Familial Broad Terminal Phalanges With OneIndividual Showing Additional Anomalies

Lorenzo Pavone,1* Giovanni Sorge,1 Vito Pavone,2 Renata Rizzo,1 Martino Ruggieri,1Agata Polizzi,1 and John M. Opitz3,4

1Clinica Pediatrica Universita di Catania, Catania, Italy2Clinica Ortopedica Universita di Catania, Catania, Italy3Foundation for Developmental and Medical Genetics, Helena, Montana4Montana State University, Bozeman

We describe a family with four relativesshowing broad terminal phalanges (BTP) ofthe fingers and toes. One also had mentalretardation, an unusual facial appearance,cleft palate with bifid uvula, and gingivalhyperplasia. The BTP anomaly in this fam-ily seems to be transmitted as an autosomaldominant trait. Am. J. Med. Genet. 71:271–274, 1997. © 1997 Wiley-Liss, Inc.

KEY WORDS: broad terminal phalanges;clubbing of the fingers;drumstick f inger ; digi tanomalies; hypertrophic os-teoarthropathy

INTRODUCTION

We observed a family in which several relatives pre-sented with an unusual anomaly consisting of broadterminal phalanges (BTP) involving all fingers andtoes, ascertained coincidentally through a boy with an‘‘idiopathic’’ MCA/MR syndrome.

CLINICAL REPORT

In addition to the propositus, BTP of fingers and toeswas present in the paternal grandmother, a paternalaunt, and the father of the patient (Fig. 1). The pater-nal grandmother was said to have BTP of fingers andtoes in the absence of any other anomalies. Her intel-ligence was normal and she had neither a cleft palatenor gingival hyperplasia. She died at age 49 years in adiabetic coma.

The paternal aunt was examined and found to havesevere BTP of fingers and toes. She was the most af-fected relative; terminal phalanges of feet and hands

were markedly wide (Fig. 2). She was 36 years old atthe time of this examination without any other anoma-lies and with normal intelligence.

The father was found to have short hands and feet.The distal phalanges of his fingers and toes were broadand the nails were convex, large, and pitted (Fig. 3).The anomaly was more evident than in his son, thepropositus, but there were no other anomalies and hisintelligence was normal.

G.D. was an 8-year-old boy, the first child of non-consanguineous parents born after a normal pregnancyand delivery. His birth weight was 2,850 g, length 49cm, and head circumference (OFC) 33 cm. At birth, abifid uvula and a cleft of the hard palate were noted.These anomalies were treated surgically when the boywas 20 months old. Psychomotor development was de-layed.

The patient was first referred to us at the age of 7years for delayed speech, mental retardation, and ag-gressive behavior. He weighed 26 kg (75th centile); was120 cm tall (50th centile), and his OFC was 53.5 cm(75th centile). He had dark brown hair and dolicho-cephaly with a sloping forehead. His face (Fig. 4) wasunusual, with a low hairline, protruding columella, flatphiltrum, and large mandible. Gingival hyperplasiawas present (Fig. 5). The upper central incisors wereunerupted, the right upper lateral incisor had a notchin the medial margin, and each lower incisor had anotch in the middle of the superior margin. There wasa surgical scar on the palate. The distal phalanges ofthe fingers and toes were broad, with partial cutaneoussyndactyly of the third, fourth, and fifth fingers. Thenails were convex, large (covering the entire ungualbed), and pitted (Fig. 6). The distal phalanx of themiddle finger measured 0.5 cm in height and 2.5 cm inwidth. Radiographs of hands and toes showed thebroad shape of the distal phalanx of all digits (Figs. 7,8). BTP and pitted nails were more pronounced in thefingers than in the toes. No other anomalies werenoted, and examinations of the patient’s heart, internalorgans, and genitalia were normal. No hirsutism waspresent. The boy had an IQ of 50, severe hyperactivitywith behavior disturbances, and clumsy gait. No sei-zures were reported.

Dr. Opitz is currently at Primary Children’s Medical Center,University of Utah, Salt Lake City, UT.

*Correspondence to: Lorenzo Pavone, M.D., Clinica PediatricaUniversita, Viale Andrea Doria 6, 95125 Catania, Italy.

Received 27 March 1996; Accepted 17 December 1996

American Journal of Medical Genetics 71:271–274 (1997)

© 1997 Wiley-Liss, Inc.

Results of high-resolution lymphocyte chromosomes(up to 800 bands), urinary amino acids, and routinelaboratory tests were normal.

DISCUSSION

Four relatives in the family showed an unusual ab-normal shape of the tips of the fingers and toes, whichappeared to be clinically and roentgenographicallymarkedly wide. All digits were involved. Moreover, thepropositus had other, apparently unrelated anomalies,

namely, unusual face, cleft palate with bifid uvula, andgingival hyperplasia.

The digital anomaly observed in this family is akin tothe abnormality of digits 2–5 seen in Rubinstein-Taybisyndrome (RTS) (MIM 180849) [McKusick, 1994]. Inthis syndrome, the fingers have somewhat broad,short, or tufted terminal phalanges [Berry, 1987; Ru-binstein, 1990], and the anomaly is referred to as‘‘broad terminal phalanges’’ (BTP). This term may bemore appropriate than clubbing to describe the blunt-ing and widening of the terminal phalanges of our pa-tients.

