CatelManzke Syndrome: A Clinical ReportSuggesting Autosomal Recessive InheritancePelin Ozlem Simsek Kiper,* Gulen Eda Utine, Koray Boduroglu, and Yasemin AlanayPediatric Genetics Unit, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
Received 22 March 2011; Accepted 1 June 2011
We describe a 3-month-old male infant with cleft palate, glos-
soptosis,micrognathia, andbilateral clinodactyly, an association
which is characteristic of CatelManzke syndrome. In addition,the patient had ligamentous laxity in the knee which is a rare
finding of this syndrome. The mode of inheritance of CatelManzke syndrome is unknown. Most cases are thought to be
sporadic but the present patient with consanguinity between
the parents and a possibly affected sib provide support for
autosomal recessive inheritance. 2011 Wiley-Liss, Inc.
Key words: CatelManzke syndrome; cleft palate; autosomalrecessive inheritance; Pierre Robin sequence
CatelManzke syndrome is a rare genetic disorder characterized bythe association of Pierre Robin sequencewith digital abnormalities.
It was first described in 1961 byCatel who reported on a 6-week-old
male infant with cleft palate, glossoptosis, micrognathia, and an
accessory ossification center at the base of the proximal phalanx of
the index finger leading to bilateral clinodactyly. In 1966, Manzke
reported additional details on the same patient, noting that the
supernumerary ossification center was a distinct form of hyper-
phalangism. Further descriptions of cases involving finger anoma-
lies in associationwithPierreRobin sequence led to thedefinitionof
this condition,whichwas given thenameCatelManzke syndrome.The mode of inheritance of this rare syndrome is still unknown.
Themajority of reported patients have beenmale but an increasing
number of female patients are being reported, making an X-linked
inheritance unlikely. The present patient has classical features of the
CatelManzke syndrome. In addition, he has ligamentous laxity inthe knee. The consanguinity between the parents and the presence
of another affected sib in the family suggest autosomal recessive
A 3-month-old male infant was referred to the clinic with atypical
facial features and cleft palate. The patient was born to healthy
consanguineous parents (Fig. 1). Themother was 23 and father was
28 years old. Mothers height and body weight were 163 cm (75th
centile) and 60 kg (75th centile), respectively and her head circum-
ference was 55 cm (mean); fathers height and body weight were
170 cm (25th centile) and 80 kg (9097th centile), respectively. Hishead circumference was 56 cm (mean). Both the mother and the
father did not have any systemic diseases. Their clinical examina-
tions including cardiovascular, respiratory, genitourinary, gastro-
intestinal, and nervous systemswere normal. The first pregnancy of
this couple was a term female who died on the postnatal 13th day.
She had short extremities, cleft palate, and vertebral anomalies. The
second pregnancy was an intrauterine demise lost at term. This
female fetus also had short extremities and kyphoscoliosis. The
third pregnancywas a spontaneous abortion. The fourth pregnancy
was the present patient. Prenatally, nuchal edema and polyhy-
dramnios were noted in the second trimester of the present
patient. Detailed fetal ultrasonography showed bilateral clinodac-
tyly, shortness in the extremities, and scoliosis. Amniocentesis
revealed 46, XY. Medical termination was suggested but the family
The patient was born at term, via normal delivery, with a birth
weight of 3,000 g (25th centile). No resuscitation was required
initially but later on he had cyanosis and difficulty in breathing. He
was then noted to have a cleft palate. After the improvement of
respiratory distress and stabilization of the patient, he was referred
to our hospital for further evaluation. At admission, body weight
was 2,800 g (
pectus carinatum, bilateral clinodactyly, and ligamentous laxity in
the knee were noted (Fig. 2). He had a systolic cardiac murmur.
Cardiac examination by color Doppler echocardiography revealed
a secundum atrial septal defect and patent ductus arteriosus
requiring no medical intervention. Radiographs of both hands
and feet revealed metacarpophalangeal and metatarsaphalangeal
extra ossification centers (Figs. 3 and 4). Radiographs of the lower
extremities and spine were normal (Fig. 5A,B). The patient was
clinically and radiographically diagnosed as CatelManzkesyndrome.
