A case of Bardet-Biedl Syndrome with Hypogonadism

2,877 views

Published on

0 Comments
4 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,877
On SlideShare
0
From Embeds
0
Number of Embeds
78
Actions
Shares
0
Downloads
69
Comments
0
Likes
4
Embeds 0
No embeds

No notes for slide

A case of Bardet-Biedl Syndrome with Hypogonadism

  1. 1. PROF.DR.G.SUNDARAMURTHY’S UNIT DR.K.SENTHAMIZH SELVAN A CASE OF HYPOGONADISM
  2. 2. CASE DETAILS <ul><li>Balaji </li></ul><ul><li>23 years </li></ul><ul><li>Male </li></ul><ul><li>kancheepuram </li></ul>
  3. 3. CLINICAL PRESENTATION <ul><li>C/O delayed developmental milestones </li></ul><ul><li>C/O diminished vision since childhood </li></ul><ul><li>C/O poor development of genitalia </li></ul><ul><li>HISTORY OF PRESENT ILLNESS </li></ul><ul><li>----- patient had delay in attaining gross motor ,fine motor,psycho-social and language milestones </li></ul><ul><li>----- From the age of 5 years patient had visual disturbance ,which was progressive , not associated with </li></ul>
  4. 4. <ul><li>double vision,watering , pain or reddening of eyes </li></ul><ul><li>patient had poor school performance and he was a drop-out from 2 nd std. </li></ul><ul><li>lost interest in games ,toys and surroundings </li></ul><ul><li>He was not employed and did house hold activities . </li></ul><ul><li>At 22 years of age he presented with poorly developed genitals </li></ul><ul><li>no h/o penile erection,no early morning penile tumescence , no h/o ejaculation </li></ul>
  5. 5. <ul><li>Had normal development of facial, pectoral, axillary and pubic hair . </li></ul><ul><li>No h/o seizures </li></ul><ul><li>No h/o weakness of limbs </li></ul><ul><li>H/o snoring + </li></ul><ul><li>No h/o disturbances in sleep pattern. </li></ul><ul><li>No h/o chest pain ,palpitation, breathlessness </li></ul><ul><li>No significant fever history </li></ul>
  6. 6. <ul><li>PERINATAL HISTORY: </li></ul><ul><li>- no h/o drug intake by mother for any ailments </li></ul><ul><li>- no h/o fever or any other medical ailments during pregnancy </li></ul><ul><li>- born of normal ,vaginal delivery </li></ul><ul><li>- no h/o prolonged labor </li></ul><ul><li>- no h/o neonatal fever or seizures </li></ul>
  7. 7. <ul><li>FAMILY HISTORY : </li></ul><ul><li>- Born of a 2 degree consanguinous marriage </li></ul><ul><li>- other sibbling is normal </li></ul><ul><li>- no other member in the family is having similar complaints. </li></ul>
  8. 8. ON EXAMINATION <ul><li>Patient was </li></ul><ul><li>Conscious </li></ul><ul><li>Responding to oral commands </li></ul><ul><li>Afebrile </li></ul><ul><li>Hydration fair </li></ul><ul><li>Obese –BMI of 31kg/m^2 (ht =155 cms, wt=75 kg) </li></ul><ul><li>B/L gynaecomastia </li></ul>
  9. 10. <ul><li>Short neck </li></ul><ul><li>Ht : neck ratio of 14 </li></ul>
  10. 11. <ul><li>Poly dactyly </li></ul><ul><li>------ post axial </li></ul>
  11. 12. <ul><li>high arched palate </li></ul><ul><li>Facial ,axillary and pectoral hairs are present normally </li></ul><ul><li>no pallor </li></ul><ul><li>anicteric </li></ul><ul><li>No cyanosis </li></ul><ul><li>no clubbing </li></ul><ul><li>no significant generalised lymphadenopathy </li></ul><ul><li>no pitting pedal edema </li></ul>
  12. 13. <ul><li>Flat foot </li></ul>
  13. 14. <ul><li>BP: 110/80mmHg </li></ul><ul><li>Pulse: 84 /min ,regular </li></ul><ul><li>CVS: </li></ul><ul><li>S1,S2 + </li></ul><ul><li>nomurmur </li></ul><ul><li>RS: </li></ul><ul><li>NVBS + </li></ul><ul><li>no added sounds </li></ul><ul><li>P/A: </li></ul><ul><li>soft,no HSM, BS+ </li></ul>
  14. 15. <ul><li>GENITALIA: </li></ul><ul><li>small sized penis, </li></ul><ul><li>external urethral meatus normal, </li></ul><ul><li>both testicles small sized – in the scrotal sac </li></ul><ul><li>pubic hair distribution –normal </li></ul><ul><li>no varicocele </li></ul>
