Kallmann syndrome in a patient with congenital spherocytosis and an interstitial 8p11.2 deletion.
We describe the hitherto smallest interstitial 8p11.2 deletion in a patient with congenital spherocytosis, dysmorphic features, and growth delay in association with hypogonadotropic hypogonadism and anosmia. The latter features are characteristic for Kallmann syndrome. In contrast to the previously reported patients with 8p deletions, the present patient showed normal intelligence. Congenital spherocytosis is one of the most common hereditary hemolytic anemias. One of the three loci for congenital spherocytosis was assigned to chromosome 8p (located between 8p11.1 and 8p21) and mutations in or loss of the ankyrin-1 gene (ANK1) were identified. Molecular analysis confirmed the de novo loss of ANK1 in our patient. Kallmann syndrome, which is characterized by hypogonadotropic hypogonadism and anosmia, can be X-linked, autosomal dominant, or autosomal recessive. So far only the X-linked KAL1 gene has been identified. The present finding suggests an autosomal locus for Kallmann syndrome at 8p11.2. The simultaneous occurrence of congenital spherocytosis, Kallmann syndrome phenotype, dysmorphic features, and growth delay in this patient points to a new contiguous gene syndrome.
Vermeulen
Stefan
S
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium. Stefan.Vermeulen@rug.ac.be
Messiaen
Ludwine
L
Scheir
Petra
P
De Bie
Sylvia
S
Speleman
Frank
F
De Paepe
Anne
A
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D006130:Growth Disorders / Q000473:pathology; D006801:Humans; D017436:Kallmann Syndrome / Q000473:pathology*; D007621:Karyotyping; D008297:Male; D018895:Microsatellite Repeats; D013103:Spherocytosis, Hereditary / Q000473:pathology*; D013577:Syndrome