IllnessPubertas praecox, central; differential diagnosis

NGS +

[Sanger]

Central pubertas praecox leads to premature sexual development in both sexes: affected girls show signs of puberty before the age of 8, boys before the age of 9. The signs include the development of pubic and underarm hair, a growth spurt, acne and bone maturation. Girls also develop breasts and have their first period. In boys, the penis and testicles grow and the voice breaks. After the early growth spurt, patients often stop growing prematurely and often remain smaller than expected according to their parents. Early development before peers can be emotionally difficult and lead to psychological and behavioral problems. The cause of central precocious puberty is often unknown. The most common known genetic cause of central precocious puberty is mutations in the MKRN3 gene, with girls being more severely affected than boys. LHCGR gene variants cause male-limited precocious puberty. Mutations in other genes are less common causes. Of the 2 MKRN3 gene copies, only the paternal copy is activated in the offspring via genomic imprinting. Central precocious puberty follows an autosomal dominant inheritance pattern. The molecular genetic diagnostic yield is not exactly known - a negative DNA test result cannot rule out the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1330/

• Alias: Central precocious puberty
• Allelic: 46XY sex reversal 2, dosage-sensitive (NR0B1)
• Allelic: Aldosteronism, glucocorticoid-remediable (CYP11B1)
• Allelic: Aromatase deficiency (CYP19A1)
• Allelic: Greig cephalopolysyndactyly syndrome (GLI3)
• Allelic: Hypogonadotropic hypogonadism 13 with/-out anosmia (KISS1)
• Allelic: Hypogonadotropic hypogonadism 8 with/-out anosmia (KISS1R)
• Allelic: Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
• Allelic: Leydig cell hypoplasia with pseudohermaphroditism (LHCGR)
• Allelic: Luteinizing hormone resistance, female (LHCGR)
• Allelic: McCune-Albright syndrome, somatic, mosaic (GNAS)
• Allelic: Osseous heteroplasia, progressive (GNAS)
• Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
• Allelic: Polydactyly, preaxial, type IV (GLI3)
• Allelic: Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
• Allelic: Pseudopseudohypoparathyroidism (GNAS)
• ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (CYP11B1)
• Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (CYP21A2)
• Adrenal hypoplasia, congenital (NR0B1)
• Allelic: Leukemia, juvenile myelomonocytic (NF1)
• Allelic: Watson syndrome (NF1)
• Aromatase excess syndrome (CYP19A1)
• Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency (CYP21A2)
• Hypothalamic hamartomas, somatic (GLI3)
• Leydig cell adenoma, somatic, with precocious puberty (LHCGR)
• Neurofibromatosis, familial spinal (NF1)
• Neurofibromatosis, type 1 (NF1)
• Neurofibromatosis-Noonan syndrome (NF1)
• Pallister-Hall syndrome (GLI3)
• Pituitary adenoma 3, multiple types, somatic (GNAS)
• Precocious puberty, central, 1 (KISS1R)
• Precocious puberty, central, 2 (MKRN3)
• Precocious puberty, male (LHCGR)