  15. 16. <ul><li>CNS : </li></ul><ul><li>conscious </li></ul><ul><li>responding to oral commands </li></ul><ul><li>subnormal IQ </li></ul><ul><li>divergent squint , vision – perception of </li></ul><ul><li>hand movements </li></ul><ul><li>pupils equally reacting to light </li></ul>
  16. 18. Optic fundus
  17. 19. Optic fundus
  18. 20. Ophthal opinion <ul><li>media clear </li></ul><ul><li>disc pallor </li></ul><ul><li>bony spicules like structures </li></ul><ul><li>consistent with </li></ul><ul><li>---- RETINITIS PIGMENTOSA </li></ul>
  19. 21. ENT EVALUATION <ul><li>--- B/L mild sensorineural hearing loss </li></ul>
  20. 22. <ul><li>No other cranial nerve involvement </li></ul><ul><li>motor system-N </li></ul><ul><li>sensory system-N </li></ul><ul><li>no cerebellar signs </li></ul><ul><li>no meningeal signs </li></ul>
  21. 23. problems <ul><li>developmental delay </li></ul><ul><li>learning disability </li></ul><ul><li>strabismus </li></ul><ul><li>retinitis pigmentosa </li></ul><ul><li>mild sensorineural hearing loss </li></ul><ul><li>obesity </li></ul><ul><li>poly dactyly </li></ul><ul><li>hypogonadism </li></ul>
  22. 24. INVESTIGATIONS <ul><li>Urine: </li></ul><ul><li>alb-nil </li></ul><ul><li>sug –nil </li></ul><ul><li>dep-1-2 pus cells </li></ul><ul><li>CBC: </li></ul><ul><li>Hb-10.4gms% </li></ul><ul><li>TC-6400cells/cumm </li></ul><ul><li>DC-P60/L38/E2 </li></ul><ul><li>ESR-4/10mm </li></ul><ul><li>RFT: </li></ul><ul><li>blood sugar-110mgs% </li></ul><ul><li>urea-38mgs% </li></ul><ul><li>serum creatinine-0.9mgs% </li></ul><ul><li>serum Na-144meq/dl </li></ul><ul><li>K-4.8meq/dl </li></ul>
  23. 25. <ul><li>LFT:T.bilirubin- 1.2mg/dl </li></ul><ul><li>direct-0.6mg/dl </li></ul><ul><li>SGOT-44IU/L </li></ul><ul><li>SGPT-86IU/L </li></ul><ul><li>SAP-108IU/L </li></ul><ul><li>T.protein-5.5gms/dl </li></ul><ul><li>s.albumin-3.8gms/dl </li></ul><ul><li>s.globulin-1.9gms/dl </li></ul><ul><li>LIPID PROFILE: </li></ul><ul><li>s.total cholesterol- 210mgs/dl </li></ul><ul><li>LDL-170mgs/dl </li></ul><ul><li>HDL-40mgs/dl </li></ul><ul><li>TGS-140mgs/dl </li></ul><ul><li>ECG- WNL </li></ul><ul><li>CHEST XRAY-NORMAL STUDY </li></ul>
  24. 26. <ul><li>ECHO : Normal study </li></ul><ul><li>USG ABDOMEN : liver : 13.5 cm,spleen: 11.5 cms </li></ul><ul><li>RK: 10.4×6.6cm </li></ul><ul><li>LK: 9.3×4.8cm </li></ul><ul><li>pancreas: normal </li></ul><ul><li>USG SCROTUM: Rt. Testis: 3×1.7×1.3cm parenchyma </li></ul><ul><li>Lt.testis: 3×2.1×1.6cm normal </li></ul><ul><li>cord,epididymis: normal </li></ul><ul><li>tunica sac: normal </li></ul>
  25. 27. MRI BRAIN
  26. 30. IMPRESSION <ul><li>---- partially empty sella with </li></ul><ul><li>compressed pituitary gland </li></ul>
  27. 31. HORMONAL ASSAY <ul><li>TSH -2.050 (0.27-4.20 mIU/ml) </li></ul><ul><li>LH- 7.090 (1.7-8.6mIU/ml) </li></ul><ul><li>FSH- 11.05 (1.5-12.4mIU/ml) </li></ul><ul><li>Growth hormone -2.8 (0.5-17 ng/l) </li></ul><ul><li>Prolactin -6.12 (4.04-15.2ng/ml) </li></ul><ul><li>Testosterone- 0.19 (0.26-11.2ng/ml) </li></ul>
  28. 32. KARYOTYPING <ul><li>------- done at IOG, Egmore </li></ul>
  29. 33. <ul><li>46,XY </li></ul>
  30. 34. FINAL DIAGNOSIS <ul><li>“ BARDET-BIEDL SYNDROME WITH A </li></ul><ul><li>PARTIALLY EMPTY SELLA( PRIMARY) </li></ul><ul><li>PRESENTING AS HYPOGONADISM” </li></ul>
  31. 35. <ul><li>  </li></ul><ul><li>J Med Genet 1999;36:437-446 doi:10.1136/jmg.36.6.437 </li></ul><ul><li>Original article </li></ul><ul><li>“ New criteria for improved diagnosis of Bardet-Biedl syndrome”: results of a population survey </li></ul>
