Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2015; 19: 4549-4552 Concomitance of types D and E brachydactyly: a case report

T. TÜLAY KOCA 1, F. ÇILEDA ğ ÖZDEMIR 2

1Malatya State Hospital, Physical Medicine and Rehabilitation Clinic, Malatya, Turkey 2Inonu University School of Medicine, Department of Physical Medicine and Rehabilitation, Malatya, Turkey

Abstract. – Here, we present of a 35-year old examination, it was determined that the patient, female diagnosed with an overlapping form of who had kyphotic posture and brachydactyly in non-syndromic brachydactyly types D and E the 3 rd and 4 th finger of the right hand, in the 4th with phenotypic and radiological signs. There finger of the left hand and clinodactyly with was observed to be shortening in the right hand th metacarpal of 3 rd and 4 th fingers and left hand brachdactyly in the 4 toe of the left foot (Fig - metacarpal of 4 th finger and left foot metatarsal ures 1 and 2). It was learned that these deformi - of 4 th toe. There was also shortening of the distal ties had been present since birth and a younger phalanx of the thumbs and thoracic kyphosis. sister had similar shortness of the fingers. There The syndromic form of brachydactyly type E is was no known systemic disease. The menstrual firmly associated with pseudo-hypopthyroidism cycle was regular and there was no known his - as resistance to pthyroid hormone is the most prominent feature. As the patient had normal tory of osteoporosis. In the laboratory tests, the stature, normal laboratory parameters and no results of full blood count, sedimentation, psychomotor developmental delay, the case was parathormon (PTH), vitamin D, calcium, alka - classified as isolated E type brachydactyly. line phosphatase (ALP), thyroid function tests (TFT) and urine tests were all within normal Key Words: limits. In the radiological examination, short - Brachydactyly, Skeletal disorders, Pseudo-hypopara - rd thyroidism. ness of the metacarpal was seen in the 3 and 4th fingers of the right hand and in the 4 th finger of the left hand (Figure 3). In addition, there was bluntness and shortness in the distal pha - Introduction lanx of the thumb on both hands. In the lateral thoracolumbar radiograph, wedging in the tho - Brachydactyly (short digits) is a general term racic vertebrae and increased kyphosis were de - describing extremity malformations characteri - termined. sed by bone dysostosis, with the meaning of dis - proportional shortness in the fingers and toes which develops due to smallness or absence of Discussion metacarpals, metatarsals or phalanxes. Just as brachydactyly may be an isolated malformation, Brachydactyly is a general term describing ex - it may also be a part of a complex malformation tremity malformations characterised by bone syndrome 1. Isolated brachydactyly was first clas - dysostosis, with the meaning of disproportional sified in 1951 by J Bell 2 according to phenotypic shortness in the fingers and toes which develops characteristic digit and bone involvement . due to smallness or absence of metacarpals, me - The case examined here in the light of relevant tatarsals or phalanxes 1. Previous studies have literature is of a 35-year old female patient who shown that bone morphogenic (BMP) pathways presented with complaints of back pain with iso - play a key role in the normal development of di - lated brachydactyly which was classified as a gits and their joints and that these pathways are combination of D and E types. associated directly or indirectly with the genes of brachydactyly disease 3. Case Report Just as brachydactyly may be an isolated mal - A 35-year old female patient presented with formation, it may also be a part of a complex complaints of back pain. In the first physical malformation syndrome 1. Brachydactyly was

Corresponding Author: Tuba Tülay Koca, MD; e-mail: [email protected] 4549 T. Tülay Koca, F. Çileda ğ Özdemir

Figure 3. Shortness in the metacarpals of the 3 rd and 4 th fingers of the right hand and 4 th finger of the left hand can be seen in conventional radiography.

