Kallmann Syndrome and X-linked Ichthyosis Caused by Translocation Between Chromosomes X and Y: A Case Report
A 20 year old male () was referred to the department of medical genetics of a tertiary care institute on the 16th of June, 2018. His chief complaints were delayed secondary sexual characteristics, impaired sense of smell, and poor scholastic performance. He was born of nonconsanguineous marriage. Family history was not significant. His weight was 60 kg (0 SD) and height was 151 cm (<−3 Z score). He had narrow palpebral fissures, eunuchoid appearance, gynecomastia, and sexual maturity rating corresponded to Tanner stage 3. His right testis was not identified in the scrotum or inguinal canal and left testicular volume was low (12 ml). Stretched penile length was 3.6 cm (<3rd centile). Mild ichthyosis on abdomen () and back was observed. He did not have any significant facial dysmorphism or any other malformation. Central nervous system examination revealed hyposmia, hoarse voice, and synkinesia of hands.\nEndocrinological evaluation was suggestive of hypogonadotrophic hypogonadism [FSH: 0.733 IU/L, LH: <0.1 IU/L (normal value: 1.7–8.6) and testosterone: 5.59 nmol/L (normal value: 8.6–29)]. Skeletal survey did not reveal any significant findings. Karyotype from peripheral blood lymphocytes was performed and an extra material on p arm of chromosome X was identified (46,Xp+,Y) (). DNA was extracted from peripheral blood and cytogenetic microarray was performed by Cytoscan 750 K array kit (Affymetrix, USA). A 8.3 Mb deletion on short arm of chromosome X {arr[hg19] Xp22.33p22.31(168,551–8,538,809)} including 37 OMIM genes and a 12.8 Mb duplication on long arm of chromosome Y {arr[hg19] Yq11.221q11.23(15,999,473–28,799,654)}including 25 OMIM genes were identified (). The breakpoint on X chromosome resulted in deletion of important and clinically relevant genes including ANOS1 (KAL1) gene (7th–14th exon), STS gene, and 4 other genes including SHOX, ARSL (ARSE), NLGN4X, and VCX (). The duplicated Y segment contained only one clinically important gene namely, DAZ1. Duplication of DAZ1 has not been implicated in any disease causation. Parental blood samples were not available to identify the inherited characteristics of this chromosomal aberration. However, both parents were clinically normal and fertile.