‘‘Clubbing of the fingers’’ is a term used in referenceto the ‘‘loss of the natural angle between the nail andthe nail bed in a properly manicured finger, with boggyfluctuation of the nail bed’’ [Weatherall et al., 1996].Clubbing is common in patients with non-inflamma-tory conditions (e.g., severe chronic heart failure, con-genital cyanotic heart diseases, malignancies) and inpatients with chronic inflammatory diseases (e.g., cys-

Fig. 1. Pedigree of the family. Arrow: propositus; barred symbol: per-sonally examined.

Fig. 2. Drawing of paternal aunt’s hand.

Fig. 3. Father’s hand. Note broad distal phalanges and pitted nails.

Fig. 4. Propositus. Facial aspect.

272 Pavone et al.

tic fibrosis, bronchiectasis, inflammatory bowel dis-ease, chronic liver disease, and parasitic infestations)[Braegger et al., 1990; Weatherall et al., 1996]. How-ever, Richter and Hettmannsperger [1994] suggestedthat clubbing might depend on a genetic predisposi-tion. Familial clubbing of the fingers and toes has beenreported either as an isolated anomaly (MIM 119900)[Curth et al., 1961; Fischer et al., 1964; McKusick,1994] or associated with hypertrophic osteoarthropa-thy (MIM 259100) [Currarino et al., 1961; McKusick,1994]. The latter term refers to a well-known syndromeor sequence manifested principally by clubbing of fin-gers and toes, subperiostial proliferation in long bones,and arthropathy [Currarino et al., 1961], with roent-genographic findings in hands and feet resemblingthose seen in our patients (Figs. 7, 8). According toCurth et al. [1961] ‘‘simple’’ clubbed fingers do not dif-fer clinically or roentgenographically from those in fa-milial hypertrophic osteoarthropathy (MIM 259100)

and therefore, they might represent a form of hyper-trophic osteoarthropathy. She concluded that this con-cept would be substantiated if in a single family somerelatives had clubbed fingers alone and others clubbedfingers and hypertrophic osteoarthropathy, or, if in asingle individual the disorder would progress fromclubbed fingers toward hypertrophic osteoarthropathy[Curth et al., 1961]. However, in the family we inves-tigated, the digits did not show either the dorsal-palmarthickening and nail curvature nor the boggy fluctua-tion of the nail bed typical of clubbed fingers, there wasno clinical evidence of arthropathy, and the long bonesof the relatives with BTP and of the propositus werestudied roentgenologically and found to be normal.

The term ‘‘drumstick’’ seems to us not suitable indescribing the appearance of the fingers and toes in ourpatients, since usually the apex of the drumstick finger

Fig. 5. Propositus. Gingival hyperplasia.

Fig. 6. Propositus. The distal phalanges are broad, and the nails arepitted.

Fig. 7. Hand radiographs of propositus. Note abnormal shape of thedistal phalanges of all digits.

Fig. 8. Radiographs of feet of the propositus. Note abnormal shape ofthe distal phalanges.

Familial Broad Terminal Phalanges 273

is rounded. Moreover, the London Dysmorphology Da-tabase (LDDB) [Winter and Baraitser, 1995] does notdistinguish between ‘‘clubbing’’ and ‘‘drumstick’’; inthis program, 36 conditions are listed under bothterms, but none fits the anomaly seen in our family.

Any clinical relationship between the present familyand RTS seems unlikely, since with the exception of theabnormality of digits 2–5, our subjects did not showany other clinical signs of RTS [Rubinstein, 1990].

Two sisters were reported by Palant et al. [1971]with mental retardation, short stature, unusual facialappearance, cleft palate, camptodactyly of the fourthand fifth fingers, broad distal phalanges of the toes,partial syndactyly of the second and third toes, clino-dactyly of the second toes, and valgus deformity of theright foot. Our propositus resembles the patients ofPalant et al. [1971] on the basis of unusual face, cleftpalate, mental retardation, and broadening of distalphalanges of toes, but, except for the last anomaly, allthe other limb abnormalities were absent.

Khalifa and Graham [1994] described a patient andhis mother with pterygium colli, craniofacial abnor-malities, mental retardation, and broad terminal pha-langes. However, both patients had additional digitalanomalies, namely, proximally displaced thumbs andbroad interphalangeal joints; the craniofacial anoma-lies were different from those seen in our patients.

Familial BTP is a rare anomaly and the cause isuncertain. Is BTP a partial growth disorder localized tothe distal phalanges and involving bone, soft tissue,and nail as well? A pathogenetic hypothesis remains tobe established. In the McKusick catalogue [1994] thereis no entry entitled ‘‘broad terminal phalanges.’’ Exten-sive review of the literature in the Index Medicus andMedline, apart from RTS and from syndromes de-scribed by Palant et al. [1971] and Khalifa and Graham[1994], failed to locate similar conditions. It is of inter-est that a few families with a syndrome similar to the

RTS (MIM 180850) [Cotsirilos et al., 1988; Bonioli andBellini, 1989; McKusick, 1994] have been described,where some relatives had exclusively broad terminalphalanges segregating in an autosomal dominant man-ner with incomplete penetrance [Berry, 1987].

As several generations were involved, autosomaldominant inheritance of a single gene seems the mostlikely causal explanation in the present family.

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