chondro-osseous abnormalities in this
condition describing abnormal periosteal ossification in a single case [1990: Am
J Med Genet 36:226-231]. We report on three cases of OPD II emphasizing the
chondro-osseous morphology. Although endochondral ossification was normal,
periosteal ossification was defective with islands of cortical bone aplasia and
hyperplasia of the periosteum. The trabecular bone was also extremely poorly
formed and markedly hypercellular. Both membranous ossification and bone
remodeling appear to be defective in OPD II and should account for part of the
observed phenotype. The biglycan gene maps to Xq28 and is involved in bone
formation, but was excluded as a candidate by direct sequencing of cDNA in one
case. Copyright 2000 Wiley-Liss, Inc.

PMID: 11102922 [PubMed - indexed for MEDLINE]

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Indian J Pediatr  1970 Mar;37(266):112-4

Oto-palato-digital syndrome.

Singh SD, Diwedi MS, Irani M.

PMID: 5505607 [PubMed - indexed for MEDLINE]

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An Esp Pediatr  1984 Jun;20(9):905-10

[Oto-palato-digital syndrome. Report of a case in a female]

[Article in Spanish]

Sirvent Gomez J, Rodriguez Valcarcel G, Alfayate Miguelez S, Pombo Felipe F.

PMID: 6486585 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1990 Jun;36(2):183-95

Atelosteogenesis type III: a distinct skeletal dysplasia with features
overlapping atelosteogenesis and oto-palato-digital syndrome type II.

Stern HJ, Graham JM Jr, Lachman RS, Horton W, Bernini PM, Spiegel PK, Bodurtha
J, Ives EJ, Bocian M, Rimoin DL.

Medical Genetics-Birth Defects Center, Ahmanson Pediatrics Center, Cedars-Sinai
Medical Center, UCLA School of Medicine 90048.

We present 5 cases of a short-limb dwarfism syndrome whose manifestations
overlap those of atelosteogenesis and oto-palato-digital syndrome Type II.
Clinical, radiographic, genetic, and histologic data are presented which
demonstrate differences between our patients and previously reported cases of
these other conditions. We conclude that the disorder seen in these children
represents a distinct chondrodysplasia for which we propose the name
atelosteogenesis Type III.

PMID: 2368807 [PubMed - indexed for MEDLINE]

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Genet Couns  1994;5(1):61-6

Oto-palato-digital syndrome type II.

Stoll C, Alembik Y.

Institut de puericulture, Centre hospitalier et Universitaire, Strasbourg,
France.

We report a patient with a sporadic case of oto-palato-digital (OPD) syndrome
type II. Parents and five previous sibs are normal. At 26 years of age the
patient had conductive hearing impairment, cleft palate, a prominent forehead, a
flat facies, and a broad nasal base resulting in the characteristic "pugilistic"
appearance. Extension and supination were limited at the elbows; thumbs and
halluces were broad. Many radiological abnormalities were noted: malformations
of the cervical spine, pelvic abnormalities, bilateral coxa valga, genu valgum,
small fibulae, pes equino varus, and 15 carpal bones. IQ improved dramatically
from 65 to 95.

PMID: 8031537 [PubMed - indexed for MEDLINE]

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Am J Med Genet 1991 Nov 1;41(2):169-72

Oto-palatal-digital syndrome type II with X-linked cerebellar hypoplasia/hydrocephalus.

Stratton RF, Bluestone DL. South Texas Genetics Center, San Antonio 78229.

We describe an infant with clinically apparent oto-palatal-digital syndrome Type II (OPD II), who,
in addition, also has hydrocephalus and cerebellar hypoplasia. This second X-linked disorder
has not been reported previously to occur in association with OPD II. This patient had 2 maternal
uncles who died neonatally with congenital hydrocephalus and digital abnormalities consistent
with OPD II. We suggest that these 2 entities may be located near one another on the X
chromosome, and that both loci are affected in this family. Publication Types: Review Review of
Reported Cases PMID: 1785627 [PubMed - indexed for MEDLINE]

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Am J Med Genet  1998 Oct 12;79(5):401-2

Hypoplasia of the transverse sinus in oto-palato-digital syndrome type I.

Suzumura H, Kano K, Nishimura G.

Publication Types:
Letter

PMID: 9779811 [PubMed - indexed for MEDLINE]

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Z Orthop Ihre Grenzgeb  1977 Feb;115(1):75-82

[The oto-palato-digital syndrome (Taybi) (author's transl)]

[Article in German]

Szabo L, Perjes K, Mangliar K.

Two girls with typical clinical and radiological signs of the oto-palato-digital
(OPD) syndrome are described. The grade of severity attained that usually seen
only in boys. The patients are thought to be homozygotes for an autosomal
recessive gene, not heterozygote carriers.

PMID: 842092 [PubMed - indexed for MEDLINE]

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Am J Dis Child  1970 Apr;119(4):377

Inheritance of the oto-palato-digital syndrome.

Turner G, Gorlin RJ.

PMID: 5434601 [PubMed - indexed for MEDLINE]

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Am J Med Genet 1993 Feb 15;45(4):481-7 Related Articles, Links

Otopalatodigital syndrome type II associated with omphalocele: report of three cases.

Young K, Barth CK, Moore C, Weaver DD.

Department of Medical and Molecular Genetics, University of Indiana School of Medicine,
Indianapolis 46202-5251.

We present 3 patients with otopalatodigital (OPD) syndrome type II and omphalocele; 2 of the
cases are brothers. There are now 6 known cases of OPD type I or II with omphalocele. We
propose that this combination is not coincidental and discuss mechanisms that may result in the
combination of OPD, omphalocele, and other midline defects.

PMID: 8465856 [PubMed - indexed for MEDLINE]

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Otolaryngol Head Neck Surg  2002 Feb;126(2):129-40

The oto-palato-digital syndrome: variable clinical expressions.

Zaytoun GM, Harboyan G, Kabalan W.

Department of Otolaryngology-Head and Neck Surgery, American University of
Beirut School of Medicine and Medical Center, Makassed General Hospital,
Lebanon. gzaytoun@cyberia.net.lb

The oto-palato-digital (OPD) syndrome is a rare but well-defined disorder
characterized by a skeletal dysplasia of the hands and feet, hearing loss, and
anomalies of the palate. Since it was first described by Taybi in 1962, a little
over 30 cases have been reported in the literature. A more lethal variant of the
syndrome was described later by Fitch and was termed OPD type II. Several
studies were conducted to determine the exact mode of inheritance of this
syndrome, whereas others have focused on the characterization of the skeletal
anomalies and their variations. Otologists were interested in determining the
etiology of the associated hearing loss. We report 4 cases of patients with the
spectrum of anomalies that characterize the OPD syndrome. These patients include
3 siblings and 1 unrelated patient who presented to our service complaining of
hearing loss. The skeletal anomalies, special features, and audiologic findings
are described and compared with those in previously reported cases. A discussion
based on a literature review of the mode of inheritance, of variation in the
clinical expression, and of the etiology of hearing loss is also included.
Finally, we review and discuss the subdivision of this syndrome into the 2 types
(I and II).

PMID: 11870342 [PubMed - indexed for MEDLINE]