American Journal of Medical Genetics 44:136-137 (1992)
Brief Clinical Report Further Delineation of the Simpson-Golabi-Behmel (SGB) Syndrome Fiorella Gurrieri, Marco Cappa, and Giovanni Neri Istituto di Genetica Medica, Facolta di Medicina e Chirurgia “A. Gemelli,” U.C.S.C. (F.G., G.N.) and Divisione di Endocrinologia, Ospedale Bambino Gesii, Istituto di Ricerca Scientifica (M.C.), Roma, Italy
The Simpson-Golabi-Behmelsyndrome is an X-linked condition characterized by pre- and postnatal overgrowth, “coarse” face, postaxial polydactyly, midline defects, and psychomotor development ranging from normal to mildly retarded. We report on an additional sporadic patient with novel manifestations, contributing to a more thorough delineation of this syndrome. o 1992 wiley-~iss,Inc. KEY WORDS: X-linked syndrome, overgrowth, coarse face, dilated cardiomyopathy, diaphragmatic hernia, developmental delay INTRODUCTION The Simpson-Golabi-Behmel (SGB) syndrome is an X-linked condition characterized by generally mild intellectual impairment, overgrowth, and multiple congenital anomalies [Neri et al., 19881. Considering that the syndrome is now more widely recognized and new cases are reported, it is important to fully delineate the spectrum of its phenotypic variability. With this purpose, we report on a new sporadic patient who, in addition to the most typical manifestations of the syndrome, also has previously unreported dilated cardiomyopathy and diaphragmatic hernia. CLINICAL REPORT The propositus is the first child of healthy, nonconsanguineous parents. He has a younger brother who is normal. Father was 38 and mother 30 years old at the time of his birth. The pregnancy was complicated by vaginal bleeding in the first trimester. Delivery was
Received for publication April 8,1991;revision received September 26. 1991. Address reprint requests to Giovanni Neri, M.D., Istituto di Genetica Medica, Universita Cattolica, Largo F. Vito 1, 00168 Rorna, Italy.
0 1992 Wiley-Liss, Inc.
difficult and neonatal weight was 4,650 g. Ventricular septa1 defect was diagnosed at birth by ultrasonography. Shortly after birth he was operated on for a diaphragmatic hernia and again at one and 5 years for bilateral inguinal herniae and right cryptorchidism, respectively. He started to walk at 3 years. Chromosomes were normal. At 16 years he had a stocky appearance with height of 193cm, weight of 138kg, and head circumference of 59.7 cm, all values above the 97th centile. The face was long and hypotonic with bitemporal constriction and short, down-slanting palpebral fissures, high nasal bridge, and large mandible (Fig. 1).The mouth was constantly open, with inverted V shape of the upper lip and midline groove under the lower lip; enlarged, furrowed, constantly fasciculating tongue, diastasis of the lower central incisors, and wide open bite. Ears were small, with hypoplastic lobe and prominent antihelix. He had drooping shoulders with pectus excavatum and extra nipples bilaterally, 2 on the right and 3 on the left side, respectively (Fig. 2). The hands were large with broad distal phalanges and dermatoglyphics were: t”,abcd, 2nd, 3rd, and 4th IDDL, L”L”L” W L” on right and t, abcd, 2nd, 3rd, and 4th IDDL, WWWWL“ on left. Feet were flat with short hallux valgus. Genitalia were normal, without macroorchidism. There was marked, generalized hypotonia; deep tendon reflexes were reduced. Heart examination showed tachycardia with 110 beats per minute and a 516 systolic murmur, associated with a 216 diastolic murmur. Routine electrocardiogram (ECG) indicated a left bundle branch block and longterm ECG showed the presence of ventricular extrasystoles. Heart ultrasound showed a widely dilated left ventricle. On cardiac catheterization, performed when the patient was 11years old, subaortic ventricular septal defect with ectasis of the sinus of Valsalva and mild left-right shunt were found. When we examined the patient, we judged him of normal intelligence, in fact bright, painfully aware of his condition, and clearly frustrated with his speech problems, likely due to macroglossia and dental malocclusion. He is a heavy smoker.
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Fig. l a b “Coarse” facial appearance of the patient.
