Clinical_Rounds_in_Endocrinology_Volume_II_-_Pediatric_Endocrinology

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61. What is Klinefelter’s syndrome?

Klinefelter’s syndrome (KFS) is characterized by small testes, gynecomastia,

long-leggedness, and learning disabilities in a phenotypic male with the pres-

ence of one Y chromosome and two or more X chromosomes. The most com-

mon karyotypic abnormality in patients with KFS is 47,XXY (80 %), while the

rest have mosaicism (46,XY/47,XXY) and higher-grade chromosomal aneu-

ploidies (48,XXXY and 49,XXXXY). However, detection of low-grade mosa-

icism in a male without any phenotypic features does not merit a diagnosis of

Klinefelter’s syndrome.

62. What are the variants of Klinefelter’s syndrome?

The most common variant of KFS is 47,XXY (80 %), while the rest have

mosaicism (e.g., 46,XY/47,XXY) and higher-grade chromosomal aneuploi-

dies (e.g., 48,XXXY). Hypergonadotropic hypogonadism is present in patients

with both classical KFS and in those with higher-grade chromosomal aneu-

ploidies; however, there are important differences in the clinical manifesta-

tions between these variants of KFS. The prevalence of congenital

malformations (skeletal and cardiac anomalies), learning disabilities, and

mental retardation are more in patients with higher-grade chromosomal aneu-

ploidies. In addition, patients with higher-grade chromosomal aneuploidies

are taller than those with classical KFS, except patients with 49, XXXXY who

have short stature.

63. What are the defects related to SHOX overdosage in Klinefelter’s syndrome?

Patients with KFS have two or more X chromosomes and at least one Y

chromosome. Each sex chromosome has two pseudoautosomal regions

(PAR 1 and PAR 2). PAR1 contains at least 24 genes, whereas there are only

4 genes in PAR2. SHOX is a gene present in PAR1 in both X and Y chromo-

somes. Genes present in PAR 1 region of X chromosome do not undergo

inactivation during lyonization. Therefore, patients with KFS have overdos-

age of SHOX genes, which results in tall stature (long-leggedness) and

skeletal abnormalities (scoliosis, kyphosis, pectus excavatum, and

clinodactyly).

64. How to differentiate between hypogonadotropic hypogonadism and hypergo-
    nadotropic hypogonadism?
    The presence of anosmia, synkinesia, midline defects, skeletal anomalies,
    cryptorchidism, micropenis, small soft testes, and eunuchoidal proportions
    points to the diagnosis of hypogonadotropic hypogonadism (idiopathic),

7 Delayed Puberty