Unusual presentation of Kallmannn syndrome with contiguous gene deletion in three siblings of a family.

[kallmann syndrome]

We report the case of 3 brothers aged 34 , 24 , and 22 years , unmarried , who presented to our endocrinology clinic with absence of secondary sexual characters . There was no such history in other siblings , but their maternal uncle had similar complaints . On examination , all 3 had pre-pubertal appearance , voice , and genitalia along with anosmia and bimanual synkinesia . Cryptorchidism was noticed in 2 while third person had small hypoplastic testes . It was also noted that all 3 patients had icthyosis mainly involving trunk , back , and limbs . The hormonal assays were consistent with isolated hypogonadotrophic hypogonadism . IQ testing revealed mental retardation in the 2 patients . Ultrasound showed ectopic right kidney in one patient , atrophic right kidney in the second patient while the third patient had normal kidneys . MRI brain of all the patients showed poorly visualized olfactory tract and bulb . Kallmann syndrome (KS ) was diagnosed based on hormonal evaluation and MRI results . Of the four types of KS : Synkinesia , renal anomaly , and X-linked pedigree pattern in our patients pointed towards X-linked type 1 KS as the possible cause . But , icthyosis and mental retardation are not usual presentation of type 1 KS . They are usually seen as a result of contiguous gene deletion of KAL 1 , steroid sulfatase (STS ), and mental retardation (MRX ) gene on X chromosome . Hence , the possible gene defect in our cases is inherited defect in contiguous gene deletion . The contiguous gene deletion as the cause of KS in 3 patients of same family is very rare and worth reporting . Also , the significance of phenotype-genotypic association in Kallmann syndrome is discussed .

Diseases
Validation

Diseases presenting "mental retardation" symptom

achondroplasia

alexander disease

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

classical phenylketonuria

coats disease

cohen syndrome

cowden syndrome

cystinuria

dentin dysplasia

familial hypocalciuric hypercalcemia

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

monosomy 21

phenylketonuria

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

sneddon syndrome

triple a syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated