American Journal of M e d i c a l Genetics 44:369-373 (1992)
Brief Clinical Report Case of Ovarian Dysgenesis and Dilated Cardiomyopathy Supports Existence of Malouf Syndrome KoYji Narahara, Masahiro Kamada, Yukio Takahashi, Kazushiro Tsuji, YYji Yokoyama, Shinsuke Ninomiya, and Yoshiki Seino Department of Pediatrics, Okayama University Medical School, Okayama, Japan We describe an 18-year-old girl with ovarian dysgenesis, dilated cardiomyopathy, mild mental retardation, broad nasal base, blepharoptosis, and minor skeletal abnormalities. This unusual association of manifestations was f i s t reported by Malouf et al. [19851. Our patient, although a sporadic case, supports the existence of Malouf syndrome. 0 1992 Wiley-Liss, Inc.
KEY WORDS: ovarian dysgenesis, dilated cardiomyopathy, blepharoptosis, mental retardation, Malouf syndrome INTRODUCTION In 1985,Malouf et al. reported on 2 sisters with hypergonadotropic hypogonadism, dilated cardiomyopathy, blepharoptosis, and broad nasal base. It has been challenged whether this truly represents a new syndrome [Witt, 19873. We describe a girl with similar clinical manifestations and provide details on pathological findings at autopsy. CLINICAL REPORT This 18s/i2-year-oldgirl was admitted for dyspnea on exertion, orthopnea, and oliguria. She was born a t term as the second child to a 28-year-old mother and a 33year-old nonconsanguineous father. Birth weight was 2,600 g. Pregnancy and delivery were uneventful. The parents and the older sib were in good health. The patient’s development was mildly retarded she sat withReceived for publication December 31, 1991; revision received March 30, 1992. Address reprint requests to K. Narahara, M.D., Department of Pediatrics, Okayama University Medical School, 2-5-1 Shikatacho Okayama 700,Japan. 0 1992 Wiley-Liss, Inc.
out support a t 8 months, walked alone at 2 years, and said meaningful words at 21/12 years. Generalized convulsions related to febrile illnesses occurred several times a year since the age of i?i3/i2 years. Electroencephalography demonstrated paroxymal epileptic discharges in the left frontoparietal region. Seizures were well controlled with phenytoin and barbiturate after the age of €i7/12 years. She attended a school for special education. Chest film a t age 13 years showed mild cardiomegaly, for which no specific treatment was given. She had not yet menstruated a t the time of hospitalization. On admission her height was 162.3 cm (+1.1 SD), weight 44.0 kg (-1.2 SD), and head circumference (OFC) 53.0 cm ( - 1.7 SD).A Marfanoid habitus was evident, with an arm span of 164.8 cm and an upper-tolower segment ratio of 0.99. The heart rate was llO/min, respiratory rate 36/min, and blood pressure 98/76 mm Hg. She had mild exophthalmos, blepharoptosis, a broad nasal base, arachnodactyly, and mild thoracic scoliosis with a convexity to the right (Fig. 1).Auscultation of the heart showed an accentuated 3rd sound a t the apex but no murmurs. Her pubertal stage was classified as P l B l according to Tanner, and bone age was assessed as 13 years. Endocrine studies showed undetectable levels of serum estradiol and estriol, with very high basal FSH and LH levels, and with an exaggerated LH response after stimulation by LH-RH (Fig. 2), being in agreement with hypergonadotropic hypogonadism. Ophthalmological examination showed bilateral myopia. The acoustic brainstem response was normal. Chest film demonstrated marked cardiomegaly with a cardiothoracic ratio of 0.64. Electrocardiography(ECG)demonstrated left axis deviation, mitral P wave, complete right bundle branch block, prolonged QT interval, and inverted T waves on the I, L and V1 to V6 leads. M-mode echocardiography showed remarkable dilatation of the left atrium and ventricle, reduced left ventricular fractional shortening, and decrease in the opening of the mitral valve with abnormal closure (Fig. 3). The ventricular septum and posterior free wall were of normal thickness, but the
370
Narahara et al.
