950
Brief clinical and laboratory observations
Cutis gyratum and acanthosis nigricans associated with other anomalies." A distinctive syndrome Roger E. Stevenson, M.D., Gerald J. Ferlauto, M.D., and Harold A. Taylor, Ph.D., Greenwood and Greenville, S. C.
IN 1 9 6 9 , Beare and associates ~ reported a remarkable syndrome characterized by cutis gyratum of the face and limbs, acanthosis nigricans, prominent eyes with hypertelorism, cleft palate, dental anomalies, umbilical protrusion, and bifid scrotum. Herein we present similar findings in a female infant. The features appear sufficiently distinctive to allow differentiation from leprechaunism, Beckwith-Wiedemann syndrome, Crouzon disease, and Seip syndrome. N o cause has been identified. CASE REPORT This is lhe third infant of a healthy 28-year-old black woman. The infant weighed 3,500 gm and was 51 cm long at birth. The pregnancy lasted 40 weeks and was uneventful except for a maternal urinary tract infection treated with ampicillin at four weeks' gestation. One older sister has residual neurologic impairment from prenatal rubella and the other sibling is normal. Apgar scores of 5 and 6 were assigned at i and 5 minutes. Numerous striking abnormalities were immediately obvious. Vertical rugations, measuring 1 to 2 ram, covered the entire forehead and portions of the pinnae, lips, hands, and feet (Figs. 1 and 2). A capillary hemangioma was present in the glabellar area and upper lip. The cranialvault was tall, shortened in its anteroposterior diameter and appeared large in proportion to the face. Head circumference was not measured. The midface was hypoplastic with depression of the nasalbridge and absence ofmalar eminences. The eyes protruded and were wide set. The lids partially covered the eyes, the palpebral fissures slanted downward from the nose, and the eyes deviated externally (Fig. 1). The oral cavity appeared From the Greenwood Genetic Center, and the Department of Pediatrics, Greenville General Hospital. Supported in part by grants from the South Carolina Department of Mental Retardation and the Se~f Foundation. Reprint address: Greenwood;~GeneticCenter, 1020 Spring St., Greenwood, SC 29646.
The Journal of Pediatrics June 1978 small, scarcely accommodating the tongue. The uvula was bifid and the palate short but intact. The pinnae were thick with a fleshy overgrowth of the antitragal area(Fig. I, B). The liver could be palpated several centimeters below the right costal margin and extended across the midline. The umbilical stump was enlarged and skin covered the proximal 3 to 4 cm of the umbilical cord (Fig. 1, A). The female genitalia appeared to be normal except for anterior separation of the labia majora. No masses were present in the labia. The extremities had appropriate length but the soles and palms were deeply furrowed (Fig. 2). The skin of the hands, feet, neck, and axillae were coarse and pigmented, clinically compatible with an acanthosis nigricans. From the time of birth, the infant experienced respiratory difficulty, breathing easier with a mouthpiece in place and requiring oxygen supplementation. Although a tube could be passed through the posterior nares, the nasal pharyngeal airway was narrow, preventing normal nasal respiration. Plastic tubes were placed through the nasal airway at one month of age to facilitate respirations. Because of respiratory difficulty, the infant required gavage feedings. One episode of hypoglycemia occurred in the first day of life but was not associated with seizures or apnea. Laboratory findings included normal intravenous pyelogram, electrocardiogram, computer-assisted tomography of the head, serologic tests for intrauterine infections, chromosome analysis, (standard staining and Q-banding techniques), and serum amino acids. Skull radiographs showed increased vertical diameter of the skull, open cranial sutures, shallow posterior fossa with steep anterior and middle fossas, ocular hypertelorism, and hypoplasia of the facial bones including the mandible. Two episodes of septicemia, one with group D B-hemolytic streptococcus and the other with coagulase positive Staphylococcus aureus complicated the newborn period. The infant grew poorly, gaining less than 250 gm before her death, at age 40 days, caused by respiratory diff• several days after discharge from the intensive care nursery. Autopsy was not permitted by the family. DISCUSSION This infant has numerous features in c o m m o n with the child reported by Beare and associates termed "cutis gyratum, acanthosis nigricans, and other congenital anomalies." In addition to cutis gyratum affecting the forehead, lips, pinnae, hands, and feet, these features include acanthosis nigrieans, tall skull, hypertelorism, proptosis, exotropia, midface hypoplasia, umbilical hernia, and abnormal genitalia. The previously reported infant survived infancy and did n o t have respiratory difficulties during the neonatal period. That patient did have a cleft of the soft palate, natal teeth, partial anodontia, short mandible, functional pyloric stenosis, and delayed developmental milestones. Testing at age two years showed mild impairment o f intellectual function. These patients have features c o m m o n to a n u m b e r of recognizable syndromes, yet appear unique when all
0022-3476/78/0692-0950500.30/0
9 1978 The C. V. Mosby Co.
