American Journal of Medical Genetics 49:224-228 (1994)

Newly Recognized Autosomal Recessive Faciothoracoskeletal Syndrome

A. Richieri-Costa, M.L. Guion-Almeida, J.R.P. Lauris, and D.M. Ferreira SeraiCo de Genktica Clinica, Hospital de Pesquisa e Reabilitqiio de LesBes Labw-Palatais, Uniuersidade de SEio Paulo, Bauru (A.R.-C., J.R.P.L., M.L.G.-A.), and Sera40 de Aconselhamento Gene'tico, Instituto de Bwczncias, Universidade Estadual Paulista, Botucatu (D.MP.), SP, Brazil

We report on 2 brothers, born to consangui- neous parents presenting thin/long face, small ears, blepharophimosis, malar hypo- plasia, long neck, pectus excavatum, brachy- camptodactyly, and sacral dimple. We suspect that these patients represent a previously un- described autosomal recessive syndrome. 0 1994 Wiley-Liss, Inc.

KEY WORDS: blepharophimosis, small ears, camptodactyly, pectus exca- vatum, consanguinity, autoso- ma1 recessive inheritance

INTRODUCTION We have observed a "newly" recognized syndrome of

blepharophimosis associated with other facial anoma- lies, together with camptodactyly, and thoracic and spi- nal involvement in 2 brothers born to consanguineous parents.

CLINICAL REPORT Patient 1

EMS (Fig. 1A and B), the propositus, born in 1981, was the first child of a normal 21-year-old GIP1 woman and her normal 21-year-old related husband (F = 11128). Pregnancy was normal. There were no toxic, infectious, traumatic incidents, or X-ray exposure. De- livery was at 40 weeks gestation through cesarean sec- tion. Birth weight (BW) was 3500 g (50th centile), total body length (TBL) was 50 cm (25th centile), and occip- itofrontal circumference (OFC) was not recorded. Neu- ropsychological development was normal. Chronic con- stipation was present in early infancy, and a barium enema at age 2 years showed megacolon, but surgical correction was not necessary. Since age 2 years he devel- oped tonic-clonic seizures responsive to barbiturates.

Clinical examination at age 11 years showed weight 28.8 kg (10 < P < 25th centile), height 137 cm (25th centile), OFC 51.5 cm ( 6 0 t h centile), inner canthal distance (ICD) 3.5 cm (75 < P < 97th centile), outer canthal distance (OCD) 8.2 cm (25th centile), palpebral fissure length (right/left) 2.3 cm ( 4 0 t h centile), total ear length (rightileft) 4.5 cm (<3rd centile). He pres- ented with a thin and long face, temporal narrowing, hypoplastic supraorbital ridges, short and upslanted palpebral fissures, synophrys, small, low-set and poste- riorly angulated ears with hypoplasticiattached lobule, malar hypoplasia, crowded teeth, thin and long neck, pectus excavatum, winged scapulae, brachycamptodac- tyly, abnormal palmar and digital creases (Fig. 2A and B), mild tibia1 deviation of the feet, brachydactyly of toe 4 (Fig. 31, and sacral dimple (Fig. 4).

Roentgenograms showed mild increasing of the su- tural serrations, thoraxic narrowing, hypoplastic and fused 5th lumbar vertebra (Fig. 51, posterior angulation of the sacrum, and bilateral shortening of metatarsals 4-5. Cephalometric findings are shown in Table I.

Results of routine blood tests were normal. Cytogene- tics analysis showed normal chromosomes (G-banded). Dermatoglyphics showed: left hand: Lu(18), L"(3), L"(81, L"(16), L"(19); main line formula: 9.7.5'.3.13'-t,t , L.O.O.M.L.; mainline index: 5; right hand: L"(15), L"(5),

Received for publication April 17,1993; revision received August 23, 1993.

Address reprint requests to A. Richieri-Costa, ServiGo de GenBt- ica Clinica, HPRLLP-USP, P.O. Box 620,17043 Bauru, SP, Brazil.

