fg syndrome in a brazilian child with additional previously unreported signs
TRANSCRIPT
American Journal of Medical Genetics Supplement 2:247-254 (1986) Developmental Field Concept:457-464
Brief Clinical Report: FG Syndrome in a Brazilian Child With Additional Previously Unreported Signs
A. Richieri-Costa
Departmento de Genetica, lnstituto Basic0 de Biologia Medica e Agricola, Universidade Estadual Paulista, Botucatu, SP, Brazil
We report on a Brazilian child with typical manifestations of the FG syndrome. Pigmentary dysplasia, metacarpal fusion and peculiar anatomopathological find- ings are additional undescribed signs.
Key words: FG syndrome, MCAIMR syndrome, imperforate anus, agenesis of the corpus cal- losum, X-linked transmission, pigmentary dysplasia
INTRODUCTION
The FG syndrome is a rare X-linked MCA/MR syndrome first reported by Opitz and Kaveggia [1974]. Distinctive signs of the FG syndrome include mental retardation, characteristic personality and facial appearance, megalencephaly, agene- sis of the corpus callosum, joint contractures and/or camptodactyly, broad thumbs and/or halluces, and imperforate anudsacral dimples [Opitz and Kaveggia, 1974; Opitz et al, 19821. Here we report some additonal findings in the FG syndrome.
CLINICAL REPORT
VRV, a male, was born in 1981 (Fig. 1). Gestation was normal, but vaginal bleeding was noticed in the 7th month. There was no exposure to toxins, infectious agents or X-rays and no trauma was reported. Delivery was through cesarean section at term. Birth weight was 2450 g; length 45 cm; OFC was not recorded. His parents were not consanguineous. There are two normal healthy sisters. Imperforate anus and hypospadias were noticed at birth; inadequate sucking and vomiting began neonatally.
Received for publication November 4, 1985; revision received February 3, 1986.
Address reprint requests to A. Richieri-Costa, Departamento de Genttica, Instituto BBsico de Biologia Mtdica e Agricola, 18610 Botucatu, SP, Brazil.
0 1986 Alan R. Liss, Inc.
248 Richieri-Costa
Fig. 1. The propositus.
Imperforate anus was repaired at day 1 and bilateral inguinal herniae at age 40 days. Neuropsychological development was delayed. Feeding problems, frequent vomiting, and constipation persist into the present.
Examination at 3 years: weight 11.2 kg (> 3rd centile), height 85 cm (> 3rd centile), OFC 49 cm (50th centile), upper/lower segment ratio 1.36 (normal for age: 1.30), inner canthal distance 2.7 cm (75th centile), outer canthal distance 8.1 cm, philtrum length 1.2 cm, intercommissural distance 3.6 cm, left ear 4.8 cm, right ear 5.1 cm; right palm length 6.3 cm, and right index finger 4.5 cm; internipple distance 12.5 cm (all normal measurements). Thus, he had: mental retardation; short stature; mild hypotonia; brachycephaly; wide forehead; large eyes with apparent large cor- neae; mild antimongoloid slant of the palpebral fissures; apparent hypertelorism; low- set, asymmetric auricles; cupped helix at left; hypoplasic tragus; low nasal bridge; anteverted nostrils (mild); “curved” upper lips; highly arched palate; mild microre- trognathism; short neck; pectus escavatum; apparent mammary hypertelorism, left supernumerary nipple, undescended left testis, dorsal scoliosis; lumbar lordosis; generalized hypopigmented linear areas in the skin; hyperelastic skin; hyperextensible joints; proximally set thumbs, hypoplastic right 5th finger; camptodactyly of the 5th fingers (PIP); marked proximal syndactyly between toes 2-3 and toes 4-5, tibia1 deviation of toes 1-2; hypoplasia of toes 5 ; and calcaneovalgus deformity. Results of blood laboratory tests were normal. G-banded chromosomes of peripheral lympho- cytes were normal.
Roentgenological examination showed: hamate and capitate fusion at right;
458:DFC
FG Syndrome-Additional Signs 249
Fig. 2. Hand radiographs of the propositus.
Fig. 3. Foot radiographs of the propositus.
TABLE I. Dermatoglyphic Findings in Present Patient
Finger pattern Main lines atd Hypothenar Triradius I I1 I11 IV V A B C D T angle patterns C
Left L' L" L" W L" 3 5" - 9 13' 46" L" Absent Right L' L' L" L" L" 3 7 - 11 13" 48" L" Absent
ab, cd, and total ridge count were not performed due to technical reasons.
