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D u r i n g t h i s e l o n g a t i o n, the p h a l l u s p u l l s the u r e t h r a l f o l d s f o r w a r d s o t h a t) the y f o r m the l a t e r a l w a l l s o fr e hh r a l g r o o v T h i s g r o o v e e xt e n d s a l o n g the u tte. T h e e p i the l i a l l i n i n g o f the g r o o v e, w h i c h o r i g i n a t e s i n the e n d o d e r m, f o r ms the u r e t h r a l p l a t(F i g. D e v e l o p me n t o f e xt e r n a l g e n i t a l i a i n the ma l e a t 1 0 w e e k s. T h i s c a n a l d o e s n o t e xt e n d e (F B) t o the t i p o f the p h a l l u s. T h i s c o r d l a t e r o b t a i n s a l u me n, t h u s f o r mi n g the e x t e r n a l u r e t h r a l m e a(Fu g. T h e g e n i t a l s w e l l i n g s, k n o w n i n the ma l e a s the s c r o t a l s w e l l i n g s, a r i s e i n the i n g u i n a l r e g i o n. W i t h f u r the r d e v e l o p me n t the y mo v e c a u d a l l y, a n d e a c h s w e l l i n g the n ma k e s u p h a l f o f the s c r o t u m. In u t e r o p h o t o g r a p h o f the g e n i t a l i a o f a ma l e f e t u s a t 1 2 4 weeks. Note that the urethral folds are fusing and that the scrotal swellings are e n l a r g i n g t o me r g e i n the mi Bl. W h e n f u s i o n o f the u r e t h r a l f o l d s f a i l s e n t i r e l y, a w i d e s a g i t t a l s l i t i s f o u n d a l o n g the e n t i r e l e n g t h o f the p e n i s a n d the s c r o t u m. T h e t w o s c r o t a l s w e l l i n g s the n c l o s e l y r e s e mb l e the l a b i a ma j o r a. Reasons for the increase are not known, but one hypothesis suggests it could be a result of a r i s e i n e n v i r o n me n t a l e s t r o g e n s (e n d o c r i n e d i s r uC ho rp t;e s. In s t e a d o f d e v e l o p i n g a t the c r a n i a l ma r g i n o f the c l o a c a l me mb r a n e, the g e n i t a l t u b e r c l e s e e ms t o f o r m i n the r e g i o n o f the u r o r e c t a l s e p t u m. Al t h o u g h e p i s p a d i a s ma y o c c u r a s a n i s o l a t e d d e f e c t, i t i s mo s t o f t e n a s s o c i a t e d w i the xs t r o p h y o f the b l a d d e r. H y p o s p a d i a s s h o w i n g the v a r i o u s l o c a t i o n s o f a b n o r ma l 5 u r e t h r a l o r i f i c e s. T h e u r e t h r a i s o p e n o n the B v e n t r a l s u r f a c e o f the p e n iE p i s p a d i a s c o mb i n e d w i the xs t r o p h y o f the C. W h e n t h i s mi g r a t i o n d o e s n o t o c c u r, r u p t u r e o f the c l o a c a l me mb r a n e e xt e n d s c r a n i a l l y, c r e a t i n g e xs t r o p h y o f the b l a d d e r. M i c r o p e n i s c c u r s w h e n the r e i s i n s u f f i c i e n t a n d r o g e n s t i mu l a t i o n f o r g r o w t h o f o the e xt e r n a l g e n i t a l i a. M i c r o p e n i s i s u s u a l l y c a u s e d b y p r i ma r y h y p o g o n a d i s m o r h y p o t h a l a mi c o r p i t u i t a r y d y s f u n c t i o n. T h e g e n i t a l t u b e r c l e e l o n g a t e s o n l y s l i g h t l y a n d co ir tms i ts s e eF i g s. Al t h o u g h the v t st (F B) g e n i t a l t u b e r c l e d o e s n o t e l o n g a t e e xt e n s i v e l y i n the f e ma l e, i t i s l a r g e r t h a n i n the ma l e d u r i n g the e a r l y s t a g e s o f d e v e l o p me n t. In f a c t, u s i n g t u b e r c l e l e n g t h a s a c r i t e r i o n (a s mo n i t o r e d b y u l t r a s o u n d) h a s r e s u l t e d i n mi s t a k e s i n i d e n t i f i c a t i o n o f the s e xe s d u r i n g the t h i r d a n d f o u r t h mo n t h s o f g e s t a t i o n. P a t i e n t s a r e c h a r a c t e r i ze d b y i n f e r t i l i t y, g y n e c o ma s t i a, v a r y i n g d e g r e e s o f i mp a i r e d s e xu a l ma t u r a t i o n, a n d i n s o me c a s e s, u n d e r a n d r o g e n i za t i o n. In g o n a d a l d y s g e n e s i o c y t e s a r e a b s e n t a n d the o v a r i e s a p p e a r a s s t r e a k os g o n a d s. T hey have a 45,X karyotype and a short stature, high arched palate, webbed neck, shield-like chest, cardiac and r e n a l a n o ma l i e s, a n d i n v e r t e d n i p p l e s g(. In s o me c a s e s, the s e a b n o r ma l i t i e s r e s u l t i n i n d i v i d u a l s w i t h c h a r a c t e r i s t i c s o f b o t h s e xe s, k n o w n m a p h r o d i t. E xt e r n a l g e n i t a l i a a r e a mb i g u o u s o r p r e d o mi n a n t l y f e ma l e, a n d mo s t o f the s e i n d i v i d u a l s a r e r a i s e d a s f e ma l e s. In p s e u d o h e r m a p h r o d i,t eh e g e n o t y p i c s e x i s ma s k e d b y a p h e n o t y p i c ts a p p e a r a n c e t h a t c l o s e l y r e s e mb l e s the o the r s e x. W h e n the p s e u d o h e r ma p h r o d i t e h a s a t e s t i s, the p a t i e n t i s c a l l e d a ma l e p s e u d o h e r ma p h r o d i t e; w h e n a n o v a r y i s p r e s e n t, the p a t i e n t i s c a l l e d a f e ma l e p s e u d o h e r ma p h r o d i t.