6 1994 Wiley-Liss, Inc.

Fig. 1. (A, B) Patient 1.

Faciothoracoskeletd Syndrome 225

Fig. 2. (A, B) Hands of patient 1

Fig. 3. Feet of patient 1.

TABLE I. Cephalometric Measurements

Linear and angular EMS DOS measurements cephs cephs

S-N-A 79.8 77.5 S-N-B 82.6" 81.0" A-N-B - 2Ab - 3.5b

80.1 78.9 9.1

S-N-GN N-S, ANS-PNS N-S, Me-Go 45.1" 46.5"

119.Ob 122.9 37.6"

N-S-Ba ANS-PNS, Me-Go Ar-&-Me 142.1" 142.8" S-N 63.4b 64.6' S-Ba 44.2 42.8 N-Me 107.2' 107.1 N-ANS 47 .2b 45.4b

60.5' 61.9 43Ab

ANS-Me ANS-PNS

c

C

a Larger than normal pattern. Lesser than normal pattern. The point PNS was not identified. Normal pattern compared with

data from M.L. Riolo et al., Center for Human Growth and Develop- ment, University of Michigan, Ann Arbor, 1974.

Fig. 4. Sacral dimple of patient 1.

L"(6), L"(12), L"(10); main line formula: 7.5".4.3.13'-t, O.O.O.L.L.; mainline index: 5.

Patient 2 DOS (Fig. 6A and B), the propositus'brother, was born

in 1982. Pregnancy was normal. There were no toxic, infectious, traumatic incidents, or X-ray exposure. De- livery was at 40 weeks of gestation through cesarean section. BW was 3500 g (50th centile), TBL was 50 cm (25th centile), and OFC was not recorded. Neuropsycho-

226 Richieri-Costa et al.

Fig. 6. (A, B) Patient 2.

Fig. 5. Radiograph of the lumbar vertebrae of patient 1.

logical development was normal. A t age 2 years he devel- oped tonic-clonic seizures responsive to barbiturates.

Clinical examination at age 10 years showed weight 24.3 kg (10th centile), height 132 cm (25th centile), OFC 53.5 cm (>50th centile), ICD 3.6 cm (>97th centile), OCD 8.1 cm (25 < P < 50th centile), palpebral fissure length (right/left) 2.3 cm (<50th centile), total ear length (right/left) 4.9 cm (3 < P < 25th centile). He presented with a thin and long face, temporal narrow-

ing, hypoplastic supraorbital ridges, telecanthus, short and upslanted palpebral fissures, small, low-set and pos- teriorly angulated ears with hypoplasWattached lobule, malar hypoplasia, prognathism, crowded teeth, thin and long neck, pectus excavatum, winged scapulae, brachycamptodactyly, abnormal palmar and digital creases (Fig. 7A and b), brachydactyly of toe 4 (Fig. 8), epigastric hernia, and wide sacral dimple (Fig. 9).

Roentgenograms showed increased sutural serra- tions, thoraxic narrowing, hypoplastic and abnormally modeled 5th lumbar vertebra (Fig. 101, posterior an- gulation of the sacrum, camptobrachydactyly of the fingers (Fig. ll), and bilateral shortening of metatar- sals 4-5. Cephalometric findings are shown in Table I.

Results of routine blood tests were normal. Cytogene- tics analysis showed normal chromosomes (G-banded). Dermatoglyphics showed left hand: L"(18), L"(3), L"(8), L"(16), L"(9); main line formula: 7.5".4.3.13 ' -t ,tb, O.O.O.L.L.; mainline index 5; right hand: L"(15), L"(5), L"(6), L"(121, L"(10); main line formula: 73.4.3.13'- t,O.O.O.L.L.; mainline index: 5.

DISCUSSION Here we report on a "newly" recognized MCA syn-

drome in 2 Brazilian brothers, born to consanguineous

Fig. 7. (A, B) Hands of patient 2.

