American Journal of Medical Genetics 16:237-241 (1983)

Perrault’s Syndrome in Two Sisters

Peter Bosze, Katalin Skripeczky, Magdolna Gaal, Andras Toth, and Janos Laszlo

Cytogenetic Laboratory of the Clinic of Obstetrics and Gynecology, Postgraduate Medical School (P. B., A. T , J. L.), 2nd Pediatric Department of the Semrnelweis Medical University (K. S.), and Department of Pathology, Institute for Medicine in Physical Education and Sport (M. G.), Budapest, Hungary

We report on two sisters with Perrault’s syndrome, i.e., autosomal recessive ovarian dysgenesis associated with sensorineural deafness. They were deaf-mute and of normal height with a few minor somatic anomalies. Both had streak gonads and an apparently normal female 46,XX chromosome constitution. The parents were apparently not consanguineous. The mother had normal hearing. Other relatives were not available for study. Epilepsy, which occurred in three relatives including one of the index patients, may have been inherited coincidentally from the mother’s family.

Key words: ovarian dysgenesis, autosomal recessive inheritance, sensorineural deafness, pleio- tropy, Perrault’s syndrome

INTRODUCTION

Since the first description of the syndrome of primary ovarian failure with severe sensorineural deafness in two sisters by Perrault et a1 [ 19511 (restudied by Josso et a1 [19631), three other pertinent sibships were reported. Pallister and Opitz [1979] reviewed the 14 known cases and concluded that this condition was an uncommon autosomal recessive trait with obligatory ovarian dysgenesis in female homozygotes and facultative deafness in male and female homozygotes.

We report on two sisters with Perrault’s syndrome both affected with deaf- mutism.

Received for publication February 6, 1983; revision received April 22, 1983.

Address reprint requests to Dr. PCter BBsze, Clinic of Obstetrics and Gynecology, Postgraduate Medical School, P.O. Box 112, H-1389 Budapest, Hungary.

0 1983 Alan R. Liss. Inc.

238 Bosze et a1

TABLE I. Anthropometric Measurements of the Patients

Measurement (cm) (cm)

Sitting height 81.4 85.1 Arm span 162.4 164 Upper limb length 70.8 73.7

Patient 1 Patient 2

Height 160.3 162.3

Lower limb length 92 93.1 Biacromial width 34.2 35.5 Bitrochanteric width 30.2 33.8 Chest width 24.5 28.1 Chest depth (A-P) 14.3 17 Chest circumference 75.4 84.8 Abdominal circumference 71.5 88 Trochanteric circumference 87.2 101 Forearm circumference 21.4 23 Thigh circumference 47.8 57.8 Weight was normal for height (46.5 kg) (62.5 kg)

PATIENT 1

F.K. was referred for investigation at 20 yr because of primary amenorrhea and sexual immaturity. She was born to a 17-yr-old healthy mother and a 25-yr-old healthy father after a 40-wk uncomplicated pregnancy and a normal delivery. Birth weight was 3,100 g and length was 57 cm. Her neonatal development was uneventful. Severe sensorineural deafness was first noted and diagnosed at 1 yr of age, and she lacked speech and pubertal development.

On examination she was a young woman of normal height with undeveloped breasts and sparse pubic and axillary hair. She had blue sclerae, a highly arched palate, lumbar spina bifida occulta, slightly retarded bone age. Urography showed no anomaly, she had no color blindness. Her external genitalia were slightly immature with narrow vagina and immature uterus. No ovaries were palpable. Blood pressure was 110/70 mm Hg. Anthropometric data are in Table I.

Thyroid function was normal. Serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were elevated on two occasions (FSH 82, 110 mU/ml; LH 76, 125 mU/ml, respectively). She had normal levels of prolactin and cortisol. The vaginal mucosa was atrophic. Urinary estrogen excretion was low; 17- ketosteroid output was normal.

Results of the other laboratory studies were normal; she had apparently normal chromosomes (46,XX).

External and middle ears were normal. Polytomography of the 0 s pyramidale showed no abnormalities. She had severe sensorineural deafness with mutism (Fig. 1).

PATIENT 2

F.E. was seen at 18 yr because of failure of menarche and sexual development. She was born at term after an uneventful gestation and delivery with a birthweight of 3,200 g and a length of 57 cm. Her 19-yr-old mother and 28-yr-old father were

Perrault’s Syndrome 239

HZ

10

0

10

20

30

LO

50

60

70

80

90

100

120

Fig. 1. detectable hearing in the left ear of patient 2 .

Audiogram: 0 , right ear of patient 1; x, left ear of patient I : A, right ear of patient 2. No

healthy when she was born. Neonatal course was normal. She had severe congenital sensorineural deafness and lacked speech development. At 16 yr she developed seizures; since then she has been treated successfully with anticonvulsive medication.

Examination revealed infantile female phenotype with normal height, undevel- oped breasts, and sparse pubic and axillary hair. Except for hearing loss and slight micrognathia, she was otherwise normal. Urography showed no anomaly. She had no color blindness and bone age matched chronologic age. She had slightly undeveloped female external genitalia with narrow vagina and immature uterus. Adnexae were not palpable. Blood pressure was 120180 mm Hg. Anthropometric data are in Table I.