Volume 92 Number 6
Brief clinical and laboratory observations
95 1
Fig. 1. A, Full frontal view demonstrating abnormal facies, cuffs gyratum of face and extremities, hemangioma of midline of face, and cutaneous outgrowth onto umbilical stump. The craniofacial appearance is characterized by a tall skull, ocular hypertelorism with divergent strabismus, oblique palpebral fissures, shallow orbits, low-set ears, and midface hypoplasia. B. Lateral view of pinna showing cutis gyratum, fleshy overgrowth of antitragal area, and absence of earlobe.
Fig. 2. Appearance of hand, A, and foot, B. These surfaces are deeply furrowed and the epidermis has a grainy texture, features are considered. The craniofacial features alone resemble craniofacial dysostosis (Crouzon disease), a dominantly transmitted genetic disorder.'-' Craniofacial dysostosis lacks cutaneous, genital, and umbilical abnormalities. Proptosis, umbilical defect, and hypoglycemia
are seen in Beckwith-Wiedemann syndrome, a condition of unknown etiology? Beckwith-Wiedemann syndrome also has generalized macrosomia and macroglossia but lacks cranial, cutaneous, and genital abnormalities. Cutaneous hyperpigmentation may be seen in Seip syndrome
952
Brief clinical and laboratory observations
(total lipodystrophy) and cutis gyratum was described in the leprechaun-like condition reported by Patterson and Watkins. 4 Neither of these syndromes has the distinctive craniofacial features, umbilical defect, or genital anomalies noted in the presently described condition. No etiologic factor could be found in either the patient reported by Beare et al or in ours. In both casesl the parents and siblings appeared normal.
REFERENCES 1. Beare JM, Dodge JA, and Nevin NC: Cutis gyratum, acanthosis nigricans and other congenital anomalies: A new syndrome, Br J Dermatol 81:241, 1969.
Changes in glomerular basement membrane antigen(s) with age Sudhir K. Anand, M.B.B.S.,* Benjamin H. Landing, M.D., Eva T. Heuser, M.D., David L. Olson, M.D., Carl M. Grushkin, M.D., and Ellin Lieberman, M.D., Los Angeles, Calif. ANTIBODIES to glomerular basement m e m b r a n e found in patients with the Goodpasture syndrome react in vitro and in vivo with normal h u m a n GBM and immunohistologically are demonstrable as linear deposit of i m m u n o globulin G along the GBM. 1' 2 Marquardt et aP have demonstrated that rabbit a n t i - h u m a n GBM antibodies are directed against at least seven distinct GBM antigens. These observations raised the question, are there differences in G B M antigens of adults and older children compared to those of young children, in whom the Goodpasture syndrome is never seen? This study was From the Departments of Pediatrics and Pathology, University of Southern California School of Medicine and the Department of Pathology and Division of Nephrology, Childrens Hospital of Los Angeles. Presented in part at the 47th Annual Meeting of the Society for Pediatric Research, San Francisco, Calif., April 28, 1977. *Reprint address: Division of Nephrology, Childrens Hospital of Los Angeles, P.O. Box 54700 TerminalAnnex, Los( Angeles, CA 90054.