z
f
100
\ 100
50
50
z=
\
aE
w
-#
33 Q)
5
$j
I
2 E
5
10
0
30
90
60
10
120
30
0
Time after LH-RH (min)
60
90
120
Time after LH-RH (min)
Fig. 2. Changes in serum LH and FSH levels after stimulation by LH-RH. Shadowed areas indicate normal ranges of LH and FSH. Fig. 1. Patient at age 18 years.
d w rh -s,+-v.41/.-
-
w ~
F
7
,
~
v .
~
v ~
,
+
Fig. 3. M-mode echocardiographic scan. Ao: aorta, L A left atrium,MV: mitral valve, LV: left ventricle, IVS: interventricular septum, LVPW left ventricular posterior wall. Arrows indicate abnormal closures of the mitral valve.
systolic thickening of the posterior free wall was impaired. All of these findings were consistent with the diagnosis of left-side dilated cardiomyopathy and congestive heart failure. She had normal chromosomes (46, XX). Results of other laboratory investigations including a complete blood count, blood chemistry, PPD skin test, Wassermann reaction, and tests for autoantibodies were all normal. ECGs obtained in both parents and the older sister were normal. Despite the administration of digoxin, diuretics, and anticoagulant, the patient's congestive heart failure failed to improve, and she died 4 months later, at age 19Viz years. On autopsy her heart weighed 460 g. There was
marked dilatation of the atria and ventricles bilaterally. A thrombus was present in the left ventricle. The right ventricular free wall was 0.4 cm thick and the left 0.9 cm. Liver, kidneys, and lungs were congested. Vagina, uterus, and fallopian tubes were hypoplastic, and ovaries could not be identified on gross inspection. The myocardium was characterized histologically by diffuse cellular degeneration and interstitial fibrosis with no evidence of inflammation (Fig. 4a,b). There was no degeneration of the elastic fibers in the media of the aorta. Histologically, the apparent gonadal tissue consisted only of stromal cells and Mullerian tube remnants, with virtually absent oocytes (Fig. 4c, d).
-
Fig. 4. Histology of the myocardium (aand b) and the ovary (c and d). Hematoxylin and eosin stain 150). An arrow indicates a Mullerian remnant, and an arrowhead the only primary follicle left in the ovary. (x
372
Narahara et al.
DISCUSSION The association of gonadal dysgenesis with cardiomyopathy is rare. A literature review showed a total of 16 patients: 5 families including 10 males and 2 females [Najjar et al., 1973, 1984; Sacks et al., 1980; Malouf et al., 1985; Warren et al., 19871 and 4 isolated patients (3 females and one male) [Battiste et al., 1977; Fatourechi et al., 1982; Alfonso et al., 1988; and the present report]. Clinical findings in these patients are summarized in Table I. The families of the 10 male patients could be divided into 3 distinct clinical groups. The first group consisted of the 5 males in the 2 families reported by Najjar et al. [1973,19841. They had microtestes and very small phallus with or without hypospadias, early-onset cardiomyopathy, and mental retardation. The second group comprized the 3 brothers with adult-onset cardiomyopathy, small testes, and collagenoma [Sacks et al., 19801.The third group consisted of 2 males with such metabolic abnormalities as diabetes mellitus, hypertriglyceridemia, and hyperuricemia, in addition to cardiomyopathy and testicular dysgenesis [Warren et al., 19871. The 2 females described by Malouf et