lanxes and ulnar deviation in the 2 nd finger, type D: shortness or widening in the distal phalanx of the 1 st digit of the hand or foot, type E: shortness in one or more metacarpal or metatarsal 1. The classification was modified by Temtamy Figure 1. Shortness in the 3 rd and 4 th fingers of the right and McKusick 4 in 1978. Brachydactyly, defined hand, 4 th finger of the left hand and widening in the distal genetically from genetic skeletal impairments, phalanx of both thumbs can be seen. has been included in the dysostosis group. As the case presented here had shortness in first classified in 1951 by Bell 2 according to phe - more than one metacarpal or metatarsal, the pa - notypic characteristics of digit and bone involve - tient was classified as type E. In addition, type ment . D brachydactyly was seen in the bluntness of According to this classification, type A, short - the distal phalanx of the thumb and phenotypic ness in the middle phalanxes of the digits; type kyphotic posture was observed associated with B, absence of or shortness of the mid and distal wedging in the thoracic vertebrae. There are phalanxes of the digits together with deformity in very few cases in literature of types D and E to - the thumbs and big toes; type C, shortness in the gether. mid and proximal phalanxes of the 2 nd and 3 rd Brachydactyly may also be seen together with fingers, hypersegmentation in the proximal pha - other hand malformations such as syndactyly, polydactyly, shortness and symphalangism. Gene defects have been defined in the vast majority of isolated and syndromic forms. The transfer in isolated brachydactyly is autosomal dominant with different expressivity and penetration 1,5 . Currently, there are many forms of brachy - dactyly which have been defined. Subtypes of brachydactyly show high phenotypic variations. Apart from types A3 and D, isolated forms of brachydactyly are rare. Although variations are shown in all individuals, hand involvement is the dominant characteristic. However, apart from hand involvement, short stature, shoulder dyspla - sia, wedging in the vertebrae, radioulnar and hu - Figure 2. Clinodactyly with brachdactyly in the 4th toe of meroulnar joint anomalies, Madelung deformity, the left foot can be seen. epiphyseal changes, toe anomalies and facial

4550 Concomitance of types D and E brachydactyly: a case report anomalies have been reported 6,7 . In the case pre - is suggested. In a genetic study by KD Williams sented here, a wide variability of brachydactyly et al 10 , a strong relationship was determined be - with hand and foot involvement and thoracic ween chromosome 7p21-7p14 and types D and E wedging was found to contribute to the clinical brachydactyly. phenotype. The current case constitutes an example of ty - Type C brachydactyly is characterised by pical extremity involvement for type E isolated shortness in the mid phalanxes of the index, form. In addition, widening in the distal phalanx middle and little fingers. Shortness may be seen of the first finger in both hands demonstrated the in the first metacarpal in most phalanxes of the characteristic of type D brachydactyly. Therefo - index and middle fingers, which is known as hy - re, it was seen to be appropriate to evaluate the perphalangy or hypersegmentation 8,9 . patient as a combination of non-syndromic types Type E brachydactyly is separated into isola - D and E. ted and syndromic forms. The syndromic form The diagnosis of brachydactyly is made clini - type E brachydactyly occurs in 70-78% of pseu - cally, anthropometrically and radiologically. For dohypoparathyroid patients, and with type E bra - isolated forms a prenatal diagnosis is not neces - chydactyly pseudohypoparathyroidism may be sary, whereas there may be a need in syndromic seen to be part of a complex syndrome such as forms. If there is familial genetic mutation, ante - short stature, mental retardation and hypertensi - natal diagnosis can be made in the 11 th week on. Resistance to parathyroid hormones more at from chorionic villus samples and in the 14 th the thyroid and renal tubule level and associated week from amniocentesis. There is no specific with that, the pseudohypoparathyroidism which approach or treatment choice for all forms of bra - develops, is the most evident clinical characteris - chydactyly. If brachydactyly affects the hand tic. While shortness is seen in all the bones of the functions or leads to cosmetic problems, plastic hand in some patients, in the majority, involve - surgery may be required. Physiotherapy and er - ment is more in the metacarpals and distal pha - gotherapy are useful in the improvement of hand lanxes. As there was shortness in more than one functions. Prognosis varies between different metacarpal and metatarsal, the current patient forms with prognosis in syndromic forms asso - was seen to be consistent with the type E classifi - ciated with the related anomalies 1,4,5,9 . cation and the TFT and PTH levels were normal. Moreover, short stature and mental retardation were not considered 9,10 . Hypocalcemia and hy - Conclusions perphosphatemia may develop in these cases. As a result of the laboratory and clinical evaluation Brachydactyly is a bone dysostosis which of the current patient, syndromic form brachy - shows high phenotypic variability with isolated dactyly was not considered. and syndromic forms. Type E brachydactyly in In isolated type E brachydactyly, four heterozy - particular may show syndromic properties cha - gote mutation has been determined in the homebox racterised by pseudohypothyroidism which deve - C13 gene (HOXD 13, 2q31.1). Phenotypically, lops associated with resistance to PTH and thy - syndactyly in the 3 rd and 4 th fingers, synopoly - roid hormones. In addition, it may be seen in dactyly in the 5 th finger and long distal phalanxes combination with type D brachydactyly. may be seen. The reason for HOXD13 mutation in It is hoped that the presentation of this case affected individuals is the many phenotypic variati - with the rarely seen combination of non-syndro - ons. In most patients, there may be accompanying mic form of type D and E brachydactyly, will shortness in the 3 rd metacarpal and less frequently contribute to literature. in the 4 th and 5 th metacarpals. In the foot, shortness th primarily in the 4 metatarsal and sometimes in the –––––––––––––––– –-– –– 1st , 3 rd and 5 th metatarsals and widening in the hal - Conflict of Interest lux may be seen. In the majority of patients, there The Authors declare that there are no conflicts of interest. is normal stature and retarded psychomotor deve - lopment is not seen 8. There are very few cases in literature where References types D and E brachydactyly are seen in the sa - me patient. As there is phenotypic overlap in ty - 1) TEMTAMY SA, A GLAN MS. Brachydactyly. Orphanet J pes D and E brachydactyly, a common etiology Rare Dis. 2008; 3: 15.