DISCUSSION The SGB syndrome is an X-linked disorder characterized by pre- and postnatal overgrowth, low to normal intelligence, congenital hypotonia, multiple midline malformations, and minor anomalies. Eight families with this condition have been reported to date [Behmel et al., 1984,1988;Golabi and Rosen, 1984; Kaariainen, personal communication, 1981; Neri et al., 1988; Opitz, 1984; Simpson et al., 1973; Konig et al., 19911and only one sporadic patient [Tsukahara et al., 19841. The present patient is the second sporadic case reported. He has classical SGB manifestations with diaphragmatic hernia,, extra nipples, and heart defect. Heart defects have
already been reported in the SGB syndrome, particularly conduction defects, such as A-V block and bundle branch block. Ventricular septa1 defect (VSD) and patent ductus arteriosus (PDA) have also been described. Our patient has full cardiac involvement, ranging from functional (conduction defects with extrasystoles) to anatomical alterations (VSD).In addition he has advanced dilated cardiomyopathy, which could be either idiopathic or secondary t o the underlying heart condition, plus increased pulmonary resistance due to heavy smoking. There is no family history of heart disease, and in particular of dilated cardiomyopathy. This is the first time that dilated cardiomyopathy and diaphragmatic hernia are reported in the SGB syndrome.
REFERENCES Behmel A, Plochl E, Rosenkranz W (1984): A new X-linked dysplasia gigantism syndrome: Identical with Simpson dysplasia syndrome? Hum Genet 67:409-413. Behmel A, Plochl E, Rosenkranz W (1988): A new X-linked dysplasia gigantismi syndrome: Follow up in the first family and a second Austrian family. Am J Med Genet 30:275-285. Golabi M, Rosen L (1984): A new X-linked mental retardation-overgrowth syndrome. Am J Med Genet 17:345-358. KGnig R, Sigrun F, Christoph K, Langenbeck U (1991): SimpsonGolabi-Behmel syndrome with severe cardiac arrhythmias. Am J Med Genet 38:244-247. Neri C, Marini R, Cappa M, Borrelli P, Opitz J M (1988): SimpsonGolabi Behmel syndrome: An X-linked encephalotrophoschisissyndrome. Am J Med Genet 30:287-299. Opitz JM (1984):The Golabi-Rosen syndrome. Report of a second family. Am J Med Genet 17:359-366. Simpson JL, Landey S, New M, German J (1973):A previously unrecognized X-linked syndrome of dysmorphia. BD:OAS XI (2):18-24. Tsukahara M, Tanaka S, Kajii T (1984): A Weaver-like syndrome in a Japanese boy. Clin Genet 25:73-78. Fig. 2. Extra nipples on both sides.
Brief Clinical Report Further Delineation of the Simpson-Golabi-Behmel (SGB) Syndrome Fiorella Gurrieri, Marco Cappa, and Giovanni Neri Istituto di Genetica Medica, Facolta di Medicina e Chirurgia “A. Gemelli,” U.C.S.C. (F.G., G.N.) and Divisione di Endocrinologia, Ospedale Bambino Gesii, Istituto di Ricerca Scientifica (M.C.), Roma, Italy
The Simpson-Golabi-Behmelsyndrome is an X-linked condition characterized by pre- and postnatal overgrowth, “coarse” face, postaxial polydactyly, midline defects, and psychomotor development ranging from normal to mildly retarded. We report on an additional sporadic patient with novel manifestations, contributing to a more thorough delineation of this syndrome. o 1992 wiley-~iss,Inc. KEY WORDS: X-linked syndrome, overgrowth, coarse face, dilated cardiomyopathy, diaphragmatic hernia, developmental delay INTRODUCTION The Simpson-Golabi-Behmel (SGB) syndrome is an X-linked condition characterized by generally mild intellectual impairment, overgrowth, and multiple congenital anomalies [Neri et al., 19881. Considering that the syndrome is now more widely recognized and new cases are reported, it is important to fully delineate the spectrum of its phenotypic variability. With this purpose, we report on a new sporadic patient who, in addition to the most typical manifestations of the syndrome, also has previously unreported dilated cardiomyopathy and diaphragmatic hernia. CLINICAL REPORT The propositus is the first child of healthy, nonconsanguineous parents. He has a younger brother who is normal. Father was 38 and mother 30 years old at the time of his birth. The pregnancy was complicated by vaginal bleeding in the first trimester. Delivery was
Received for publication April 8,1991;revision received September 26. 1991. Address reprint requests to Giovanni Neri, M.D., Istituto di Genetica Medica, Universita Cattolica, Largo F. Vito 1, 00168 Rorna, Italy.