al. [19851 showed the same clinical manifestations as found in our patient, except for the mental retardation and minor skeletal abnormalities. The characteristic facial changes of these patients consisted of blepharoptosis and a broad nasal base. The dilated cardiomyopathy preferentially affected the left ventricle. The onset of cardiovascular symptoms occurred during the late teens or the early twenties. The endocrine findings of these patients were similar, and histologic evaluation indicated dysgenetic ovary with an absence of oocytes. This
phenotypic similarity strongly suggests that the patients of Malouf et al. [19851 and the one in our report had the same syndrome. The presence of mental retardation and minor skeletal abnormalities in our patient may represent component manifestations of this syndrome or coincidence. Noonan syndrome is the most important condition to be considered in the differential diagnosis of the Malouf syndrome. It has been argued that the clinical manifestations of the latter were compatible with a diagnosis of Noonan syndrome [Witt, 19871. Although the facial findings of the patients with Malouf syndrome are shared by those with Noonan syndrome, many cardinal findings in the latter such as short stature, hypertelorism, ear malformations, webbed neck, and thorax abnormalities are absent in Malouf syndrome [Der Kaloustian, 19871. Moreover, the cardiac and gonadal findings in Noonan syndrome are quite different from those of Malouf syndrome. The cardiac anomalies specific to Noonan syndrome include pulmonary valve stenosis, which can be accompaniedby atrial septal defect,patent ductus arteriosus, ventricular septal defect, or branch stenosis of the pulmonary arteries, and asymmetrical septal hypertrophy [Mendez and Opitz, 19851. Furthermore, normal gonadal function is the rule in females with Noonan syndrome [Aarskog, 19811. The pathogenesis of the cardiomyopathy in Malouf syndrome is unknown. This syndrome seems to be inherited as an autosomal recessive trait. It has been suggested that males with this syndrome may have cardiomyopathy but not testicular dysgenesis [Malouf et al., 19851.This may be compared to Perrault syndrome, in which the female homozygotes have both deafness and ovarian dysgenesis, whereas the male homozygotes
TABLE I Clinical Findings of the Previously &ported Patients with Gonadal Dssgenesis and CardiomvoDathv a Sex of patients Age at examination
C
d
3M + 2M 0-12 y
3M 29-48 y
1M 23y
e 2F 20-26y
46,XY
46,XX
46,XY
46,XY
46,XX
2M 36-37 Y 46,XY
-
+-
Karyotype Mental retardation Deafness Short stature Ptosis Prominent nasal base Small mandible Webbed neck Kyphoscoliosis Joint abnormality Arachnodactyly Ovarian dysgenesis Small testes Micropenis Cryptorchidism Cardiomyopathy
+ or-
Increased LH level Increased FSH level Collagenoma Diabetes mellitus
+ or-
.Najjar et al. 11973, 19841. bBattiste et al. [19771. ‘Sacks et al. [19801.
f
b 1F 14 Y
-
-
-
ND ND
+
+ + +-
-
I
Polycystic
+
+
+ or +
-
-
-
++
-
-
+
-
+ ND +
-
+-
I
I
-
I I I
+ -
Hypertrophic ND ND
Dilated
-
-
-
+to +to
+-
++ ++
:Fatomechi et al. [19821. Malouf et al. [19851. ‘Warren et al. [19871.
+ + +
Hypertrophic -
-
+ +-
-
+
-
h 1F 18 Y
46,XY
46,XX
-
+
I I I
I I I
-
+
I
+
I I I
ND
Dilated
Dilated
++
+ +-
++
g 1F 61 Y
I
+ gAlfonso et al. [19881. hPresent patient. ‘Not documented.
