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Hypogonadotrophic Hypogonadism, and Cerebellar J Med Genet: First Published As 10.1136/Jmg.34.9.767 on 1 September 1997

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Hypogonadotrophic Hypogonadism, and Cerebellar J Med Genet: First Published As 10.1136/Jmg.34.9.767 on 1 September 1997 J7Med Genet 1997;34:767-771 767 Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar J Med Genet: first published as 10.1136/jmg.34.9.767 on 1 September 1997. Downloaded from ataxia: Boucher-Neuh'auser syndrome P Rump, B C J Hamel, A J L G Pinckers, P A van Dop Abstract years because of slowly progressive visual We describe two sibs with chorioretinal problems consisting of night blindness and dystrophy, hypogonadotrophic hypogo- constricting visual fields. His visual acuity was nadism, and cerebellar ataxia, Boucher- 5/10 in both eyes. Intraocular pressure was 17 Neuhauser syndrome, a rare but distinct mmHg on the right and 18 mmHg on the left. pleiotropic single gene disorder with an Fundoscopy showed bilateral atrophy of the autosomal recessive pattern of inherit- retinal pigment epithelium and choriocapillaris ance. The cases presented illustrate that in the mid peripheral areas, with peripapillary this syndrome is still poorly recognised. atrophy and retinal pigment epithelium altera- We provide a review and analysis of previ- tions of the maculae. The electro-oculogram ously reported cases and the differential was disturbed bilaterally while electroretinog- diagnosis, which might aid in the identifi- raphy showed no photopic or scotopic re- cation of additional cases. sponses at all. A fluorescein angiogram indi- (7Med Genet 1997;34:767-771) cated central choriocapillaris atrophy. Colour discrimination was not disturbed. The diagno- Keywords: Boucher-Neuhauser syndrome; ataxia; hy- pogonadism; chorioretinal degeneration sis of choroideremia was suggested. At 25 years of age, he was examined because of poor sexual development. He never needed In 1969, Boucher and Gibberd' described two to shave and although he had erections on sisters with "a combination of several features awakening no ejaculation occurred. His height which although frequently occurring alone or was 178 cm (25th centile) and weight 65 kg in pairs, rarely occur all in one patient". The (25th centile). Compared to his trunk, he had features referred to are chorioretinal degenera- relatively long limbs. There was sparse pubic tion, hypogonadism, and ataxia, which at that and normal axillary hair with absent chest and time did not "conform to any of the recognised facial hair. There was no gynaecomastia and he http://jmg.bmj.com/ syndromes". had a normal masculine voice. He had a very Six years later, Neuhauser and Opitz2 small scrotum and his penis and testicles were described a new autosomal recessive syndrome small but without anatomical abnormalities. Department of Human combining hypogonadotrophic hypogonadism Laboratory tests, including a complete blood Genetics, University and cerebellar ataxia. Although ophthalmologi- count, routine blood chemistry profile, and Hospital Nijmegen, PO cal examination of two patients described in urine analysis, were within normal limits. Box 9101, 6500 HB Nijmegen, The this study showed retinal pigmentary changes Endocrinological studies disclosed hypogona- on September 24, 2021 by guest. Protected copyright. Netherlands and atrophy, these findings were not consid- dotrophic hypogonadism. The serum level of P Rump ered to be part of the syndrome. The similari- testosterone was extremely low (0.86 nmol/l, B C J Hamel ties between the cases reported by them and normal 10-35) and the concentrations of those reported by Boucher and Gibberd' were luteinising hormone (LH) and follicle stimulat- Department of therefore not recognised until 1989 when Lim- ing hormone (FSH) were below the lowest Ophthalmology, University Hospital ber et al,3 on re-evaluation of one ofthe patients detectable level (<1.0 mIU/ml). There was no Nijmegen, PO Box described by Neuhauser and Opitz,2 suggested response to a single intravenous dose of LH 9101, 6500 HB that this was a specific pleiotropic single gene releasing hormone (LH-RH) even after re- Nijmegen, The disorder and named it Boucher-Neuhauser peated stimulation with LH-RH for one week, Netherlands syndrome. suggesting an abnormal pituitary function. The A J L G Pinckers So far, 17 cases from nine families have been serum levels of oestradiol, cortisol, prolactin, Department of reported, only three of these families in genetic thyroid stimulating hormone (TSH), and Gynaecology and publications.