The Journal of Pediatrics June 1978
2. Dodge HW Jr, Wood MW, and Kennedy RLJ: Craniofacial dysostosis: Crouzon's disease, Pediatrics 23:98, 1959. 3. Beckwith JB: Macroglossia, omphalocele, adrenal cytomegaly, gigantism, and hyperplastic visceromegaly, in Bergsma DS, editor: The first conference on the clinical delineation of birth defects. Part II, Malformation syndromes, Baltimore, 1969, The National Foundation, p 188. 4. Patterson JH, and Watkins WL: Leprechaunism in a male infarit, Pediatrics 60:730, 1962. 5. Seip M: Lipodystrophy and gigantism with associated endocrine manifestations: A new diencephalic syndrome? Acta Paediatr 48:555, 1959.
undertaken to determine if there are age-related differences in the binding of h u m a n anti-GBM antibody(s) to h u m a n GBM. MATERIAL
AND METHODS
Kidneys obtained from 29 autopsied patients (ages from newborn to 30 years) were studied. No patient had evidence of renal or a u t o i m m u n e disease during life or at autopsy. In 27 of the 29 patients autopsy was performed within 24 hours after death, and in the other two between 24 and 48 hours after death. The sera containing anti:GBM antibody(s) were obtained from two patients with Goodpasture syndrome, one a nine-year-old child and the other an adult,* Both sera were positive to a dilution of 1:2,048 by indirect immunofluorescence against GBM in sections of normal kidney of a 16-year-old patient. Abbreviation used GBM: glomerular basement membrane The renal tissue obtained at autopsy was frozen in liquid nitrogen and stored at - 7 0 ~ C. in tight containers from one week to six months. The kidneys were sectioned at 4/x with a cryostat and the sections were treated with test serum containing h u m a n anti-GBM antibody(s) (1:1 dilution for the serum from the first patient and 1:4 dilution for the serum from the second patient) for 30 minutes at 23 ~ C, washed three times for two minutes each in phosphate-buffered saline, and then treated with fluorescein-labeled rabbit a n t i - h u m a n IgG (Hyland Laboratories) in 1:4 dilution for 20 minutes. They were then *Serum from the adult patient was kindly provided by Dr, Richard Glassock, Professor of Medicine, UCLA School of Medicine, Harbor General Hospital, Torrance, Calif.
0022-3476/78/0692-0952500.20/0 9 1978 The C. V. Mosby Co.
Brief clinical and laboratory observations
Cutis gyratum and acanthosis nigricans associated with other anomalies." A distinctive syndrome Roger E. Stevenson, M.D., Gerald J. Ferlauto, M.D., and Harold A. Taylor, Ph.D., Greenwood and Greenville, S. C.
IN 1 9 6 9 , Beare and associates ~ reported a remarkable syndrome characterized by cutis gyratum of the face and limbs, acanthosis nigricans, prominent eyes with hypertelorism, cleft palate, dental anomalies, umbilical protrusion, and bifid scrotum. Herein we present similar findings in a female infant. The features appear sufficiently distinctive to allow differentiation from leprechaunism, Beckwith-Wiedemann syndrome, Crouzon disease, and Seip syndrome. N o cause has been identified. CASE REPORT This is lhe third infant of a healthy 28-year-old black woman. The infant weighed 3,500 gm and was 51 cm long at birth. The pregnancy lasted 40 weeks and was uneventful except for a maternal urinary tract infection treated with ampicillin at four weeks' gestation. One older sister has residual neurologic impairment from prenatal rubella and the other sibling is normal. Apgar scores of 5 and 6 were assigned at i and 5 minutes. Numerous striking abnormalities were immediately obvious. Vertical rugations, measuring 1 to 2 ram, covered the entire forehead and portions of the pinnae, lips, hands, and feet (Figs. 1 and 2). A capillary hemangioma was present in the glabellar area and upper lip. The cranialvault was tall, shortened in its anteroposterior diameter and appeared large in proportion to the face. Head circumference was not measured. The midface was hypoplastic with depression of the nasalbridge and absence ofmalar eminences. The eyes protruded and were wide set. The lids partially covered the eyes, the palpebral fissures slanted downward from the nose, and the eyes deviated externally (Fig. 1). The oral cavity appeared From the Greenwood Genetic Center, and the Department of Pediatrics, Greenville General Hospital. Supported in part by grants from the South Carolina Department of Mental Retardation and the Se~f Foundation. Reprint address: Greenwood;~GeneticCenter, 1020 Spring St., Greenwood, SC 29646.