+ Hypertrophic ND ND -
+ Dilated
++ +-+
Ovarian Dysgenesis and Cardiomyopathy
373
Hypergonadotropic hypogonadism with congestive cardiomyopahave only the deafness [Pallister and Opitz, 19791. thy: An autosomal-recessive disorder? Am J Med Genet 20: Therefore, this syndrome should be always kept in mind 483-489. in the Of cardiomYoPathY Mendez m M , Opik JM (1985): Noonan syndrome: A review, Am J among adolescents and young adults. Med Genet 21:493-506. Najjar SS, Der Kaloustian VM, Nassif SI (1973): Genital anomaly, mental retardation, and cardiomyopathy: A new syndrome? J Pediatr 83:286-288. Aarskog D (1981):Dysmorphic syndromes. In Brook CGD (ed): “Clini- ~ a jss, j D~~ ~ Kaloustian ~ VM, Ardati KO (1984):Genital anomaly and cal Paediatric Endocrinology.” Oxford Blackwell, pp 167-169. cardiomyopathy: A new syndrome. Clin Genet 26:371-373. *lf0nso AYuO ci Renedo G, ReY M, Farre J, McKenna wJ (lg80 Pallister PD, Opitz JM (1979): The Perrault syndrome: Autosomal Sudden death in hypertrophic cardiomyopathy associated with 46, recessive ovarian dysgenesis with facultative, non-sex-limited senXY pure gonadal dysgenesis. Am Heart J 116:1099-1101. sorineural deafness. Am J Med Genet 4:239-246. Battiste CE,Feldt RH, Lie J T (1977): Congestive CardiOmYoPathY in Sacks HN, Crawley IS, Ward JA, Fine RM (1980): Familial cardioNoonan’s syndrome. Mayo Clin Proc 52561-664. myopathy, hypogonadism, and collagenoma. Ann Intern Med 93: Der Kaloustian VM (1987): Hypergonadotropic hypogonadism with 813-817. congestive cardiomyopathy (rejoiner). Am J bled Genet 2 6 Warren SE, S h n i t t s, Bauman M , Gianelly RE, Landsberg L, Baim 983-985. D S (1987):Late onset dilated cardiomyopathy in a unique familial syndrome of hypogonadism and metabolic abnormalities. Am Heart Fatourechi V, Sheikhzadeh AH, Gavam M (1982):Obstructive cardiomyopathy in a male dwarf with cryptorchidism. Clin Cardiol J 114:1522-1524. 5:301-303. Witt DR (1987): Hypergonadotropic hypogonadism with congestive cardiomyopathy (letter to the editor). Am J Med Genet 26983. Malouf J, Alam S, Kanj H, Mufarrij A, Der Kaloustian VM (1985):
REFERENCES
Fi
Brief Clinical Report Case of Ovarian Dysgenesis and Dilated Cardiomyopathy Supports Existence of Malouf Syndrome KoYji Narahara, Masahiro Kamada, Yukio Takahashi, Kazushiro Tsuji, YYji Yokoyama, Shinsuke Ninomiya, and Yoshiki Seino Department of Pediatrics, Okayama University Medical School, Okayama, Japan We describe an 18-year-old girl with ovarian dysgenesis, dilated cardiomyopathy, mild mental retardation, broad nasal base, blepharoptosis, and minor skeletal abnormalities. This unusual association of manifestations was f i s t reported by Malouf et al. [19851. Our patient, although a sporadic case, supports the existence of Malouf syndrome. 0 1992 Wiley-Liss, Inc.
KEY WORDS: ovarian dysgenesis, dilated cardiomyopathy, blepharoptosis, mental retardation, Malouf syndrome INTRODUCTION In 1985,Malouf et al. reported on 2 sisters with hypergonadotropic hypogonadism, dilated cardiomyopathy, blepharoptosis, and broad nasal base. It has been challenged whether this truly represents a new syndrome [Witt, 19873. We describe a girl with similar clinical manifestations and provide details on pathological findings at autopsy. CLINICAL REPORT This 18s/i2-year-oldgirl was admitted for dyspnea on exertion, orthopnea, and oliguria. She was born a t term as the second child to a 28-year-old mother and a 33year-old nonconsanguineous father. Birth weight was 2,600 g. Pregnancy and delivery were uneventful. The parents and the older sib were in good health. The patient’s development was mildly retarded she sat withReceived for publication December 31, 1991; revision received March 30, 1992. Address reprint requests to K. Narahara, M.D., Department of Pediatrics, Okayama University Medical School, 2-5-1 Shikatacho Okayama 700,Japan. 0 1992 Wiley-Liss, Inc.
