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Erin Moseley
Pseudohermaphroditism - Male (MPH)


Incomplete masculinization of the external genitalia in
a male (46XY) karyotype.
If the testes form only partially and the production of
androgen and Mullerian inhibitor is incomplete,
there will be only partial masculinization of the
external genitalia as well as incomplete inhibition
of the development of the vagina, uterus, and
Fallopian tubes.
Pseudohermaphroditism - Male


A rare autosomal recessive disorder of genetic (XY) males.
Ambiguous external genitalia appearing in adolescence.
- Characterized by a clitoris-like phallus, bifid scrotum,
and urogenital sinus with a blind vaginal pouch.
-Testes are undescended pre-pubescently, are
usually located in the abdomen, inguinal canals, or
scrotal folds.

Causes initial misdetermination of sex at birth.
The gonads are testicles which are usually retained. The
tubular components are basically female. The external
genitalia are mainly of the female type with an enlarged
clitoris, or may be vestigial penile development.
Pseudohermaphroditism - Female
A virilized female
Masculinization of the external genitalia by an
abnormal source of androgen
Internal genitalia are normal, such as the vagina
and uterus.

The gonads are ovaries and the
accessory sex organs are predominantly
male.
 Male chromosomes -- X,Y
 High testosterone and luteinizing hormone level in blood
 Low or absent sperm count
 Testicular biopsy shows no mature sperm despite normal precursors
 Decreased or absent vas deferens (the tubes through which sperm exit the
testes)
 Partial development of female gonads/sex organs
 Decreased ability to bind androgen in cell culture tests
 Mutations in the androgen receptor gene
 Family history of affected males who share a common, unaffected female
relative consistent with X-linked recessive inheritance
Abnormal male genitalia, including undescended
testes; scrotum that is small, with a line down the
middle (bifid) or incompletely closed; small penis and
hypospadias (penis tethered to underlying skin)
Breast development in males at time of puberty
Lack of fertility
 Decreased body hair and beard with normal pubic
and armpit hair
This disease is one of a spectrum of diseases that are due to
loss of normal response to the male sex hormones, called
androgens (of which testosterone is the best known). In this
genetic disease, the affected gene codes for the androgen
"receptor." This is the key protein inside cells that receives the
androgen hormone and instructs the cell how to respond to
androgen hormones.
Location- Chromosome X
Address- Xq12
CGAGATCCCGGGGAGCCAGCTTGCTGGGAGAGCGGGACGGTCCGGAGCAAGCC
CAGAGGCAGAGGAGGCGACAGAGGGAAAAAGGGCCGAGCTAGCCGCTCCAGTG
CTGTACAGGAGCCGAAGGGACGCACCACGCCAGCCCCAGCCCGGCTCCAGCGA
CAGCCAACGCCTCTTGCAGCGCGGCGGCTTCGAAGCCGCCGCCCGGAGCTGCC
CTTTCCTCTTCGGTGAAGTTTTTAAAAGCTGCTAAAGACTCGGAGGAAGCAAG
GAAAGTGCCTGGTAGGACTGACGGCTGCCTTTGTCCTCCTCCTCTCCACCCCG
