IllnessHypogonadism, male hypergonadotropic; differential diagnosis

NGS +

[Sanger]

Hypogonadism refers to a disorder of the hypothalamic/pituitary/testicular axis leading to androgen deficiency as well as infertility. Pre-pubertal androgen deficiency may manifest as micropenis and testicular maldescensus and later be associated with delayed puberty and eunuchoid proportions. After puberty, nonspecific features often appear, varying according to the rate and extent of testosterone decline. In many infertile men, potency may be relatively preserved, because the germinal epithelium is more susceptible to both congenital and acquired defects. Most commonly, hypogonadism is due to congenital or acquired defects of the testes (primary testicular insufficiency), and gonadotropin levels (LH, FSH) are elevated. Klinefelter syndrome (47XXY) is the most frequent cause with about 1/700 male newborns. The rare monogenic defects follow all classical inheritance patterns. The diagnostic yield by molecular genetics is unknown.

Reference: https://www.mja.com.au/journal/2016/205/4/endocrine-society-australia-position-statement-male-hypogonadism-part-1

• Allelic: 46XX sex reversal 4 (NR5A1)
• Allelic: 46XY sex reversal 3 (NR5A1)
• Allelic: Adrenocortical insufficiency (NR5A1)
• Allelic: Brachydactyly, type A1, D (BMPR1B)
• Allelic: Brachydactyly, type A2 (BMPR1B)
• Allelic: Cardiomyopathy, dilated, 1A (LMNA)
• Allelic: Charcot-Marie-Tooth disease, type 2B1 (LMNA)
• Allelic: Emery-Dreifuss muscular dystrophy 2, AD + 3 AR (LMNA)
• Allelic: Heart-hand syndrome, Slovenian type (LMNA)
• Allelic: Hutchinson-Gilford progeria (LMNA)
• Allelic: Hypospadias 1, XL (AR)
• Allelic: Leydig cell adenoma, somatic, with precocious puberty (LHCGR)
• Allelic: Lipodystrophy, familial partial, type 2 (LMNA)
• Allelic: Luteinizing hormone resistance, female (LHCGR)
• Allelic: Mandibuloacral dysplasia (LMNA)
• Allelic: Muscular dystrophy, congenital (LMNA)
• Allelic: Ovarian dysgenesis 5 (SOHLH1)
• Allelic: Pigmentary disorder, reticulate, with systemic manifestations, XL (POLA1)
• Allelic: Precocious puberty, male (LHCGR)
• Allelic: Premature ovarian failure 7 (NR5A1)
• Allelic: Prostate cancer, susceptibility to (AR)
• Allelic: Spinal + bulbar muscular atrophy of Kennedy (AR CAG)
• Acromesomelic dysplasia 3 (BMPR1B)
• Androgen insensitivity (AR)
• Androgen insensitivity, partial, with/-out breast cancer (AR)
• Fanconi anemia, complementation group A (FANCA)
• Galactosemia (GALT)
• Histiocytosis-lymphadenopathy plus syndrome (SLC29A3)
• Hypogonadotropic/hypergonadotropic hypogonadism 24 without anosmia (FSHB)
• Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
• Leydig cell hypoplasia with pseudohermaphroditism (LHCGR)
• Malouf syndrome: Cardiomyopathy dilatated with hypergonadotropic hypogonadism (LMNA)
• Microcephaly 1, primary, AR (MCPH1)
• Short stature, microcephaly + endocrine dysfunction (XRCC4)
• Spermatogenic failure 32 (SOHLH1)
• Spermatogenic failure 8 (NR5A1)
• Van Esch-O'Driscoll syndrome (POLA1)