out support a t 8 months, walked alone at 2 years, and said meaningful words at 21/12 years. Generalized convulsions related to febrile illnesses occurred several times a year since the age of i?i3/i2 years. Electroencephalography demonstrated paroxymal epileptic discharges in the left frontoparietal region. Seizures were well controlled with phenytoin and barbiturate after the age of €i7/12 years. She attended a school for special education. Chest film a t age 13 years showed mild cardiomegaly, for which no specific treatment was given. She had not yet menstruated a t the time of hospitalization. On admission her height was 162.3 cm (+1.1 SD), weight 44.0 kg (-1.2 SD), and head circumference (OFC) 53.0 cm ( - 1.7 SD).A Marfanoid habitus was evident, with an arm span of 164.8 cm and an upper-tolower segment ratio of 0.99. The heart rate was llO/min, respiratory rate 36/min, and blood pressure 98/76 mm Hg. She had mild exophthalmos, blepharoptosis, a broad nasal base, arachnodactyly, and mild thoracic scoliosis with a convexity to the right (Fig. 1).Auscultation of the heart showed an accentuated 3rd sound a t the apex but no murmurs. Her pubertal stage was classified as P l B l according to Tanner, and bone age was assessed as 13 years. Endocrine studies showed undetectable levels of serum estradiol and estriol, with very high basal FSH and LH levels, and with an exaggerated LH response after stimulation by LH-RH (Fig. 2), being in agreement with hypergonadotropic hypogonadism. Ophthalmological examination showed bilateral myopia. The acoustic brainstem response was normal. Chest film demonstrated marked cardiomegaly with a cardiothoracic ratio of 0.64. Electrocardiography(ECG)demonstrated left axis deviation, mitral P wave, complete right bundle branch block, prolonged QT interval, and inverted T waves on the I, L and V1 to V6 leads. M-mode echocardiography showed remarkable dilatation of the left atrium and ventricle, reduced left ventricular fractional shortening, and decrease in the opening of the mitral valve with abnormal closure (Fig. 3). The ventricular septum and posterior free wall were of normal thickness, but the
370
Narahara et al.
z
f
100
\ 100
50
50
z=
\
aE
w
-#
33 Q)
5
$j
I
2 E
5
10
0
30
90
60
10
120
30
0
Time after LH-RH (min)
60
90
120
Time after LH-RH (min)
Fig. 2. Changes in serum LH and FSH levels after stimulation by LH-RH. Shadowed areas indicate normal ranges of LH and FSH. Fig. 1. Patient at age 18 years.
d w rh -s,+-v.41/.-
-
w ~
F
7
,
~
v .
~
v ~
,
+
Fig. 3. M-mode echocardiographic scan. Ao: aorta, L A left atrium,MV: mitral valve, LV: left ventricle, IVS: interventricular septum, LVPW left ventricular posterior wall. Arrows indicate abnormal closures of the mitral valve.
systolic thickening of the posterior free wall was impaired. All of these findings were consistent with the diagnosis of left-side dilated cardiomyopathy and congestive heart failure. She had normal chromosomes (46, XX). Results of other laboratory investigations including a complete blood count, blood chemistry, PPD skin test, Wassermann reaction, and tests for autoantibodies were all normal. ECGs obtained in both parents and the older sister were normal. Despite the administration of digoxin, diuretics, and anticoagulant, the patient's congestive heart failure failed to improve, and she died 4 months later, at age 19Viz years. On autopsy her heart weighed 460 g. There was
marked dilatation of the atria and ventricles bilaterally. A thrombus was present in the left ventricle. The right ventricular free wall was 0.4 cm thick and the left 0.9 cm. Liver, kidneys, and lungs were congested. Vagina, uterus, and fallopian tubes were hypoplastic, and ovaries could not be identified on gross inspection. The myocardium was characterized histologically by diffuse cellular degeneration and interstitial fibrosis with no evidence of inflammation (Fig. 4a,b). There was no degeneration of the elastic fibers in the media of the aorta. Histologically, the apparent gonadal tissue consisted only of stromal cells and Mullerian tube remnants, with virtually absent oocytes (Fig. 4c, d).