0 1992 Wiley-Liss, Inc.
difficult and neonatal weight was 4,650 g. Ventricular septa1 defect was diagnosed at birth by ultrasonography. Shortly after birth he was operated on for a diaphragmatic hernia and again at one and 5 years for bilateral inguinal herniae and right cryptorchidism, respectively. He started to walk at 3 years. Chromosomes were normal. At 16 years he had a stocky appearance with height of 193cm, weight of 138kg, and head circumference of 59.7 cm, all values above the 97th centile. The face was long and hypotonic with bitemporal constriction and short, down-slanting palpebral fissures, high nasal bridge, and large mandible (Fig. 1).The mouth was constantly open, with inverted V shape of the upper lip and midline groove under the lower lip; enlarged, furrowed, constantly fasciculating tongue, diastasis of the lower central incisors, and wide open bite. Ears were small, with hypoplastic lobe and prominent antihelix. He had drooping shoulders with pectus excavatum and extra nipples bilaterally, 2 on the right and 3 on the left side, respectively (Fig. 2). The hands were large with broad distal phalanges and dermatoglyphics were: t”,abcd, 2nd, 3rd, and 4th IDDL, L”L”L” W L” on right and t, abcd, 2nd, 3rd, and 4th IDDL, WWWWL“ on left. Feet were flat with short hallux valgus. Genitalia were normal, without macroorchidism. There was marked, generalized hypotonia; deep tendon reflexes were reduced. Heart examination showed tachycardia with 110 beats per minute and a 516 systolic murmur, associated with a 216 diastolic murmur. Routine electrocardiogram (ECG) indicated a left bundle branch block and longterm ECG showed the presence of ventricular extrasystoles. Heart ultrasound showed a widely dilated left ventricle. On cardiac catheterization, performed when the patient was 11years old, subaortic ventricular septal defect with ectasis of the sinus of Valsalva and mild left-right shunt were found. When we examined the patient, we judged him of normal intelligence, in fact bright, painfully aware of his condition, and clearly frustrated with his speech problems, likely due to macroglossia and dental malocclusion. He is a heavy smoker.
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137
Fig. l a b “Coarse” facial appearance of the patient.
DISCUSSION The SGB syndrome is an X-linked disorder characterized by pre- and postnatal overgrowth, low to normal intelligence, congenital hypotonia, multiple midline malformations, and minor anomalies. Eight families with this condition have been reported to date [Behmel et al., 1984,1988;Golabi and Rosen, 1984; Kaariainen, personal communication, 1981; Neri et al., 1988; Opitz, 1984; Simpson et al., 1973; Konig et al., 19911and only one sporadic patient [Tsukahara et al., 19841. The present patient is the second sporadic case reported. He has classical SGB manifestations with diaphragmatic hernia,, extra nipples, and heart defect. Heart defects have
already been reported in the SGB syndrome, particularly conduction defects, such as A-V block and bundle branch block. Ventricular septa1 defect (VSD) and patent ductus arteriosus (PDA) have also been described. Our patient has full cardiac involvement, ranging from functional (conduction defects with extrasystoles) to anatomical alterations (VSD).In addition he has advanced dilated cardiomyopathy, which could be either idiopathic or secondary t o the underlying heart condition, plus increased pulmonary resistance due to heavy smoking. There is no family history of heart disease, and in particular of dilated cardiomyopathy. This is the first time that dilated cardiomyopathy and diaphragmatic hernia are reported in the SGB syndrome.
REFERENCES Behmel A, Plochl E, Rosenkranz W (1984): A new X-linked dysplasia gigantism syndrome: Identical with Simpson dysplasia syndrome? Hum Genet 67:409-413. Behmel A, Plochl E, Rosenkranz W (1988): A new X-linked dysplasia gigantismi syndrome: Follow up in the first family and a second Austrian family. Am J Med Genet 30:275-285. Golabi M, Rosen L (1984): A new X-linked mental retardation-overgrowth syndrome. Am J Med Genet 17:345-358. KGnig R, Sigrun F, Christoph K, Langenbeck U (1991): SimpsonGolabi-Behmel syndrome with severe cardiac arrhythmias. Am J Med Genet 38:244-247. Neri C, Marini R, Cappa M, Borrelli P, Opitz J M (1988): SimpsonGolabi Behmel syndrome: An X-linked encephalotrophoschisissyndrome. Am J Med Genet 30:287-299. Opitz JM (1984):The Golabi-Rosen syndrome. Report of a second family. Am J Med Genet 17:359-366. Simpson JL, Landey S, New M, German J (1973):A previously unrecognized X-linked syndrome of dysmorphia. BD:OAS XI (2):18-24. Tsukahara M, Tanaka S, Kajii T (1984): A Weaver-like syndrome in a Japanese boy. Clin Genet 25:73-78. Fig. 2. Extra nipples on both sides.