CCTCCCCCCACCCTGCCTTCCCCCCCTCCCCCGTCTTCTCTCCCGCAGCTGCC
TCAGTCGGCTACTCTCAGCCAACCCCCCTCACCACCCTTCTCCCCACCCGCCC
CCCCGCCCCCGTCGGCCCAGCGCTGCCAGCCCGAGTTTGCAGAGAGGTAACTC
CCTTTGGCTGGAGCGGGCGAGCTAGCTGCACATTGCAAAGAAGGCTCTTAGGA
GCCAGGCGACTGGGGAGCGGCTTCAGCACTGCAGCCACGACCCGCCTGGTTAG
GCTGCACGCGGAGAGAACCCTCTGTTTTCCCCCACTCTCTCTCCACCTCCTCC
TGCCTTCCCCACCCCGAGTGCGGAGCCAGAGATCAAAAGATGAAAAGGCAGTC
AGGTCTTCAGTAGCCAAAAAACAAAACAAACAAAAACAAAAAAGCCGAAATAA
AAGAAAA
Mutation type
Nucleotide substitutions (missense / nonsense)
Total number of mutations
195
Nucleotide substitutions (splicing)
9
Nucleotide substitutions (regulatory)
2
Small deletions
14
Small insertions
7
Small indels
0
Gross deletions
15
Gross insertions & duplications
1
Complex rearrangements (including inversions)
0
Repeat variations
4
TOTAL
247
Examples of Insertion Mutations
Accession
Number
Nucleotide
CI962560
Codon
Insertion
Phenotype
Reference
52
C
Androgen insensitivity syndrome
1
CI994028
542
60
A
Androgen insensitivity syndrome
2
CI993488
617
85
A
Androgen insensitivity syndrome
3
CI920926
966
202
ATCC
Androgen insensitivity syndrome
4
215
G
Androgen insensitivity syndrome
5
553
ACTATTAC
Androgen insensitivity syndrome
6
848
A
Androgen insensitivity syndrome
7
CI941827
CI962561
CI000491
2011
SEQUENCE 919 AA; 98988 MW; 93B096927740B6FF CRC64;
MEVQLGLGRV YPRPPSKTYR GAFQNLFQSV REVIQNPGPR HPEAASAAPP
GASLLLLQQQ QQQQQQQQQQ QQQQQQQQET SPRQQQQQQG
EDGSPQAHRR GPTGYLVLDE EQQPSQPQSA LECHPERGCV PEPGAAVAAS
KGLPQQLPAP PDEDDSAAPS TLSLLGPTFP GLSSCSADLK DILSEASTMQ
LLQQQQQEAV SEGSSSGRAR EASGAPTSSK DNYLGGTSTI SDNAKELCKA
VSVSMGLGVE ALEHLSPGEQ LRGDCMYAPL LGVPPAVRPT PCAPLAECKG
SLLDDSAGKS TEDTAEYSPF KGGYTKGLEG ESLGCSGSAA AGSSGTLELP
STLSLYKSGA LDEAAAYQSR DYYNFPLALA GPPPPPPPPH PHARIKLENP
LDYGSAWAAA AAQCRYGDLA SLHGAGAAGP GSGSPSAAAS SSWHTLFTAE
EGQLYGPCGG GGGGGGGGGG GGGGGGGGGG GGEAGAVAPY
GYTRPPQGLA GQESDFTAPD VWYPGGMVSR VPYPSPTCVK SEMGPWMDSY
SGPYGDMRLE TARDHVLPID YYFPPQKTCL ICGDEASGCH YGALTCGSCK
VFFKRAAEGK QKYLCASRND CTIDKFRRKN CPSCRLRKCY EAGMTLGARK
LKKLGNLKLQ EEGEASSTTS PTEETTQKLT VSHIEGYECQ PIFLNVLEAI
EPGVVCAGHD NNQPDSFAAL LSSLNELGER QLVHVVKWAK ALPGFRNLHV
DDQMAVIQYS WMGLMVFAMG WRSFTNVNSR MLYFAPDLVF NEYRMHKSRM
YSQCVRMRHL SQEFGWLQIT PQEFLCMKAL LLFSIIPVDG LKNQKFFDEL
RMNYIKELDR IIACKRKNPT SCSRRFYQLT KLLDSVQPIA RELHQFTFDL
LIKSHMVSVD FPEMMAEIIS VQVPKILSGK VKPIYFHTQ
ANDROGEN
RECEPTOR
The effect of testosterone replacement on the psychological well-being of 20
women with CAIS. Women randomly received a skin patch containing active
testosterone or a dummy placebo. The testosterone was administered as an
adhesive patch applied daily. A new patch system was used in this study - one
that is usually used in men with testosterone deficiency. After 8 weeks the
treatment will be swapped so that all women with receive testosterone at some
time. The entire study will take place over the course of 16 weeks. All
volunteers will continue their usual estrogen replacement therapy during the
trial.