-
Fig. 4. Histology of the myocardium (aand b) and the ovary (c and d). Hematoxylin and eosin stain 150). An arrow indicates a Mullerian remnant, and an arrowhead the only primary follicle left in the ovary. (x
372
Narahara et al.
DISCUSSION The association of gonadal dysgenesis with cardiomyopathy is rare. A literature review showed a total of 16 patients: 5 families including 10 males and 2 females [Najjar et al., 1973, 1984; Sacks et al., 1980; Malouf et al., 1985; Warren et al., 19871 and 4 isolated patients (3 females and one male) [Battiste et al., 1977; Fatourechi et al., 1982; Alfonso et al., 1988; and the present report]. Clinical findings in these patients are summarized in Table I. The families of the 10 male patients could be divided into 3 distinct clinical groups. The first group consisted of the 5 males in the 2 families reported by Najjar et al. [1973,19841. They had microtestes and very small phallus with or without hypospadias, early-onset cardiomyopathy, and mental retardation. The second group comprized the 3 brothers with adult-onset cardiomyopathy, small testes, and collagenoma [Sacks et al., 19801.The third group consisted of 2 males with such metabolic abnormalities as diabetes mellitus, hypertriglyceridemia, and hyperuricemia, in addition to cardiomyopathy and testicular dysgenesis [Warren et al., 19871. The 2 females described by Malouf et al. [19851 showed the same clinical manifestations as found in our patient, except for the mental retardation and minor skeletal abnormalities. The characteristic facial changes of these patients consisted of blepharoptosis and a broad nasal base. The dilated cardiomyopathy preferentially affected the left ventricle. The onset of cardiovascular symptoms occurred during the late teens or the early twenties. The endocrine findings of these patients were similar, and histologic evaluation indicated dysgenetic ovary with an absence of oocytes. This
phenotypic similarity strongly suggests that the patients of Malouf et al. [19851 and the one in our report had the same syndrome. The presence of mental retardation and minor skeletal abnormalities in our patient may represent component manifestations of this syndrome or coincidence. Noonan syndrome is the most important condition to be considered in the differential diagnosis of the Malouf syndrome. It has been argued that the clinical manifestations of the latter were compatible with a diagnosis of Noonan syndrome [Witt, 19871. Although the facial findings of the patients with Malouf syndrome are shared by those with Noonan syndrome, many cardinal findings in the latter such as short stature, hypertelorism, ear malformations, webbed neck, and thorax abnormalities are absent in Malouf syndrome [Der Kaloustian, 19871. Moreover, the cardiac and gonadal findings in Noonan syndrome are quite different from those of Malouf syndrome. The cardiac anomalies specific to Noonan syndrome include pulmonary valve stenosis, which can be accompaniedby atrial septal defect,patent ductus arteriosus, ventricular septal defect, or branch stenosis of the pulmonary arteries, and asymmetrical septal hypertrophy [Mendez and Opitz, 19851. Furthermore, normal gonadal function is the rule in females with Noonan syndrome [Aarskog, 19811. The pathogenesis of the cardiomyopathy in Malouf syndrome is unknown. This syndrome seems to be inherited as an autosomal recessive trait. It has been suggested that males with this syndrome may have cardiomyopathy but not testicular dysgenesis [Malouf et al., 19851.This may be compared to Perrault syndrome, in which the female homozygotes have both deafness and ovarian dysgenesis, whereas the male homozygotes
TABLE I Clinical Findings of the Previously &ported Patients with Gonadal Dssgenesis and CardiomvoDathv a Sex of patients Age at examination
C
d
3M + 2M 0-12 y
3M 29-48 y
1M 23y
e 2F 20-26y
46,XY
46,XX
46,XY
46,XY
46,XX
2M 36-37 Y 46,XY
-
+-
Karyotype Mental retardation Deafness Short stature Ptosis Prominent nasal base Small mandible Webbed neck Kyphoscoliosis Joint abnormality Arachnodactyly Ovarian dysgenesis Small testes Micropenis Cryptorchidism Cardiomyopathy
+ or-
Increased LH level Increased FSH level Collagenoma Diabetes mellitus
+ or-
.Najjar et al. 11973, 19841. bBattiste et al. [19771. ‘Sacks et al. [19801.