  32. 36. <ul><li>Primary features: </li></ul><ul><li>Four features are required to be present of: </li></ul><ul><li>Rod-cone dystrophy </li></ul><ul><li>Polydactyly </li></ul><ul><li>Obesity </li></ul><ul><li>Learning disabilities </li></ul><ul><li>Hypogonadism in males </li></ul><ul><li>Renal anomalies </li></ul>
  33. 37. <ul><li>Three primary plus two secondary features are required of: </li></ul><ul><li>Secondary features </li></ul><ul><li>Speech disorder/delay </li></ul><ul><li>Strabismus /cataracts/astigmatism </li></ul><ul><li>Brachydactyly/syndactyly </li></ul><ul><li>Developmental delay </li></ul><ul><li>Polyuria/polydipsia (nephrogenic diabetes insipidus) </li></ul><ul><li>Ataxia/poor coordination/imbalance </li></ul><ul><li>Mild spasticity (especially lower limbs) </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Dental crowding/ hypodontia/small roots/ high arched palate </li></ul><ul><li>Left ventricular hypertrophy/congenital heart disease </li></ul><ul><li>Hepatic fibrosis </li></ul><ul><li>  </li></ul>
  34. 38. <ul><li>HYPOGONADISM IN OUR CASE </li></ul><ul><li>? </li></ul>
  35. 39. <ul><li>---probably due to primary gonadal </li></ul><ul><li>failure ,secondary to BBS per se </li></ul>
  36. 40. Case reports <ul><li>The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism. </li></ul><ul><li>Mozaffarian G , Nakhjavani MK , Farrahi A . </li></ul><ul><li>Abstract </li></ul><ul><li>The pathogenesis of hypogonadism and hypogenitalism was investigated in a male patient with the complete form of the Laurence-Moon-Bardet-Biedl syndrome. Synthetic gonadotropin-releasing hormone induced an increase in serum luteinizing hormone levels from 16.5 mIU/ml to 19.3 mIU/ml and in follicle-stimulating hormone levels from 18.5 mIU/ml to 25.9 mIU/ml. Serum testosterone levels were normal and did not rise after stimulation with human chorionic gonadotropin. The administration of thyrotropin-releasing hormone resulted in an increase in serum thyrotropin levels from 9.0 microU/ml to 12.0 microU/ml. Serum testoterone/estradiol-binding globulin, adrenocorticotropic hormone, and T3 resin uptake were normal. Serum cortisol showed a normal diurnal variation. The sex chromatin test was negative and the karyotupe revealed a 46,XY chromosome pattern. On biopsy, the left testis lacked germinal cells and the right testis showed spermatogenic arrest. Signs of hypogonadism and hypogenitalism persisted after 11 months of testosterone treatment. In this patient the target-organ unresponsiveness resulted in hypogenitalism and hypogonadism. </li></ul>
  37. 41. <ul><li>Empty sellae, impaired testosterone secretion, and defective hypothalamic-pituitary growth and gonadal axes in children with Bardet-Biedl syndrome. </li></ul><ul><li>Soliman AT , Rajab A , AlSalmi I , Asfour MG . </li></ul><ul><li>Source </li></ul><ul><li>Department of Pediatrics, Royal Hospital, Muscat, Oman. </li></ul><ul><li>Abstract </li></ul><ul><li>We evaluated growth parameters and hypothalamic-pituitary-gonadal and growth functions in five children with Bardet-Biedl syndrome (BBS). Three of the five children had stature below the fifth percentile for age. Their growth hormone (GH) response to provocation was defective, and computed tomographic (CT) scanning revealed empty sellae in all of them. All the children were obese (body mass index [BMI] > 95th percentile for age). Three had hypercholesterolemia. Their basal serum testosterone concentration and testosterone response to 3-day human chorionic gonadotropin (HCG) stimulation were significantly lower than the levels in 12 age-matched obese normal children. Testosterone secretion failed to respond to HCG therapy for 4 weeks. Both basal gonadotropin levels (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and gonadotropin responses to LH-releasing hormone (LHRH) stimulation were normal and did not differ among the two study groups . It appears that primary hypogonadism is a cardinal feature of BBS, and it may be accompanied by hypothalamic and pituitary abnormalities. </li></ul>
