Case Report
Clinical Genetics 1990: 37: 481-484
Robinow syndrome: report of two patients with cystic kidney disease LYNNWIENS,D. K. STRICKLAND, BARBARA SNIFFENAND BRADLEYA. WARADY The Children’s Mercy Hospital, Kansas City, Missouri, USA Two patients with Robinow syndrome and cystic kidney disease are described. We propose that this anomaly should be added to the spectrum of malformations associated with the syndrome. Received 20 June, revised 7 December, accepted f o r publirarion 9 December 1989 Key words: cyst; dysplasia; kidney; Robinow syndrome.
Robinow syndrome (fetal face syndrome) is a rare entity first described in 1969. It is characterized by a spectrum of anomalies including mesomelic brachymelia, hemivertebrae, frontal bossing, hypertelorism, brachydactyly, cleft lip/palate, scoliosis, depressed nasal bridge, short stature and genital hypoplasia (Robinow et al. 1969, Portnoy 1979, Lee et al. 1982, Shprintzen et al. 1982). Cystic kidney disease is a previously undescribed finding in such patients. We have cared for two unrelated children with Robinow syndrome and cystic kidney disease. Patient 1 SR., a S-month-old white male infant, was admitted to The Children’s Mercy Hospital for evaluation of cystic kidney disease, tachypnea and generalized duskiness. This patient’s prenatal course was complicated by maternal hypertension and intrauterine growth retardation. A prenatal ultrasound revealed a possible cystic left kidney. The family history was negative for renal disease. An amniocentesis was per-
formed at 20 weeks of gestation and revealed a 46,XY karyotype. No fetal growth was reported during weeks 31 and 32 of pregnancy. Prompted by maternal hypertension an elective cesarean section was performed at 33 weeks of gestation. Findings on initial physical examination included hypertelorisrn, long philtrum, low set ears, bilateral cryptorchidism, micropenis, short forearms and brachydactyly, all felt to be compatible with the diagnosis of Robinow syndrome. There were no vertebral anomalies. Additional findings included a well-delineated left lower quadrant abdominal mass and an anteriorly displaced anus. Radiologic evaluation included an abdominal plain film which revealed a markedly distended cecum and the absence of air in the rectum. A barium enema established the diagnosis of malrotation with anal stenosis. A renal ultrasound was performed at 2 weeks of age and revealed a normal right kidney and a small left kidney with multiple nontommunicating cysts and increased echogznicity in the non-cystic areas. The serum creatinine was 0.3 mg/dl at the time of discharge from the newborn nursery.
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Upon hospital admission at age 5 months, the most prominent findings on physical examination included the patient’s short stature (height and weight less than the 5th percentile) as well as the craniofacial and extremity abnormalities characteristic of Robinow syndrome. In addition, the patient demonstrated a generalized dusky appearance, a Grade I/VI systolic murmur heard best at the left midsternal border, and hepatomegaly with the liver edge palpable 5 cm below the right costal margin. Laboratory data demonstrated the following: BUN 20 mg/dl, creatinine 0.9 mg/dl, urinalysis: specific gravity 1.010, 1+ protein, 0-2 WBC/HPF. A renal ultrasound was performed and confirmed the previous ultrasound findings (Fig. 1). Nuclear renal scintography with technetium-99m diethylenetriamine penta-acidic acid (Tc-99m-DTPA) demonstrated the absence of uptake OF the
left side and normal uptake on the right. Cardiac catheterization was performed and revealed pulmonary hypertension. This was felt to be secondary to idiopathic alveolar hypoventilation and was managed with oxygen, furosemide and digoxin. Patient 2
LV, a 4-year-old Hispanic female, was admitted to The University of Kansas Medical Center for evaluation of a 3-4 cm left upper quadrant abdominal mass noted on routine physical examination. The diagnosis of Robinow syndrome had been made at 6 months of age. The patient had congenital hip dislocation which was treated by abduction splints. A patent ductus arteriosus was treated by surgical lig ation at age 2 years. There was no previous history of hypertension or urinary tract in-
483
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fections, nor was there a family history of kidney disease. Physical examination revealed a thin, petite individual with features characteristic of Robinow syndrome. These included short stature (height and weight less than the 5th percentile), mesomelic brachymelia, hypertelorism, wide palpebral fissures, short upturned nose, triangular shaped mouth and micrognathia. There were no vertebral anomalies. In addition, both kidneys were enlarged and easily palpable. Laboratory data revealed the following values: BUN 21 mg/dl, creatinine - 0.3 mg/dl and creatinine clearance - 106 ml/min/1.73 m2. A renal ultrasound study identified mild to moderately enlarged kidneys with increased echogenicity throughout the cortex and medulla. Multiple macroscopic cysts were present in both kidneys, being most prominent in the upper pole of the right
kidney in the cortical region (Fig. 2). An intravenous pyelogram demonstrated bilaterally enlarged kidneys. A renal scan with Tc 99m DTPA demonstrated prompt and symmetrical blood flow to both kidneys. Split renal functions were 58% on the right and 42% on the left. An abdominal ultrasound did not identify hepatic cysts. Renal ultrasounds of both parents revealed kidneys of normal size, shape and configuration without evidence of cysts. Discussion
The characteristic features of Robinow syndrome include facial anomalies (hypertelorism, anteverted nares, broad nasal bridge, macrocephaly, frontal bossing, long philtrum, cleft lip/palate), musculoskeletal anomalies (short stature, vertebral anomalies, scoliosis, inguinal and umbilical her-
Fig. 2. Renal ultrasound demonstrating moderately enlarged kidney with increased echogenicity in cortex and medulla and multiple cysts.