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T h e f o u r c o mp o n e n t s 8 o B o f the d e f e c t: p u l mo n a r y s t e n o s i s, o v e r r i d i n g a o r t a, i n t e r v e n t r i c u l a r s e p t a l defect, and hypertrophy of the right ventricle. T h e p u l mo n a r y a r t e r y o r i g i n a t e s 9 f r o m a c o mmo n t r u n c A s the s e p t u m i n the t r u n c u s a n d c o n u s h a s f a i l e d (u). T h i s a b n o r ma l i t y i s a l w a y s a c c o mp a n i e d b y a n i n t e r v e n t r i c u l a r (septal defect. V a l v u l a r s t e n o so s the p u l mo n a r y a r t e r y o r a o r t a o c c u r s w h e n the s e mi l u n a r if v a l v e s a r e f u s e d f o r a v a r i a b l e d i s t a n c. T h e i n c i d e n c e o f the a b n o r ma l i t y i s s i mi l a r f o r b o t h r e g i o n s, b e i n g a p p r o xi ma t e l y 3 t o 4 / 1 0, 0 0 0 b i r t h s. In the c a s e o f a v a l v u l a r s t e n o s i s o f the p u l m o n a r y, a r the r r u n k o f the p u l mo n a r y th e t y a r t e r y i s n a r r o w o r e v e n a t Fegi. T h e d u c t u s a r t e r i o s u s, a l w a y s p a t e n t, i s the o n l y a c c e s s r o u t e t o the p u l mo n a r y c i r c u l a t i o n. T h e o n l y a c c e s s r o u t e t o the l u n g s i s b y way of a patent ductus arteriosus. W h e n f u s i o n o f the s e mi l u n a r a o r t i c v a l v e s i s ca o r t il e t e - v u l a r a t r e s i a o mp c v a l (F i g. T h e a b n o r ma l i t y i s u s u a l l y a c c o mp a n i e d b y a n o p e n d u c t u s arteriosus, which delivers blood into the aorta. E c t o p i a c o r d i s a r a r e a n o ma l y i n w h i c h the h e a r t l i e s o n the s u r f a c e o f the c h e s t. It i s c a u s e d b y f a i l u r e o f the e mb r y o t o c l o s e the v e n t r a l b o d y w a l l (s e e C h a p t e r 11). T h e c o r o n a r y a r t e r i e s a r e s u p p l i e d b y t h i s r e t r o f l u x. N o t e the s ma l l l e f t v e n t r i c l e a n d the l a r g e r i g h t ventricle. Form ation of the Conducting Sy ste m of the He art In i t i a l l y t h ea c e m a k e r o r the h e a r t l i e s i n the c a u d a l p a r t o f the l e f t c a r d i a c t u b. Once the sinus venosus is incorporated into the right atrium the s e c e l l s l i e i n the i r f i n a l p o s i t i o n a t the b a s e o f the i n t e r a t r i a l s e p t u m. Vascular De v e lopm e nt B l o o d v e s s e l d e v e l o p me n t o c c u r s b y t w o me c h a n i s ms u l(o g e n e s i s v asc: 1) n w h i c h v e s s e l s a r i s e b y c o a l e s c e a n e i o fb l a s t sa n d (2 a n g i o g e n e s i s nc g o;) w h e r e b y v e s s e l s s p r o u t f r o m e xi s t i n g v e s s e l s. T h e r e ma i n d e r o f the v a s c u l a r s y s t e m the n f o r ms b y a n g i o g e n e s i s. T h e e n t i r e s y s t e m i s p a t t e r n e d b y g u i d a n c e c u e s i n v o l v i n g c u l a r e n d o the l i a l g r o w t h f (Vc t Gr) a n d o the r v as a EoF growth factors. Arterial System Aortic Arche s W h e n p h a r y n g e a l a r c h e s f o r m d u r i n g the f o u r t h a n d f i f t h w e e k s o f d e v e l o p me n t, e a c h a r c h r e c e i v e s i t s o w n c r a n i a l n e r v e a n d i t s o w n C r ta p ye (s1 6 a h e r t r. T h e a o r t i c a r c h e s a r e e mb e d d e d (i ee a) i n me s e n c h y me o f the p h a r y n g e a l a r c h e s a n d t e r mi n a t e i n the r i g h t a n d l e f t d o r s a l a o r t a.

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