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252 Richieri-Costa
Fig. 4. CT of the propositus showing agenesis of corpus callosum.
proximal fusion between right metacarpals 4-5; hypoplastic phalanges of right finger 5 (Fig. 2); hypoplastic right metatarsal 5; and bilateral hypoplastic distal phalanx of toe 5 (Fig. 3). Multiple “spinae bifidae” were seen in cervical, thoraxic and lumbar vertebrae. IVP and renal sonography were normal. CT showed agenesis of corpus callosum (Fig. 4a-f). ECG was normal. Skin biopsy (Haematoxylin and Eosin stain): Reduction of the amount of the melanin pigment of the basal layer, but with normal number of melanocytes. Reduction in number (and volume) and size of the collagen
462:DFC
FG Syndrome-Additional Signs 253
fibers. Sections stained with the Masson-Fontana dye confirm the reduction of pigmentation in the basal layer (without melanophagocytosis of the papillar derma) . Sections stained with Verhoeff dye showed a relative increase of the elastic fibers. The anatomopathological conclusions were: hypomelanosis (consistent with achromic nevus) and hyperelastic skin (of an Ehlers-Danlos-like type). Dermatoglyphic find- ings are in Table I.
DISCUSSION
During the last 10 years, the nine reports on FG syndrome brought the overall number of affected patients to 33 [Opitz and Kaveggia, 1974; Keller et al, 1976; Riccardi et al, 1977; Opitz et al, 1982; Burn and Martin, 1983; Bianchi, 1984; Dellapiccola et al, 1984; Neri et al, 1984 and Thompson et al, 19851. The main clinical manifestations reported up to date are listed in Table 11. The FG syndrome has been defined as a true MCA/MR syndrome with X-linked transmission [Opitz et al, 19821, and the practical implications of the diagnostic and genetic counseling aspects were stressed by Neri et a1 119841.
Here we report on additional signs of the FG syndrome represented by metacar- pal 4-5 fusion and pigmentary dysplasia. The anatomopathological findings of the present case relating to the hypopigmented areas and consisting of reduction of melanin pigmentation, reduction of collagen fibers, and relative increase of the elastic fibers most likely represent related findings which would (also) explain some of the clinical signs of the FG syndrome involving the musculoskeletal system, such as: hyperelastic shn, hyperextensible joints, and some aspects of facial appearance. Several pleitropic mutations seem to exert their effect predominantly on the midline [Opitz, 1982a,b]; Midline involvement in the FG syndrome is strongly suggested by agenesis of the corpus callosum, hypertelorism, imperforate anus, spine abnormali- ties, congenital heart defect, hypospadias, and cleft palate.
Considering the early stage of syndromic delineation and the initial tendency of reporting the most severe cases resulting in a biased spectrum of the FG syndrome [Opitz, 1979; Opitz et al, 19821 the reported additional signs of the present patient help to widen the phenotypic spectrum and the clinical knowledge of the FG syndrome.
ACKNOWLEDGMENTS
The author wishes to thank Dr. John M. Opitz for chechng the diagnosis of the present case and for his constant assistance, and Dr. G16ria M.D.D. Colletto who performed the dermatoglyphic studies. Research supported by CNPq (Grant 30. 1260/85).
REFERENCES
Bianchi DW (1984): FG syndrome in a premature male. Am J Med Genet 19:383-386. Burn J, Martn N (1983): Two related male cousins with odd facies, hypotonia, and severe constipation:
Possible examples of the X-linked FG syndrome. J Med Genet 20:97-99. Dellapiccola B, Zelante L, Cristalli P (1984): Diagnostic definition of the FG syndrome. Am J Med
Genet 19:379-381.
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254 Richieri-Costa
Keller MA, Jones KL, Nyhan WL, Francke U, Dixson B (1976): A new syndrome of mental retardation with craniofacial, limb and anal abnormalities. J Pediatr 88:589-591.
Neri, G, Blumberg B, Miles PV, Opitz JM (1984): Sensorineural deafness in the FG syndrome: Report on four new cases. Am J Med Genet 19:369-377.
Opitz JM (1979): Opitz-Kaveggia (FG) syndrome. In Bergsma D (ed): “Birth Defects Compendium, 2nd ed.” New York: Alan R Liss for the National Foundation-March of Dimes, pp 813-814.
Opitz JM (1982a): The developmental analysis of human congenital anomalies. In “Skeletal Dysplasias. ” New York: Alan R Liss, pp 1543.
Opitz JM (1982b): T6pico IV: 0 conceit0 de campo de desenvolvimento. In “T6picos Recentes de Genttica Clinica. ” Sociedade Brasileira de GBneticalRevista Brasileira de Gtnetica, pp 65;81.
Opitz JM, Kaveggia EG (1974): Studies of malformation syndromes of man XXXIII: The FG syndrome. An X-linked recessive syndrome of multiple congenital anomalies and mental retardation. Z Kinderheilk 117: 1-18.
Opitz JM, Kaveggia EG, Adkins WN Jr, Gilbert EF, Viseskul C, Pettersen JC, Blumberg B (1982): Studies of malformation syndromes of humans XXXIIIC: The FG syndrome-Further studies on three affected individuals from the FG family. Am J Med Genet 12:147-154.
Riccaardi VM, Hassler E, Lubinsky MS (1977): The FG syndrome: Further characterization. Report of a third family, and of a sporadic case. Am J Med Genet 1:47-58.
Thompson EM, Baraitser M, Lindenbaum RH, Zaidi ZH, Kroll JS (1985): The FG syndrome: 7 new cases. Clin Genet 27582-594.
Edited by John M. Opitz and James F. Reynolds
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