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2) BELL J. On brachydactyly and symphalangism. In: 7) RENNEL C, S TENBACH HL . Epipyhseal dysostosis wit - Penrose LS, ed. Treasury of human inheritance. hout dwarfism. Am J Roentgenol Radium Ther vol 5. London. Cambridge University Pres, 1951; Nucl Med. 1970; 108: 481-487. 5: 1-31. 8) SEO SH, P ARK MJ, K IM SH, K IM OH, P ARK S, C HO SI, P ARK 3) GUO Y, L IANG H, D ENG H. Advanges in the molecu - SS, S EONG MW . Identification of a GDF5 mutation in lar genetics of brachydactyly. Yi Chuan 2012; 34: a Korean patient with brachydactyly type C without 1522-1528. foot involvement. Ann Lab Med 2013; 32: 150-152. 4) TEMTAMY SA, M CKUSICK VA . The Genetics of Hand 9) PEREDA A, G ARIN I, G ARCIA -B ARCINA M, G ENER B, B ERIS - Malformations. New York: Alan R Liss Inc., TAIN E, I BAÑEZ AM, P EREZ DE NANCLARES G. Brachy - 1978. dactyly E: isolated or as a feature of a syndrome. 5) NURAL MS, Y ALIN CT, Y ILDIRIM MÖ, D IREN HB . Braki - Orphanet J Rare Dis 2013; 8: 141. daktili Tip C: Olgu Sunumu. [Brachydactyly type 10) WILLIAMS KD, B LANGERO J, S UBEDI J, J HA B, D YER T, C: a case report]. J Firat Med J 2009; 14: 219- VANDEBERG JL, T OWNE B, W ILLIAMS -B LANGERO S. Non - 221. syndromic brachydactly type D and type E map - 6) FITCH N, J EQUIER S, C OSTOM B. Brachydactyly C, ped to 7p15 in healthy children and adults from short stature, and hip dysplasia. Am J Med Genet the Jirel ethnic group in eastern Nepal. Am J 1979; 4: 157-166. Hum Biol 2013; 25: 743-750.

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