f
b 1F 14 Y
-
-
-
ND ND
+
+ + +-
-
I
Polycystic
+
+
+ or +
-
-
-
++
-
-
+
-
+ ND +
-
+-
I
I
-
I I I
+ -
Hypertrophic ND ND
Dilated
-
-
-
+to +to
+-
++ ++
:Fatomechi et al. [19821. Malouf et al. [19851. ‘Warren et al. [19871.
+ + +
Hypertrophic -
-
+ +-
-
+
-
h 1F 18 Y
46,XY
46,XX
-
+
I I I
I I I
-
+
I
+
I I I
ND
Dilated
Dilated
++
+ +-
++
g 1F 61 Y
I
+ gAlfonso et al. [19881. hPresent patient. ‘Not documented.
+ Hypertrophic ND ND -
+ Dilated
++ +-+
Ovarian Dysgenesis and Cardiomyopathy
373
Hypergonadotropic hypogonadism with congestive cardiomyopahave only the deafness [Pallister and Opitz, 19791. thy: An autosomal-recessive disorder? Am J Med Genet 20: Therefore, this syndrome should be always kept in mind 483-489. in the Of cardiomYoPathY Mendez m M , Opik JM (1985): Noonan syndrome: A review, Am J among adolescents and young adults. Med Genet 21:493-506. Najjar SS, Der Kaloustian VM, Nassif SI (1973): Genital anomaly, mental retardation, and cardiomyopathy: A new syndrome? J Pediatr 83:286-288. Aarskog D (1981):Dysmorphic syndromes. In Brook CGD (ed): “Clini- ~ a jss, j D~~ ~ Kaloustian ~ VM, Ardati KO (1984):Genital anomaly and cal Paediatric Endocrinology.” Oxford Blackwell, pp 167-169. cardiomyopathy: A new syndrome. Clin Genet 26:371-373. *lf0nso AYuO ci Renedo G, ReY M, Farre J, McKenna wJ (lg80 Pallister PD, Opitz JM (1979): The Perrault syndrome: Autosomal Sudden death in hypertrophic cardiomyopathy associated with 46, recessive ovarian dysgenesis with facultative, non-sex-limited senXY pure gonadal dysgenesis. Am Heart J 116:1099-1101. sorineural deafness. Am J Med Genet 4:239-246. Battiste CE,Feldt RH, Lie J T (1977): Congestive CardiOmYoPathY in Sacks HN, Crawley IS, Ward JA, Fine RM (1980): Familial cardioNoonan’s syndrome. Mayo Clin Proc 52561-664. myopathy, hypogonadism, and collagenoma. Ann Intern Med 93: Der Kaloustian VM (1987): Hypergonadotropic hypogonadism with 813-817. congestive cardiomyopathy (rejoiner). Am J bled Genet 2 6 Warren SE, S h n i t t s, Bauman M , Gianelly RE, Landsberg L, Baim 983-985. D S (1987):Late onset dilated cardiomyopathy in a unique familial syndrome of hypogonadism and metabolic abnormalities. Am Heart Fatourechi V, Sheikhzadeh AH, Gavam M (1982):Obstructive cardiomyopathy in a male dwarf with cryptorchidism. Clin Cardiol J 114:1522-1524. 5:301-303. Witt DR (1987): Hypergonadotropic hypogonadism with congestive cardiomyopathy (letter to the editor). Am J Med Genet 26983. Malouf J, Alam S, Kanj H, Mufarrij A, Der Kaloustian VM (1985):
REFERENCES
Fi