Faciothoracoskeletal Syndrome 227

Fig. 8. Feet of patient 2.

parents. The disorder involves mainly the face (thin and small face), hands (camptodactyly), thorax (pectus exca- vatum), and spine (lumbar and sacral anomalies) (Table 11). The overall pattern of anomalies observed in our patients is clearly distinct from those observed in the F-syndrome [Grosse et al., 19691, in the Guadalajara

Fig. 10. Radiograph of the lumbar vertebrae of patient 2.

camptodactyly syndrome [Cantu et al., 19801, in the autosomal recessive syndrome of growth retardation, mental deficiency, ptosis, pectus excavatum, and camp- todactyly [Khaldi et al., 19881, and in the Tel-Hashomer syndrome [Goodman et al., 1972; Gollop and Colletto, 1984; Pagnan et al., 1988; Toriello et al., 19901. The

Fig. 9. Sacral dimple of patient 2 Fig. 11. Radiograph of the hands of patient 2.

228 Richieri-Costa et al.

TABLE 11. Clinical Manifestations in Our Patients

EMS DOS Thirdlong face + + Temporal narrowing + + Flat orbital ridges -r + Synophrys + Hypertelorism + + Shortiupslanting palpebral fissures + t SmalYlow-set/posteriorly angulated ears + + Hypoplasticiattached lobule + + Malar hypoplasia + t Prognathism - Crowded teeth + + Thirdlong neck + + Pectus excavatum + + Winged scapulae + t Brachycamptodactyly + + Abnormal palmaridigital creases + + Sacral dimple + + Epigastric hernia - Chronic obstipation + Seizures + t

-

+

+ -

pattern of dermatoglyphics, ulnar loops in all digits, also differs from those of the Tel-Hashomer syndrome. The search for similar cases in the main texts in syndromol- ogy [Gorlin et a]., 1990; McKusick, 19901 shows no simi- lar reported condition. Normal chromosomes, parental consanguinity, and normal parents and relatives sug-

gest autosomal recessive inheritance, however, X-linked inheritance cannot be ruled out due to the recurrence of the condition in 2 brothers.

REFERENCES Cant6 JM, Rivera H, Nazara Z, Rojas Q, Hernandez A, Garcia-Cruz D

(1980): Guadalajara camptodactyly syndrome, a distinct probably autosomal recessive disorder. Clin Genet 18:153-159.

Gollop TR, Colletto GMDD (1984): The Tel Hashomer camptodactyly syndrome in a consanguineous Brazilian family. Am J Med Genet 17:399-406.

Goodman RM, Katznelson MBM, Manor E (1972): Camptodactyly: Occurrence in two new genetic syndromes and its relationship to other syndromes. J Med Genet 9203-212.

Gorlin W , Cohen MM, Jr, Levin LS (1990): “Syndromesofthe Head and Neck,” 3rd ed. New York: Oxford University Press.

Grosse FR, Herrmann J, Opitz JM (1969): The F-form of acropectoro- vertebral dysplasia: The F-syndrome. In Bergsma D (ed): “The First Conference on the Clinical Delineation of Birth Defects. Part III. Limb Malformations.” The National Foundation-March of Dimes. BD:OAS V(3):48-63.

Khaldi F, Bennaceur B, Hammou A, Hamza M, Gharbi HA (1988): An autosomal recessive disorder with retardation of growth, mental deficiency, ptosis, pectus excavatum and camptodactyly. Pediatr Radio1 18:432-435.

McKusick VA (1990): “Mendelian Inheritance in Man: Catalogs of Autosomal Dominant, Autosomal Recessive, and X-Linked Phe- notypes,” 9th ed. Baltimore: Johns Hopkins University Press.

Pagnan NAB, Gollop TR, Lederman H (1988): The Tel Hashomer cam- ptodactyly syndrome: Report of a new case and review of the litera- ture. Am J Med Genet 29:411-417.

’Ibriello HV, Higgins JV, Malvitz T, Waterman DF (1990): Two siblings with Tel Hashomer camptodactyly and mitral valve prolapse. Am J Med Genet 36:398-403.