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nias), hypoplastic genitalia, and cryptorchidism (Robinow et al. 1969, Portnoy 1979, Lee et al. 1982, Shprintzen et al. 1982). The syndrome may be genetically heterogeneous with at least three recognized types (Robinow et al. 1969, Bain et al. 1986). We present two patients with Robinow syndrome and cystic kidney disease, an association which has not previously been reported. It is well recognized that the renal lesions associated with most multiple malformation syndromes are cystic in nature (Ault et al. 1988, Bernstein et al. 1974). The lesions are often poorly described and with an undefined natural history. They may range from severe cystic dysplasia, as seen in Patient no. 1, to asymptomatic microcysts and macrocysts localized to the peripheral cortex as seen in Patient no. 2. Accordingly, although the diagnoses of multicystic dysplastic kidney and polycystic kidney disease were considered in Patients no. 1 and no. 2, respectively, it is more likely that the cystic kidney malformations of our two patients represent previously undescribed anomalies associated with the Robinow syndrome. The absence of vertebral anomalies and the presence of forearm brachymelia in our two patients suggest that both may have the autosomal dominant form of the syndrome as originally described by Robinow et al. (1969). The fact that the kidney is a recognized, albeit uncommonly affected organ in Robinow syndrome was noted in a recent extensivereview of the literature by Butler & Wadlington (1987). They identified four of 14 (29%) patients with a renal anomaly of an undefined nature. It is difficult to define the pathogenesis of the cystic changes observed in our patients with Robinow syndrome without tissue available for morphologic evaluation. It is possible that the dysplastic lesions result from altered nephrogenesis and reflect embryonic maldevelopment early in gestation. The asymptomatic renal cysts may arise as
a disturbance of nephrogenesis towards the end of pregnancy. Finally, as with all syndromes which have not been defined by either a biochemical marker or a specific gene mutation, such as Robinow syndrome, it is difficult, if not impossible, to define a phenotype characteristic of the syndrome. Thus, the possibility that the malformations noted in our patients represent a previously undescribed syndrome must also be considered.
References Ault B. H., E. Burton & F. B. Stapleton (1988). Cystic kidneys in infants: a brighter outlook. Contemp. Ped. Oct, 122-136. Bain M. D., R. M. Winter & J. Burn (1986). Robinow syndrome without mesomelic brachymelia: a report of five cases. J . Med. Genet. 23,350-354. Bernstein J., A. J. Brough & A. J. McAdams (1974). The renal lesion in syndromes of multiple congenital malfonnations. Birth Defects: Original Article Series. X. 4. pp. 35-43. Butler M. G. & W. B. Wadlington (1987). Robinow syndrome: report of two patients and review of literature. Clin. Genet. 31, 77-85. Lee P. A., C. J. Migeon, T. R. Brown & M. Robinow (1982). Robinow’s syndrome: partial primary hypogonadism in pubertal boys, with penistena of micropenis. Am. J. D b . Child. 136,327-330. Portnoy Y. (1979). Robinow syndrome. Clin. Pedial. IS. 707-708. Robinow M., F. N. Silverman & H. 0. Smith (1969). A newly recognized dwarfing syndrome. Am. J. Dis. Child. 117,645-651. Shprintzen RJ, R. B. Goldberg, P. Saenger & E. J. Sidoti (1982). Male-to-male transmission of Robinow’s syndrome: its occurrence in association with cleft lip and cleft palate. Am. J . Dis. Child. 136, 594-597. Address: Bradley A . Warady, M.D. Nephrology Section The Children’s Mercy Hospital 24th and Gillham Kansas City, Missouri 64108 USA
Clinical Genetics 1990: 37: 481-484
Robinow syndrome: report of two patients with cystic kidney disease LYNNWIENS,D. K. STRICKLAND, BARBARA SNIFFENAND BRADLEYA. WARADY The Children’s Mercy Hospital, Kansas City, Missouri, USA Two patients with Robinow syndrome and cystic kidney disease are described. We propose that this anomaly should be added to the spectrum of malformations associated with the syndrome. Received 20 June, revised 7 December, accepted f o r publirarion 9 December 1989 Key words: cyst; dysplasia; kidney; Robinow syndrome.