External and middle ears were normal. Polytomography of the internal ears uncovered no structural abnormality. She had severe sensorineural deafness with mutism (Fig. I), but no spontaneous or positional nystagmus; no nystagmus was demonstrable after Hallpike caloric vestibular stimulation. Body posture reflexes were normal. Electroencephalography and neurologic examination showed no anomaly. She was of normal intelligence with performance I.Q. 89 (Snijders-Oomen Nonverbal Intelligence Scale).

Thyroid function was normal. Serum LH and FSH levels were increased on several occasions. She had normal serum levels of prolactin and cortisol. Cells from vaginal smear were atrophic; urinary estrogen output was low and 17-ketosteroid excretion was normal.

Results of all other laboratory tests were normal; serum and urine amino- acid levels were also normal. Chromosomes were of apparently normal (46,XX) constitution.

240 Bosze et a1

TABLE 11. Dermatoglyphics of Patients With Perrault's Syndrome

Patient 2 Patient 1 Right Left Right Left

WellRcpoRcpoU, u , wdlu, u. u , u. wcwell~cwellwcll WdlvWdlvWcWcWlpv Fingertip patterns

Triradius Finger Palmar Axial

6 6 10 9 dcba dcba dcba dcba t (1 tb t tb tth t

Main line termination/D .C .B .A. / 75 " 5 "2 75"5'1 975 "5 ' 75"5'1

Palmar pattern areas Hy ,Th + 1.II.III.IV. L'"'P0,OOL Lrad 0, OOL L'ddO, OOL AUO, OOL Maximal atd angle 59" 46 43 O 48

TRC 180 240 ARC 212 425

DERMATOGLYPHICS

Dermatoglyphics are shown in Table 11. The ridge count, particularly in patient 2 , was increased, which could be attributed to the increased frequency of high- intensity patterns. The terminations of the A main lines (1-2, 1, respectively) were unusual. Some of the characteristics resemble those found in 45,X subjects.

FAMILY STUDY

Family history was unremarkable; parents were apparently not consanguineous. Three individuals-patient 2, her mother, and a brother of the maternal grand- mother-had idiopathic epilepsy.

DISCUSSION

Our patients with infantile female phenotype, underdeveloped genitalia, primary amenorrhea, low estrogen secretion with atrophic vaginal smears, high serum levels of FSH and LH, normal chromosomes and sensorineural deaf-mutism evidently have Perrault's syndrome [Pallister and Opitz, 19791.

The severity of the ovarian lesion in the present sisters corresponds to that found in other women with Perrault's syndrome. This tinding supports the conclusion of Pallister and Opitz [ 19791 that the presence of streak gonads is an obligatory manifes- tation in female homozygotes.

Developmental anomalies other than hearing loss are uncommon in individuals with Perrault's syndrome. However, minor variants have been observed. We also observed a few anomalies such as blue sclerae, highly arched palate, and spina bifida occulta in patient 1, micrognathia and unusual whorl patterns on the fingertips with increased ARC+TRC values in patient 2.

On the basis of consanguinity in two families, normal parents, and lack of affected collateral relatives, Pallister and Opitz [ 19791 concluded that Perrault's syndrome is an autosomal recessive trait. In the present family the parents were

Perrault’s Syndrome 241

apparently not consanguineous. The father was healthy, the mother had epilepsy. For the study of hearing, relatives other than the mother and the index patients were not available; mother’s hearing was normal.

Hereditary nerve deafness occurs in a great variety of conditions such as hereditary nephritis, osseus deformities, inborn errors of metabolism, etc. None of the sisters had signs of osseus deformities, renal or other diseases, except epilepsy in patient 2. In this patient amino acids were measured in the plasma and urine; no pathological plasma concentration or output was found. Vestibular function was abnormal in this case. The precise connection between the nerve deafness and streak gonad syndrome is uncertain. Pallister and Opitz [ 19791 think that these two anomalies are pleiotropic manifestations of the same trait. Although the cause of the epilepsy in the present cases is not clear, its familial occurrence suggests that it is also genetically determined. It seems a coincidental manifestation in this family, increasing the probability of ascertainment.

ACKNOWLEDGMENTS

It is a pleasure to thank Dr. Eva Susa for the dermatoglyphic study, Dr. Ott6 G. Eiben for the anthropometric measurements, and Dr. Imre Lhszl6 for the polytomog- raphy of the ears. This study was supported by the Scientific Research Council, Ministry of Health, Hungary 09/5-121218 L.; 09/6-17/025 G .

REFERENCES

Bosze P, Laszl6 J (1979): The streak gonad syndrome. Obstet Gynecoi54:544-548. Josso N, deGrouchy 3, Frdzal J, Lamy M (1963): Le syndrome de Turner familial; Ctude de deux

families avec caryotypes XO et XX. Ann Pediatr (Paris) 10: 163-167. Pallister PD, Opitz JM: The Perrault syndrome (1979): Autosomal recessive ovarian dysgenesis with

facultative, non-sex-limited sensorineural deafness. Am J Med Genet 4:239-246. Perrault M, Klotz B, Housset E (1951): Deux cas de syndrome de Turner avec surdi-mutitt dans unc

m&me fratrie. Bull Mem Soc med Hop paris 16:79-84.

Edited by John M. Opitz