The Journal of Pediatrics June 1978 small, scarcely accommodating the tongue. The uvula was bifid and the palate short but intact. The pinnae were thick with a fleshy overgrowth of the antitragal area(Fig. I, B). The liver could be palpated several centimeters below the right costal margin and extended across the midline. The umbilical stump was enlarged and skin covered the proximal 3 to 4 cm of the umbilical cord (Fig. 1, A). The female genitalia appeared to be normal except for anterior separation of the labia majora. No masses were present in the labia. The extremities had appropriate length but the soles and palms were deeply furrowed (Fig. 2). The skin of the hands, feet, neck, and axillae were coarse and pigmented, clinically compatible with an acanthosis nigricans. From the time of birth, the infant experienced respiratory difficulty, breathing easier with a mouthpiece in place and requiring oxygen supplementation. Although a tube could be passed through the posterior nares, the nasal pharyngeal airway was narrow, preventing normal nasal respiration. Plastic tubes were placed through the nasal airway at one month of age to facilitate respirations. Because of respiratory difficulty, the infant required gavage feedings. One episode of hypoglycemia occurred in the first day of life but was not associated with seizures or apnea. Laboratory findings included normal intravenous pyelogram, electrocardiogram, computer-assisted tomography of the head, serologic tests for intrauterine infections, chromosome analysis, (standard staining and Q-banding techniques), and serum amino acids. Skull radiographs showed increased vertical diameter of the skull, open cranial sutures, shallow posterior fossa with steep anterior and middle fossas, ocular hypertelorism, and hypoplasia of the facial bones including the mandible. Two episodes of septicemia, one with group D B-hemolytic streptococcus and the other with coagulase positive Staphylococcus aureus complicated the newborn period. The infant grew poorly, gaining less than 250 gm before her death, at age 40 days, caused by respiratory diff• several days after discharge from the intensive care nursery. Autopsy was not permitted by the family. DISCUSSION This infant has numerous features in c o m m o n with the child reported by Beare and associates termed "cutis gyratum, acanthosis nigricans, and other congenital anomalies." In addition to cutis gyratum affecting the forehead, lips, pinnae, hands, and feet, these features include acanthosis nigrieans, tall skull, hypertelorism, proptosis, exotropia, midface hypoplasia, umbilical hernia, and abnormal genitalia. The previously reported infant survived infancy and did n o t have respiratory difficulties during the neonatal period. That patient did have a cleft of the soft palate, natal teeth, partial anodontia, short mandible, functional pyloric stenosis, and delayed developmental milestones. Testing at age two years showed mild impairment o f intellectual function. These patients have features c o m m o n to a n u m b e r of recognizable syndromes, yet appear unique when all
0022-3476/78/0692-0950500.30/0
9 1978 The C. V. Mosby Co.
Volume 92 Number 6
Brief clinical and laboratory observations
95 1
Fig. 1. A, Full frontal view demonstrating abnormal facies, cuffs gyratum of face and extremities, hemangioma of midline of face, and cutaneous outgrowth onto umbilical stump. The craniofacial appearance is characterized by a tall skull, ocular hypertelorism with divergent strabismus, oblique palpebral fissures, shallow orbits, low-set ears, and midface hypoplasia. B. Lateral view of pinna showing cutis gyratum, fleshy overgrowth of antitragal area, and absence of earlobe.
Fig. 2. Appearance of hand, A, and foot, B. These surfaces are deeply furrowed and the epidermis has a grainy texture, features are considered. The craniofacial features alone resemble craniofacial dysostosis (Crouzon disease), a dominantly transmitted genetic disorder.'-' Craniofacial dysostosis lacks cutaneous, genital, and umbilical abnormalities. Proptosis, umbilical defect, and hypoglycemia
are seen in Beckwith-Wiedemann syndrome, a condition of unknown etiology? Beckwith-Wiedemann syndrome also has generalized macrosomia and macroglossia but lacks cranial, cutaneous, and genital abnormalities. Cutaneous hyperpigmentation may be seen in Seip syndrome
952
Brief clinical and laboratory observations
(total lipodystrophy) and cutis gyratum was described in the leprechaun-like condition reported by Patterson and Watkins. 4 Neither of these syndromes has the distinctive craniofacial features, umbilical defect, or genital anomalies noted in the presently described condition. No etiologic factor could be found in either the patient reported by Beare et al or in ours. In both casesl the parents and siblings appeared normal.
