Gonadal Agenesis in a 46, XY Female with Multiple Malformations and Positive Testing for the Sex-Determining Region of the Y Chromosome

Abstract

A full-term 46, XY female newborn presented with respiratory failure due to a right-sided diaphragmatic hernia. During surgical repair, exploration revealed isolated dextrocardia and hypoplasia of the right lung. Neither gonads nor wolffian or müllerian structures could be palpated. Cardiac catheterization demonstrated defects of the ventricular septum, hypoplasia of the right pulmonary artery, persistence of the left vena cava superior and a patent ductus arteriosus. Anthropometric data were normal at birth, but fell below the 3rd percentile during follow-up. Body proportions displayed a predominance of the upper compared to the lower segment. Endocrine studies indicated no defect of steroid biosynthesis and no functional gonadal tissue. Using genetic analyses of various loci within the testis-determining region of the Y chromosome, a mutation could not be detected. The patient died from pneumonia at the age of 19 months. Postmortem examination confirmed the diagnosis of gonadal agenesis.

Vitamin A deficiency in an infant with PAGOD syndrome

“…Eleven cases (9 male and 2 female) have been reported to date (Table II) [Meacham et al, 1991;Sorgo et al, 1991;Maaswinkel-Mooij and Stokvis-Brantsma, 1992;Kennerknecht et al, 1993;Oyer et al, 1994;ManouvrierHanu et al, 2000;Macayran et al, 2002;Kim et al, 2007]. All have been isolated/sporadic except for a single report of this phenotype in a set of siblings suggesting the possibility of an autosomal recessive condition [Kennerknecht et al, 1993].…”

“…Maaswinkel-Mooij and Stokvis-Brantsma [1992], Meacham et al [1991], and Sorgo et al [1991] independently reported four patients with a constellation of specific genital, pulmonary and cardiac malformations, normal karyotype, and negative family history of similar defects, consanguinity or known exposure to teratogens. The patients were term infants of normal size with hypoplastic right lungs, abnormalities of the ipsilateral diaphragm, anomalous pulmonary venous return, left ventricular hypoplasia, and shift of the heart to the right hemithorax (dextroposition).…”

A case of PAGOD syndrome with hypoplastic left heart syndrome

“…Several additional reports followed, with their unique features of combined anomalies: pulmonary artery and lung hypoplasia, diaphragm defects, omphalocele, sex reversal or ambiguous genitalia, and complex cardiac defects [1][2][3][4]. Kennerknecht et al proposed the acronym PAGOD ( pulmo, and pulmonary artery hypoplasia, agonadism, omphalocele/diaphragm defect, dextrocardia) to refer to this extremely rare syndrome [2].…”

Clinical expression and SRY gene analysis in XY subjects lacking gonadal tissue

“…In the majority of patients with primary agonadism, both male and female internal genitalia generally are absent, indicating an adequate function of the mu È llerian-inhibiting substance (MIS) before testicular degeneration [Edman et al, 1977;Penney and Betz, 1977;De Marchi et al, 1981;Marcantonio et al, 1994]. Subjects with 46,XY agonadism frequently have several physical malformations that include craniofacial [Marcantonio et al, 1994], cardiac [Edman et al, 1977;Sorgo et al, 1991;Kennerknecht et al, 1993], limb [Marcantonio et al, 1994], and renal defects [Kennerknecht et al, 1995] as well as mental retardation [Maciel-Guerra et al, 1991;Kennerknecht et al, 1995]. Josso and Briard [1980] described a family with two 46,XY agonadic siblings; one of them had female external genitalia, and the other was a phenotypic male with micropenis.…”

“…In several previous reports, the SRY gene was analyzed in subjects with agonadia [Sorgo et al, 1991;Pivnick et al, 1992;Lobaccaro et al, 1993;Marcantonio et al, 1994;Mendonca et al, 1994;Kennerknecht et al, 1995]. No mutations were found, but in most of these patients only the HMG box coding region of the SRY gene was studied.…”