Robinow syndrome (fetal face syndrome) is a rare entity first described in 1969. It is characterized by a spectrum of anomalies including mesomelic brachymelia, hemivertebrae, frontal bossing, hypertelorism, brachydactyly, cleft lip/palate, scoliosis, depressed nasal bridge, short stature and genital hypoplasia (Robinow et al. 1969, Portnoy 1979, Lee et al. 1982, Shprintzen et al. 1982). Cystic kidney disease is a previously undescribed finding in such patients. We have cared for two unrelated children with Robinow syndrome and cystic kidney disease. Patient 1 SR., a S-month-old white male infant, was admitted to The Children’s Mercy Hospital for evaluation of cystic kidney disease, tachypnea and generalized duskiness. This patient’s prenatal course was complicated by maternal hypertension and intrauterine growth retardation. A prenatal ultrasound revealed a possible cystic left kidney. The family history was negative for renal disease. An amniocentesis was per-
formed at 20 weeks of gestation and revealed a 46,XY karyotype. No fetal growth was reported during weeks 31 and 32 of pregnancy. Prompted by maternal hypertension an elective cesarean section was performed at 33 weeks of gestation. Findings on initial physical examination included hypertelorisrn, long philtrum, low set ears, bilateral cryptorchidism, micropenis, short forearms and brachydactyly, all felt to be compatible with the diagnosis of Robinow syndrome. There were no vertebral anomalies. Additional findings included a well-delineated left lower quadrant abdominal mass and an anteriorly displaced anus. Radiologic evaluation included an abdominal plain film which revealed a markedly distended cecum and the absence of air in the rectum. A barium enema established the diagnosis of malrotation with anal stenosis. A renal ultrasound was performed at 2 weeks of age and revealed a normal right kidney and a small left kidney with multiple nontommunicating cysts and increased echogznicity in the non-cystic areas. The serum creatinine was 0.3 mg/dl at the time of discharge from the newborn nursery.
482
WlENS ET A L
Upon hospital admission at age 5 months, the most prominent findings on physical examination included the patient’s short stature (height and weight less than the 5th percentile) as well as the craniofacial and extremity abnormalities characteristic of Robinow syndrome. In addition, the patient demonstrated a generalized dusky appearance, a Grade I/VI systolic murmur heard best at the left midsternal border, and hepatomegaly with the liver edge palpable 5 cm below the right costal margin. Laboratory data demonstrated the following: BUN 20 mg/dl, creatinine 0.9 mg/dl, urinalysis: specific gravity 1.010, 1+ protein, 0-2 WBC/HPF. A renal ultrasound was performed and confirmed the previous ultrasound findings (Fig. 1). Nuclear renal scintography with technetium-99m diethylenetriamine penta-acidic acid (Tc-99m-DTPA) demonstrated the absence of uptake OF the
left side and normal uptake on the right. Cardiac catheterization was performed and revealed pulmonary hypertension. This was felt to be secondary to idiopathic alveolar hypoventilation and was managed with oxygen, furosemide and digoxin. Patient 2
LV, a 4-year-old Hispanic female, was admitted to The University of Kansas Medical Center for evaluation of a 3-4 cm left upper quadrant abdominal mass noted on routine physical examination. The diagnosis of Robinow syndrome had been made at 6 months of age. The patient had congenital hip dislocation which was treated by abduction splints. A patent ductus arteriosus was treated by surgical lig ation at age 2 years. There was no previous history of hypertension or urinary tract in-
483
R O B IN O W S Y N D R O M E
fections, nor was there a family history of kidney disease. Physical examination revealed a thin, petite individual with features characteristic of Robinow syndrome. These included short stature (height and weight less than the 5th percentile), mesomelic brachymelia, hypertelorism, wide palpebral fissures, short upturned nose, triangular shaped mouth and micrognathia. There were no vertebral anomalies. In addition, both kidneys were enlarged and easily palpable. Laboratory data revealed the following values: BUN 21 mg/dl, creatinine - 0.3 mg/dl and creatinine clearance - 106 ml/min/1.73 m2. A renal ultrasound study identified mild to moderately enlarged kidneys with increased echogenicity throughout the cortex and medulla. Multiple macroscopic cysts were present in both kidneys, being most prominent in the upper pole of the right
kidney in the cortical region (Fig. 2). An intravenous pyelogram demonstrated bilaterally enlarged kidneys. A renal scan with Tc 99m DTPA demonstrated prompt and symmetrical blood flow to both kidneys. Split renal functions were 58% on the right and 42% on the left. An abdominal ultrasound did not identify hepatic cysts. Renal ultrasounds of both parents revealed kidneys of normal size, shape and configuration without evidence of cysts. Discussion
The characteristic features of Robinow syndrome include facial anomalies (hypertelorism, anteverted nares, broad nasal bridge, macrocephaly, frontal bossing, long philtrum, cleft lip/palate), musculoskeletal anomalies (short stature, vertebral anomalies, scoliosis, inguinal and umbilical her-
Fig. 2. Renal ultrasound demonstrating moderately enlarged kidney with increased echogenicity in cortex and medulla and multiple cysts.
