174 / 492
S13: DSD
Moderators: Alexander Springer (Austria), Linda Baker (USA)
ESPU Meeting on Friday 16, October 2015, 09:00 - 09:46
09:00 - 09:05
S13-1
(LO)
★
FAMILY HISTORY OF GENITAL MALFORMATION IS UNDER-ESTIMATED IN
CHILDREN WITH ISOLATED HYPOSPADIAS: A CLINICAL REPORT OF 105
FAMILIES.
Nicolas KALFA
1
, Pascal PHILIBERT
1
, Sylvie BROUSSOUS
1
, Amandine COFFY
2
, Françoise AUDRAN
1
, Nadège FAUCONNET-
SERVANT
1
, Laura GASPARI
1
, Hélène LEHORS
3
, Myriam HADDAD
3
, Jean Michel GUYS
3
, Rachel REYNAUD
4
, Pierre
ALESSANDRINI
3
, Thierry MERROT
3
, Kathy WAGNER
5
, Jean BRÉAUD
6
, Jean Yves KURZENNE
6
, Florence BASTIANI
6
, Jean
Stéphane VALLA
6
, Gérard MORISSON LACOMBE
3
, Eric DOBREMEZ
7
, Christophe LOPEZ
1
, Jean-Pierre DAURES
2
, Françoise
PARIS
1
and Charles SULTAN
1
1) Hôpital lapeyronie-Arnaud de Villeneuve, CHU Montpellier, Service de Chirurgie et Urologie Pédiatrique et Unité
d'Endocrinologie Pédiatrqiue, Montpellier, FRANCE - 2) Université Montpellier, Institut Universitaire de recherche
clinique, Montpellier, FRANCE - 3) APHM, Service de Chirurgie et Urologie Pédiatrique, Marseille, FRANCE - 4) APHM,
Endocrinologie Pédiatrique, Marseille, FRANCE - 5) Hopital Lenval, Endocrinologie Pédiatrique, Nice, FRANCE - 6) Hopital
Lenval, Chirurgie et Urologie Pédiatrique, Nice, FRANCE - 7) CHU Bordeaux, Service de Chirurgie et Urologie Pédiatrique,
Bordeaux, FRANCE
PURPOSE
Severe forms of 46,XY DSD with uncertain sex may have a family history (FH) in approximately 15 to 20% of cases. On
the other side of the DSD spectrum, data regarding isolated hypospadias is sparse and a FH of genital malformation is
thought to be less frequent. The aims of the study were 1-to determine the frequency of genital abnormalities in families
of isolated hypospadiac boys, 2-to determine whether there is a particular phenotype and 3-to evaluate the prevalence
of genetic defects in familial cases.
MATERIAL AND METHODS
Prospective inclusion of hypospadiac boys screened for FH with a standardized questionnaire. Extensive clinical
description, family tree, DNA sampling and sequencing of androgen receptor, 5 alpha-reductase and SF1 genes were
performed.
RESULTS
Out of a series of 395 boys with hypospadias, 105 had a FH of genital malformation (hypospadias n=88, cryptorchidism:
n=17). FH was thus more frequent than expected (26.6%). The familial cases were mainly unique (80%, multiple in
20%). Familial hypospadias were more frequently related to the paternal side (53.4% of cases) including the father
himself (29.5%), the paternal uncles and/or cousins. Prematurity, use of ART, other congenital abnormalities and
postnatal growth retardation were not more frequent in familial hypospadias. The severity of phenotype and ethnicity
were not significantly different either. Intrauterine growth retardation tended to be less frequent in familial forms
(p=0.07). Mutations of AR and SF1 were more frequent in familial hypospadias (n=5, 5.68% vs 1.60%, p=0.046). (for
AR: P392S, Q798E, A475V, P392S; for SF1: D275N)
CONCLUSIONS
FH is more frequent in hypospadiac boys than previously reported. It involves more than a quarter of cases. Even
isolated and minor hypospadias justify a full interrogation on FH. Detecting these familial forms may justify an etiologic
work-up to find out the causative mutation, to improve the follow-up of these patients and to help the family counseling.