REFERENCES 1. Beare JM, Dodge JA, and Nevin NC: Cutis gyratum, acanthosis nigricans and other congenital anomalies: A new syndrome, Br J Dermatol 81:241, 1969.
Changes in glomerular basement membrane antigen(s) with age Sudhir K. Anand, M.B.B.S.,* Benjamin H. Landing, M.D., Eva T. Heuser, M.D., David L. Olson, M.D., Carl M. Grushkin, M.D., and Ellin Lieberman, M.D., Los Angeles, Calif. ANTIBODIES to glomerular basement m e m b r a n e found in patients with the Goodpasture syndrome react in vitro and in vivo with normal h u m a n GBM and immunohistologically are demonstrable as linear deposit of i m m u n o globulin G along the GBM. 1' 2 Marquardt et aP have demonstrated that rabbit a n t i - h u m a n GBM antibodies are directed against at least seven distinct GBM antigens. These observations raised the question, are there differences in G B M antigens of adults and older children compared to those of young children, in whom the Goodpasture syndrome is never seen? This study was From the Departments of Pediatrics and Pathology, University of Southern California School of Medicine and the Department of Pathology and Division of Nephrology, Childrens Hospital of Los Angeles. Presented in part at the 47th Annual Meeting of the Society for Pediatric Research, San Francisco, Calif., April 28, 1977. *Reprint address: Division of Nephrology, Childrens Hospital of Los Angeles, P.O. Box 54700 TerminalAnnex, Los( Angeles, CA 90054.
The Journal of Pediatrics June 1978
2. Dodge HW Jr, Wood MW, and Kennedy RLJ: Craniofacial dysostosis: Crouzon's disease, Pediatrics 23:98, 1959. 3. Beckwith JB: Macroglossia, omphalocele, adrenal cytomegaly, gigantism, and hyperplastic visceromegaly, in Bergsma DS, editor: The first conference on the clinical delineation of birth defects. Part II, Malformation syndromes, Baltimore, 1969, The National Foundation, p 188. 4. Patterson JH, and Watkins WL: Leprechaunism in a male infarit, Pediatrics 60:730, 1962. 5. Seip M: Lipodystrophy and gigantism with associated endocrine manifestations: A new diencephalic syndrome? Acta Paediatr 48:555, 1959.
undertaken to determine if there are age-related differences in the binding of h u m a n anti-GBM antibody(s) to h u m a n GBM. MATERIAL
AND METHODS
Kidneys obtained from 29 autopsied patients (ages from newborn to 30 years) were studied. No patient had evidence of renal or a u t o i m m u n e disease during life or at autopsy. In 27 of the 29 patients autopsy was performed within 24 hours after death, and in the other two between 24 and 48 hours after death. The sera containing anti:GBM antibody(s) were obtained from two patients with Goodpasture syndrome, one a nine-year-old child and the other an adult,* Both sera were positive to a dilution of 1:2,048 by indirect immunofluorescence against GBM in sections of normal kidney of a 16-year-old patient. Abbreviation used GBM: glomerular basement membrane The renal tissue obtained at autopsy was frozen in liquid nitrogen and stored at - 7 0 ~ C. in tight containers from one week to six months. The kidneys were sectioned at 4/x with a cryostat and the sections were treated with test serum containing h u m a n anti-GBM antibody(s) (1:1 dilution for the serum from the first patient and 1:4 dilution for the serum from the second patient) for 30 minutes at 23 ~ C, washed three times for two minutes each in phosphate-buffered saline, and then treated with fluorescein-labeled rabbit a n t i - h u m a n IgG (Hyland Laboratories) in 1:4 dilution for 20 minutes. They were then *Serum from the adult patient was kindly provided by Dr, Richard Glassock, Professor of Medicine, UCLA School of Medicine, Harbor General Hospital, Torrance, Calif.
0022-3476/78/0692-0952500.20/0 9 1978 The C. V. Mosby Co.