484
WIENS ET AL
nias), hypoplastic genitalia, and cryptorchidism (Robinow et al. 1969, Portnoy 1979, Lee et al. 1982, Shprintzen et al. 1982). The syndrome may be genetically heterogeneous with at least three recognized types (Robinow et al. 1969, Bain et al. 1986). We present two patients with Robinow syndrome and cystic kidney disease, an association which has not previously been reported. It is well recognized that the renal lesions associated with most multiple malformation syndromes are cystic in nature (Ault et al. 1988, Bernstein et al. 1974). The lesions are often poorly described and with an undefined natural history. They may range from severe cystic dysplasia, as seen in Patient no. 1, to asymptomatic microcysts and macrocysts localized to the peripheral cortex as seen in Patient no. 2. Accordingly, although the diagnoses of multicystic dysplastic kidney and polycystic kidney disease were considered in Patients no. 1 and no. 2, respectively, it is more likely that the cystic kidney malformations of our two patients represent previously undescribed anomalies associated with the Robinow syndrome. The absence of vertebral anomalies and the presence of forearm brachymelia in our two patients suggest that both may have the autosomal dominant form of the syndrome as originally described by Robinow et al. (1969). The fact that the kidney is a recognized, albeit uncommonly affected organ in Robinow syndrome was noted in a recent extensivereview of the literature by Butler & Wadlington (1987). They identified four of 14 (29%) patients with a renal anomaly of an undefined nature. It is difficult to define the pathogenesis of the cystic changes observed in our patients with Robinow syndrome without tissue available for morphologic evaluation. It is possible that the dysplastic lesions result from altered nephrogenesis and reflect embryonic maldevelopment early in gestation. The asymptomatic renal cysts may arise as
a disturbance of nephrogenesis towards the end of pregnancy. Finally, as with all syndromes which have not been defined by either a biochemical marker or a specific gene mutation, such as Robinow syndrome, it is difficult, if not impossible, to define a phenotype characteristic of the syndrome. Thus, the possibility that the malformations noted in our patients represent a previously undescribed syndrome must also be considered.
References Ault B. H., E. Burton & F. B. Stapleton (1988). Cystic kidneys in infants: a brighter outlook. Contemp. Ped. Oct, 122-136. Bain M. D., R. M. Winter & J. Burn (1986). Robinow syndrome without mesomelic brachymelia: a report of five cases. J . Med. Genet. 23,350-354. Bernstein J., A. J. Brough & A. J. McAdams (1974). The renal lesion in syndromes of multiple congenital malfonnations. Birth Defects: Original Article Series. X. 4. pp. 35-43. Butler M. G. & W. B. Wadlington (1987). Robinow syndrome: report of two patients and review of literature. Clin. Genet. 31, 77-85. Lee P. A., C. J. Migeon, T. R. Brown & M. Robinow (1982). Robinow’s syndrome: partial primary hypogonadism in pubertal boys, with penistena of micropenis. Am. J. D b . Child. 136,327-330. Portnoy Y. (1979). Robinow syndrome. Clin. Pedial. IS. 707-708. Robinow M., F. N. Silverman & H. 0. Smith (1969). A newly recognized dwarfing syndrome. Am. J. Dis. Child. 117,645-651. Shprintzen RJ, R. B. Goldberg, P. Saenger & E. J. Sidoti (1982). Male-to-male transmission of Robinow’s syndrome: its occurrence in association with cleft lip and cleft palate. Am. J . Dis. Child. 136, 594-597. Address: Bradley A . Warady, M.D. Nephrology Section The Children’s Mercy Hospital 24th and Gillham Kansas City, Missouri 64108 USA
