Catel–Manzke syndrome: A clinical report suggesting autosomal recessive inheritance

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  • CLINICAL REPORT

    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

    INTRODUCTION

    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

    inheritance.

    CLINICAL REPORT

    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

    declined.

    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.

    DISCUSSION

    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://

    onlinelibrary.wiley.com/journal/10.1002/(ISSN)1552-4833]

    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://

    onlinelibrary.wiley.com/journal/10.1002/(ISSN)1552-4833]

    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. [2008]

    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.

    REFERENCES

    Clarkson JH, Homfray T, Heron CW, Moss AL. 2004. CatelManzkesyndrome: A case report of a female with severely malformed handsand feet. An extension of the phenotype or a new syndrome? ClinDysmorphol 13:237240.

    Desbuquois G, Grenier B, Michel J, Rossignol C. 1966. Nanisme chon-drodystrophique avec ossification anarchique et polymalformations chezdeux soeurs. Arch Fr Pediatr 23:573587.

    FadenM, Al-Zahrani F, Arafah D, Alkuraya FS. 2010. Mutation of CANT1causes desbuquois dysplasia. Am J Med Genet Part A 152A:11571160.

    Faivre L, Cormier-Daire V, Young I, Bracq H, Finidori G, Padovani JP,Odent S, Lachman R, Munnich A, Maroteaux P, Le Merrer M. 2004.Long-term outcome in desbuquois dysplasia: A follow-up in four adultpatients. Am J Med Genet Part A 124A:5459.

    Gewitz M, Dinwiddie R, Yuille T, Hill E, Carter CO. 1978. Cleft palate andaccessory metacarpal of index finger syndrome: Possible familial occur-rence. J Med Genet 15:162163.

    Huber C, Benedicte O, Bertoli M, ChamiM, FradinM, Alanay Y, Al-GazaliLI, Ausems MGEM, Bitoun P, Cavalcanti DP, Krebs A, Merrer ML,Mortier G, Shafeghati Y, Superti-Furga A, Robertson SP, Goff CL, MudaAO, Paterlini-Brechot P, Munnich A, Cormier-Daire V. 2009. Identi-fication of CANT1mutations in desbuquois dysplasia. Am J HumGenet85:706710.

    Manzke H, Lehmann K, Klopocki E, Caliebe A. 2008. CatelManzkesyndrome: Two new patients and a critical review of the literature.Eur J Med Genet 51:452465.

    FIG. 5. A: Radiograph of frontal view of the lower extremities and spine. B: Radiograph of lateral view of the lower extremities and spine.

    KIPER ET AL. 2291

  • Puri RD, Phadke SR. 2003. CatelManzke syndromewithout cleft palate: Acase report. Clin Dysmorphol 12:279281.

    Sheffield LJ, Reiss JA, Strohm K, Gilding M. 1987. A genetic follow-upstudy of 64 patients with the Pierre Robin complex. Am J Med Genet28:2536.

    Stevenson RE, Taylor HA, Burton OM, Hearn HB. 1980. A digito-palatalsyndrome with associated anomalies of the heart, face, and skeleton.J Med Genet 17:238241.

    Thompson EM, Winter RM, Williams MJ. 1986. A male infant with theCatelManzke syndrome anddislocatable knees. JMedGenet 23:271274.

    2292 AMERICAN JOURNAL OF MEDICAL GENETICS PART A

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