  38. 42. DISCUSSION <ul><li>Nomenclature : JZ Lawrence </li></ul><ul><li>RC Moon </li></ul><ul><li>Bardet LMBBS </li></ul><ul><li>Arthur Biedl </li></ul><ul><li>Cases reported by Lawrence and Moon --prog. spastic paraparesis and no polydactyly, obesity </li></ul><ul><li>Hence the term BARDET BIEDL SYNDROME </li></ul>
  39. 43. <ul><li>prevalence ---- 1 in 1,00,000 </li></ul><ul><li>Mode of inheritance – 1) Autosomal recessive </li></ul><ul><li>2) Multi allelic inheritance </li></ul><ul><li>--- individuals were homozygous /compound heterozygous for mutation at one locus but requires presence of a third heterozygous mutation to manifest phenotype </li></ul>
  40. 44. PATHOGENESIS OF BBS <ul><li>BBS genes (14) </li></ul><ul><li>BBS protein(basal body and cilia of cells) </li></ul><ul><li>Assembled to form “BBSome” </li></ul><ul><li>Transports intracellular vesicles to base of cilia </li></ul><ul><li>plays vital role in ciliary function </li></ul>
  41. 45. CILIOPATHIES <ul><li>Bardet –Biedl syndrome </li></ul><ul><li>primary ciliary dyskinesia </li></ul><ul><li>PCKD/Nephronophthisis </li></ul><ul><li>Alstrom syndrome </li></ul><ul><li>Meckel –gruber syndrome </li></ul>
  42. 46. EVALUATION AFTER DIAGNOSIS <ul><li>Ophthalmic assessment : visual acuity,field,refractory errors and fundus </li></ul><ul><li>BMI </li></ul><ul><li>Blood pressure </li></ul><ul><li>pelvic examination and USG </li></ul><ul><li>Renal function tests and Renal USG </li></ul><ul><li>Urine analysis –to R/O nephrogenic DI </li></ul><ul><li>Cardiac evalution-ECG,Chest X-ray,ECHO </li></ul><ul><li>Developmental assessment </li></ul>
  43. 47. <ul><li>GTT </li></ul><ul><li>Lipid profile </li></ul><ul><li>Liver function tests </li></ul><ul><li>Thyroid function tests </li></ul><ul><li>otoacoustic emissions/audiometry </li></ul><ul><li>dental examination </li></ul><ul><li>neurological assessment </li></ul>
  44. 48. MOLECULAR DIAGNOSIS <ul><li>14 genes – mapped till now </li></ul><ul><li>mutations – 1) sequence analysis </li></ul><ul><li>2) targeted mutation analysis </li></ul><ul><li>3) deletion/duplication analysis </li></ul><ul><li>Implications </li></ul><ul><li>probands carriers pre-natal diagnosis </li></ul>
  45. 49. TREATMENT MODALITIES <ul><li>Obesity – dietary mx, exercise, drug therapy for </li></ul><ul><li>dyslipidemias </li></ul><ul><li>Cognitive dysfunction,speech disorders – speech therapy </li></ul><ul><li>visual disturbances- low vision aids </li></ul><ul><li>ESRD- renal transplantation </li></ul><ul><li>In puberty – Hormonal assays and replacement therapy </li></ul><ul><li>Poly dactyly – removal of accessory digits </li></ul><ul><li>cardiac abnormalities, diabetes – guidelines as that of general population. </li></ul>
  46. 50. FOLLOW UP <ul><li>6 monthly : </li></ul><ul><li>urine analysis </li></ul><ul><li>blood urea ,creatinine </li></ul><ul><li>blood sugar </li></ul><ul><li>annual : </li></ul><ul><li>ophthal evaluation </li></ul><ul><li>lipid profile,TFT,LFT </li></ul><ul><li>renal USG` </li></ul>
  47. 51. <ul><li>PRIMARY ESS </li></ul><ul><li>SECONDARY ESS </li></ul><ul><li>there is a hole in membrane covering pituitary gland,sub arachnoid space herniates and compresses pituitary </li></ul><ul><li>Incidental finding </li></ul><ul><li>Hormones : N/mild </li></ul><ul><li>hyperprolactinemia </li></ul><ul><li>no specific treatment </li></ul><ul><li>pit. Gland is damaged by tumour ,radiation or </li></ul><ul><li>surgery </li></ul><ul><li>Pseudo tumour cerebri can cause ESS </li></ul><ul><li>Hormones : deficient </li></ul><ul><li>Requires replacement </li></ul>EMPTY SELLA SYNDROME
  48. 52. THANK U

×