1. Disorder of the sex development Rickets
A. Luczay

2. Sex development GENETIC X X X Y (chromosal) GONADAL ovarium testis
GENITAL
INTERNAL uterus prostate
EXTERNAL female male
SEX ASSIGNMENT girl boy
PSYCHOSOCIAL female male

3. DIFFERENTIATION OF THE GONADS
PRIMORDIAL GERM CELS
ADRENAL MEDULLA
ADRENAL CORTEX
WOLFFIAN DUCT
MÜLLERIAN DUCT
MEDULLA
CORTEX
BIPOTENTIAL GONAD
46 XX
46 XY
DEVELOPING TESTIS
DEVELOPING OVARY
TUBULUBI SEMINIFERIS
WOLFFIAN DEGENERATION
CONDUCTING DUCT
PRIMARY FOLLICLES
SPERMATO-
GONIUMS
MÜLLERIAN DUCT REGRESSION
FALLOPIAN TUBE

4. GENITAL DIFFERENTIATION
INDIFFERENT STAGE
GONAD
MESONEPHROS
MÜLLERIAN DUCT
WOLFFIAN DUCT
UROGENITAL FOLD
INDIFFERENT STAGE
LABIOSCROTAL
SWELLING
MALE
FEMALE
GLANS
UROGENI-
TAL FOLD
FUSIONED UROGENITAL FOLD
URETH-RAL SLIT
EPIDIDYMIS
OVARY
TESTIS
FALLO-PIAN
TUBE
VAS DEFERENS
ANUS
GLANS PENIS
URETHRAL MEATUS
UTERUS
SEMINAL VESICLE
CLITORIS
PROSTATE
VAGINAL ORIFICE
VAGINA
RAPHE
FEMALE
MALE

5. DISORDERS OF THE EXTERNAL GENITALIA
SINECKER
PRADER

6. CLINICAL ASSESSMENTOF INFANTS WITH AMBIGUOUS GENITALIA
GONADS
PALPABLE
NON-PALPABLE
NORMAL
NORMAL
INCREASED
KARYOTYPE
SERUM Te HIGH LOW

7. Classification

8. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovotesticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

9. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovoteticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

10. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovoteticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

13. Turner syndrome 1/2500 live female birth Hand-food edema in infancy
Pterygium colli (neck webbing), Low posterior hairline, Broad chest, short stature
Cardiac, renal malformations
Karyotype: 45,X

14. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovotesticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

18. Klinefelter syndrome 1/500-1000 live male birth
Small testis, high stature, learning difficulties, gynecomastia in puberty
At pubert testicular size increases (~10 ml)
Midpuberty: low androgen level
Karyotype: 47,XXY

19. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovotesticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

21. Complet gonadal dysgenesis Swyer syndrome
Bilateral streak gonads
Apparently normal female external genitalia
High risk of gonadoblastoma, germinoma
Karyotype: 46,XY

22. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovotesticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

24. Parcial gonadal dysgenesis
Ambigous genitalia (Leydig cell mass)
Partial rest of Müllerian duct
Karyotype: 46,XY
High risk of gonadoblastoma

25. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovoteticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

27. Steroid Hormone Biosynthesis
dehidroepiandrosterone HO O
17a-OH-progesterone
cholesterol
ALDOSTERONE
Pregnenolone
Progesterone
11-Dezoxycortisol
Corticosterone
CORTIZOL
17a-OH-pregnenolone C
CH3
DOC
CH2OH
OCH OH 17
ANDROSTENEDIONE

28. 17- hydroxilase defect Rare form of CAH
Both testosterone and estrogen synthesis is decreased
Hypertension, hypokalemia

29. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovoteticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

31. Complete androgen insensitivity
X q11-12 – AR gene
Female external genitalia, good breast development, hairless
Low risk of gonadoblstoma (2-5%)

32. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovoteticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

34. Parcial androgen insensitiviy
X q11-12
The seerity of undervirilisation depend on the receptor sensitivity.
High risk of gonadoblastoma

35. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen over production
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defektus
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovoteticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

37. Steroid Hormone Biosynthesis
dehidroepiandrosterone HO O
17a-OH-progesterone
cholesterol
ALDOSTERONE
Pregnenolone
Progesterone
11-Dezoxycortisol
Corticosterone
CORTIZOL
17a-OH-pregnenolone C
CH3
DOC
CH2OH
OCH OH 17
ANDROSTENEDIONE
P450c21

38. Cngenital adrenal hyperplasia (21-OHD)
1/15000 live birth
CYP21 gene mutation
2/3 salt wasting form

39. SEX CHROMOSOME DSD
DSD KARYOTYPE : 46,XY
DSD KARYOTYPE: 46,XX
Disorder of testicular development
Disorder of ovarian development
45,X Turner syndrome
1. Complet Gonadal Dysgenesis
(Swyer syndroma)
1. Ovotesticular DSD
2. Partial Gonadal Dysgenesis
2. testis SRY+,
SOX9 duplication
3. Testicular regression
3. gonadal dysgenesis
4. Ovotesticular DSD
47, XXY Klinefelter syndrome
Defect in androgen biosynthesis or in androgen action
Androgen overproduction
1. defect in biosynthesis (17hydroxilase defect,
17 HSD, 5reductase defect, Star mutation)
1. fetal origin: 21-OH def./11OH def.
2. fetoplacental origin aromatase defect
3. maternal origin:
luteoma, exogén
2. defect in action
(CAIS, PAIS)
45X/46,XY Mixed gonadal dysgenesis
(ovoteticular DSD)
46,XX/46,XY Chimeric ovotesticular DSD
3. LH receptor mutation
(Leydig-hypoplasia, aplasia)
4. Persistent Müllerian duct syndrome

41. Treatment

42. TS

44. KS

45. 17  -OH

46. CGD

47. CAIS

48. 21 OH

49. PGD

50. PAIS

52. Rickets

53. Definition
Decrease in the enchondral calcification of the growth plate.
Growth plate deformities
Decreased growth rate
Skeletal deformities
In adults: osteomalacia

54. Clinical signs Decreased growth rate Big fontanelle, craniotabes
Swelling around growth plate:
Rachitic bracelet

55. Bowleg (genu varum) windswept
(genu varum + genu valgum)

56. Rachitic rosary Harrison’s sulcus

57. Radiographic findings
Loss of demarcation
Growth plate widens
Irregular outlines
Metaphysis cuped, flared

58. Classification Calciopenic Vitamin D-deficient
Vitamin D 1- hydrohylase deficiency
Hereditary
1,25 (OH)2 D resistant
Phospopenic
X-linked hypophosphatemic
AD hypophosphatemic
Hereditary hypophosphatemic rickets with hypercalciuria
Renal tubular disorder – Fanconi sy.

59. Vitamin D- deficient rickets
Inadequate vitamin D intake or formation in the skin (UV B dependent)
3-18 moths of age
Breatsfeeding high risk
IU/ day

60. Stages of vitamin D-deficient rickets
25(OH)D  

Calcium
Low N
PTH
Starts to rise  
Phosphorus N
low
ALP

61. Treatment Prevention 400-600 IU/ day
Vitamin D IU/ day – 6-8 weeks
( IU inramuscular)
Ca supplementation: mg/ day
Prevention
IU/ day

62. Vitamin D 1- hyroxylase deficiency Vitamin D dependent rickets type I
renal 1 - hydroxylase is inactive
During the first 2 years of life
Treatment
0,25-2,0 ug/day calcitriol + calcium

63. Hereditary 1,25 (OH)2- resistant rickets Vitamin D dependent rickets typeII
vitamin D receptor mutation- ressitance to vitamin D
Treatment
very high dose of calcitriol

64. X-linked hypophosphatemic rickets
PHEx (phosphate-regulating gene with homologie to endopeptidases) X kr.
Renal phosphate wasting
hypophospataemia
inapproprate 1,25 (OH)2 D
Treatment
Elemental phosphorus + calcitriol

65. AD hypophosphatemic rickets
Rare disorder
FGF23 (fibroblast growth factor family)
Presentation: childhood, adulthood

66. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)
Similar to XLH
BUT: appropriate 1,25 (OH)2 Vit. D
hypercalciuria – kidney stones
Treatment
Phosphorus supplementation

67. Renal tubular disosrders- Fanconi syndrome
Defects in the reabsorption of ion
(Mg, P, Ca, Na, K, HCO3-),
glucose, amino acids
Causes: cystinosis, tyrosinaemia, galactosemia, Lowe syndrome
Treatment
phosphorus, calcitriol

68. Biochemical finding in different forms of rickets
Serum
Urine Ca P
PTH
ALP
25(OH)D
1,25(OH)
TRP
AAS
Vit.D def N
N/L
H/N H L
L/N/H -
1 def
Vit.D res. HH
Hypophos.
~+ hypercalciuria
Fanconi +