Personality
traits and platelet monoamine oxidase (MAO) activity were
studied in 22 women, 17-34 years old, with prenatal virilization due to
congenital adrenal hyperplasia (CAH) (21-hydroxylase deficiency) and 22
healthy controls. The CAH group differed significantly on two of the
eight scales of the Karolinska Scales of Personality (KSP), which have
earlier shown significant gender differences. Both differences were in
the masculine direction, with a high, male level, score for Detachment
and a lower score for Indirect Aggression. The Detachment scale reflects
distance in social relations, and has earlier been shown to be strongly
gender differentiating. There was no significant difference in platelet
MAO activity between the CAH group and the controls. Although an
influence of psychosocial factors cannot be excluded, the results
suggest a possible association between prenatal androgen exposure and
the high Detachment score for the CAH group. Gender differences in
empathy, affiliation motivation, intimacy and maternal behavior may be
relevant parallels
Nine female adolescents with female pseudohermaphroditism
resulting from virilizing congenital adrenocortical hyperplasia (CAH) were
studied in terms of gender identity, sex-role behavior, psychological
adjustment, and psychosexual development. A group of adolescents with
chronic illness was used as a control. The Draw-A-Person, the Bem SexRole Inventory, Rorschach, TAT, and a questionnaire reviewing peer and
romantic activities were administered to both groups. The two groups
were comparable on measures of general personality greater bodily
concerns. Sex-role identity for both groups was near the adolescent girl
norms for both Femininity and Masculinity, with virilized CAH girls
showing slightly higher Androgyny scores. Significant differences were
found on gender identity as measured by greater differentiation of the
drawn male figure as well as a trend toward drawing the male figure
first. The CAH females also showed consistent patterns of psychosocial
delay in dating and sexual relations as compared to the control group.
Gender identity in this group appears to be mediated by body image. The
resulting ambivalence may be evidence of feelings of incompetence,
leading to resistance to social interactions and goals involving intimacy
and nurturance.
Prenatal Diagnosis & Treatment
Prenatal diagnosis done by molecular genetic analysis
using DNA extracted from chorionic villus cells in the
amniotic fluid.
Analysis of fetal P450c21B genes can determine 21
OH deficiency. ( Congenital Adrenal Hyperplasia)
Causitive mutations can be identified on 95% of
Chromosomes using Southern blot analysis and
selective amplification of the CYP21B gene by
polymerase chain reaction.
Prenatal Diagnosis &Treatment
Prenatal prediction of CAH deficiency allows doctors to
prevent virilization of affected female fetus
Treatment begins in the 5th week of gestation.
Mothers are given 20-25 kg of dexamethasone per day
until fetus is delivered.
Three fourths of treated cases respond successfully with
female born with either normal genitalia or only mildly
virilized genetalia.
Post Natal
Treatment
-Male gender identity and hormone replacement therapy
Some evidence suggests that DHT therapy administered prior
to puberty may increase penile size. DHT therapy is ineffective
once puberty starts, probably because it merely suppresses
and replaces the endogenous production of testosterone,
maintaining a normal total serum level.
Most males virilize adequately for normal sexual function
without replacement. The unaffected less active 5-ARD type 1
enzyme may provide adequate activity for this; or, even with
the lower level of receptor binding, the large amount of
testosterone produced at puberty may suffice for this
masculinization.
Post Natal Treatment
-Female gender identity and hormone replacement therapy
After gonadectomy, which should be performed prior to puberty
and usually is performed in the newborn period, start hormone
replacement therapy at an appropriate age.
Many endocrinologists use an arbitrary bone age of approximately
13 years; starting therapy too early causes premature epiphyseal
fusion.
Other endocrinologists start measuring luteinizing hormone (LH)
and follicle-stimulating hormone (FSH) when the individual is aged
approximately 10 years and begin therapy when the gonadotropins
begin to rise.
Either ethinyl estradiol or conjugated estrogens can be used
initially.
Progesterone usually is not added in the absence of a uterus.