CatelManzke syndrome is rare, and characteristic hallmarksinclude Pierre Robin sequence, bilateral hyperphalangy, and
clinodactyly of the index finger. Typical hand abnormality is
bilateral shortening and radial deviation of the index finger due
to an accessory bone at the metacarpophalangeal joint. The
FIG. 1. The pedigree of the patient.
FIG. 2. Facial phenotype of the patient. Note micro-retrognathia, full
cheeks, low-set ears with helix malformation, narrow thorax,
abdominal distention, digital abnormalities of both hands and feet,
loose skin, and midline cleft of the soft palate. [Color figure can be
seen in the online version of this article, available at http://
FIG. 3. Digital abnormalities of both hands. Note clinodactyly of
index, third and fourth fingers of right hand along with clinodactyly
of index and fourth fingers of left hand. Extrametacarpophalangeal
ossifications can be seen in the radiograph. [Color figure can be
seen in the online version of this article, available at http://
KIPER ET AL. 2289
hyperphalangism in CatelManzke syndrome is a distinct form ofhyperphalangism as Manzke first discussed in 1966. The present
patient withmicrognathia, glossoptosis, cleft palate, and associated
upper respiratory obstruction, together with digital defect readily
fulfills the diagnostic criteria for CatelManzke syndrome.There are over 30 reported cases of CatelManzke syndrome,
some of which do not fulfill the criteria of this specific syndrome
[Manzke et al., 2008]. Pierre Robin sequence, which is an associated
finding in about 80% of cases, is normally a combination of
micrognathia and glossoptosis, with or without cleft palate
[Sheffield et al., 1987]. Not all patients affected with CatelManzkeManzke syndrome show the full range of this sequence [Thompson
and Winter, 1986; Puri and Phadke, 2003; Clarkson et al., 2004;
Manzke et al., 2008]. Therefore, we agree withManzke et al. 
that the term palato-digital syndrome is incorrect and should
be replaced by the term micrognathia-digital syndrome if an
alternative to CatelManzke is to be preferred. The present patienthad cleft palate, micrognathia, and glossoptosis typically showing
the full range of Pierre Robin sequence.
About 70% of the patients with CatelManzke syndrome areknown to have additional congenital abnormalities [Manzke et al.,
2008]. Congenital heart defects are reported in 40% of cases [Puri
and Phadke, 2003]. Our patient had secundum atrial septal defect
and patent ductus arteriosus requiring no medical intervention.
He also had pectus carinatum. Thoracic deformities, such as pectus
carinatum and pectus excavatum, have been reported along with
congenital heart defects in CatelManzke syndrome [Stevensonet al., 1980].Kneedislocationand talipes equinovarus in association
with Pierre Robin sequence were described before [Thompson and
Winter, 1986].Thepresent patient alsohadprominent ligamentous
laxity specifically in the knee.
Skeletal abnormalities such as index delta phalanx, clinodactyly
of the fifth finger, and an extra delta phalanx at the base of the
third phalanx are very common and among the hallmarks of this
syndrome. Metatarsal and toe abnormalities, bifurcation of first
metatarsal, hypoplastic proximal phalanx hallus, or short toes can
also be seen. There is resemblance between the hyperphalangy
phenotype in CatelManzke syndrome and isolated brachydactylytype C which is caused by GDF5 mutations in the majority
of patients. However sequencing of three genes involved in
brachydactyly including GDF5, BMPR1B, NOG revealed no caus-
ative mutations in three CatelManzke patients [Manzke et al.,2008].
Desbuquois dysplasia (DBQD), which is characterized by severe
prenatal andpostnatal growth retardation (
syndrome, which would suggest autosomal or X-linked recessive
inheritance [Gewitz et al., 1978].
The family andpatientwe report onherewith consanguinity and
affected siblings of both genders support previous suggestions of
autosomal recessive mode of inheritance. Until the underlying
molecular mechanism is clear, we suggest caution when counseling
families with a single affected child.
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FIG. 5. A: Radiograph of frontal view of the lower extremities and spine. B: Radiograph of lateral view of the lower extremities and spine.
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