>' In the present study, we thyroxine (T4) were, however, all normal. Bone Obstetrics, Catharina describe two additional cases and after review- age, determined according to Greulich and Hospital, PO Box 1350, ing the published reports list the main clinical Pyle, was 15 years 6 months. He was treated 5602 ZA Eindhoven, characteristics of this rare syndrome and its with intramuscular hormone injections (250 The Netherlands differential diagnosis. P A van Dop mg testosterone enantate (TestovironC©) every four weeks). Subsequently, secondary sex Correspondence to: Case reports characteristics appeared. There was marked Dr Hamel. CASE 1 increase in facial and pubic hair growth and The proband, a 31 year old male, was born ejaculation occurred. Since the Received 10 January 1997 site of the hor- Revised version accepted for after a normal pregnancy and delivery. He was mone injections was troubling the patient, the publication 21 March 1997 seen by an ophthalmologist at the age of 23 injections were replaced by oral therapy (testo- 768 Rump, Hamel, Pinckers, van Dop sterone undecanoate (AndriolC), 80 mg/day) retinitis pigmentosa (NARP) at position 8993 after five years. were also excluded. At the age of 30 years, an ophthalmological The patient was treated with an oral contra- J Med Genet: first published as 10.1136/jmg.34.9.767 on 1 September 1997. Downloaded from re-evaluation was performed at our clinic. At ceptive (Trisequens(©) and within three years that time, his best corrected visual acuity was of therapy breast development and pubic hair right 1/10 and left 5/10. The cornea, anterior growth both reached Tanner stage 5. The segment, lens, and vitreous were normal. Ocu- internal sexual organs however remained small lar motility and pupillary responses were not and on temporary discontinuation of disturbed. His eyelashes were relatively long. medication no menstrual periods occurred. Fundoscopy showed choroidal atrophy in the At the age of 24 years an ophthalmological peripapillary region, small retinal vessels, pink evaluation was performed because she had coloured optic discs, and bone spicule-like noted that in the past three years her visual clumps of pigment deposition, together with fields had narrowed progressively. Her best atrophy of the retinal pigment epithelium and corrected visual acuity was right 5/10 and left choriocapillaris in the mid peripheral areas. 5/10. Slit lamp examination of the anterior seg- Intraocular pressure was normal in both eyes. ments showed no abnormalities. Like her On electroretinography some photopic rest brother, she had relatively long eyelashes. Fun- activity was seen while the electro-oculogram doscopy showed atrophic retinal pigment was flat. Colour vision examination showed a epithelium alterations, narrow retinal vessels, combined blue-yellow and red-green defect and bone spicule-like clumps of pigment depo- with anomaloscopic diminished red sensitivity. sition, very similar to the fundoscopic findings Goldmann perimetry showed a large temporal of her brother. On electoretinography some scotoma and a decrease of central sensitivity photopic rest activity was seen and the electro- bilaterally. The diagnosis of atypical chorioreti- oculogram was flat. Colour vision examination nal dystrophy was made. The diagnosis of showed a blue-yellow defect with anomalo- choroideremia was rejected because of the fun- scopic diminished red sensitivity. Visual field doscopy results and because his mother did not testing on a Goldmann perimeter showed a have fundoscopic signs of a choroideremia car- large ring scotoma and loss of central sensitiv- rier. ity bilaterally. The diagnosis was atypical chorioretinal dystrophy. Since both brother and sister suffered from CASE 2 hypogonadotrophic hypogonadism and retinal The proband's younger sister was born after a degeneration, an inherited syndrome combin- normal pregnancy and delivery. She was first ing these two conditions had to be considered. seen for primary amenorrhoea and poor sexual Boucher-Neuhauser syndrome was a likely development at 21 years of age. On examin- candidate. Therefore, an extensive ation she was 175 cm (80th centile) in height neurological evaluation of both patients was and 58 kg (50th centile) in weight. Breast performed. Both the proband and his sister development was poor (Tanner 1-2) and only reported a slight disturbance of balance, first sparse pubic hair was present. Gynaecological occurring during childhood. On examination a http://jmg.bmj.com/ examination showed hypoplastic external disturbed balance and gait was evidently sexual organs. The vagina and cervix were very present in both patients. Furthermore, marked small and the uterus and adnexal structures dysdiadochokinesis of the hands and an ataxic were clinically undetectable. A complete blood heel to shin test was found. Neither patient was count and routine blood chemistry profile able to walk on their heels, suggesting some showed no abnormalities. Endocrinological degree of muscle weakness. The deep tendon studies, however, showed hypogonadotrophic reflexes were just elicitable or absent and there on September 24, 2021 by guest. Protected copyright. hypogonadism. The serum level of oestradiol
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