Multicystic dysplastic kidney and Kallmann's syndrome: a new association?

Deeb, Asma; Robertson, A; MacColl, Gavin; Bouloux, Pierre; Gibson, Mary; Winyard, Paul J D; Woolf, Adrian S.; Moghal, Nadeem; Cheetham, Tim

doi:10.1093/ndt/16.6.1170

Cited by 22 publications

(9 citation statements)

References 32 publications

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“…Second, multiple dysplastic kidney was detected in the neonatal period of case 2. To our knowledge, multiple dysplastic kidney has not been described in patients with proven KAL1 mutation (42). Thus, our results would expand the spectrum of renal lesion in KS.…”

Section: Clinical Features In Patients With Kal1 Mutationssupporting

confidence: 50%

Clinical Assessment and Mutation Analysis of Kallmann Syndrome 1 (KAL1) and Fibroblast Growth Factor Receptor 1 (FGFR1, orKAL2) in Five Families and 18 Sporadic Patients

Sato¹,

Katsumata²,

Kagami³

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

203

167

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We report on the clinical and molecular findings in 25 males and three females with Kallmann syndrome (KS) aged 10-53 yr. Ten males were from five families, and the remaining 15 males and three females were apparently sporadic cases. Molecular studies were performed for Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, also known as KAL2) by sequence analysis for all the coding exons, by PCR-based deletion analysis, and by fluorescence in situ hybridization (FISH) analysis, showing six novel and two recurrent intragenic KAL1 mutations in seven familial and four sporadic male cases and two novel intragenic FGFR1 mutations in two sporadic male cases. In addition, submicroscopic deletions at Xp22.3 involving VCX-A, STS, KAL1, and OA1 were identified in three familial cases and one sporadic male case affected by a contiguous gene syndrome. Clinical assessment in the 15 males with KAL1 mutations showed normal and borderline olfactory function in two males and right-side dominant renal lesion in seven males, in addition to variable degrees of hypogonadotropic hypogonadism (HH) in all the 15 males and olfactory dysfunction in 13 males. The two males with FGFR1 mutations had HH and anosmia and lacked other features. Clinical features in the remaining 11 cases with no demonstrable KAL1 or FGFR1 mutations included right renal aplasia in one female, cleft palate in one male, cleft palate and perceptive deafness in one male, and dental agenesis and perceptive deafness in one male, in addition to a variable extent of HH and olfactory dysfunction. The results suggest the following: 1) KAL1 mutations might be more prevalent in the Japanese patients than previously estimated in the Caucasian patients and can be associated with apparently normal olfactory function; 2) FGFR1 mutations account for approximately 10% of KS patients, as previously reported in the Caucasian patients, and can result in HH and olfactory dysfunction-only phenotype; and 3) renal aplasia, which is characteristic of KAL1 mutations, and cleft palate and dental agenesis, which are characteristic of FGFR1 mutations, can occur in patients without KAL1 and FGFR1 mutations.

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Section: Clinical Features In Patients With Kal1 Mutationssupporting

confidence: 50%

Clinical Assessment and Mutation Analysis of Kallmann Syndrome 1 (KAL1) and Fibroblast Growth Factor Receptor 1 (FGFR1, orKAL2) in Five Families and 18 Sporadic Patients

Sato¹,

Katsumata²,

Kagami³

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

203

167

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“…Interestingly ultrasound revealed five cases of bilateral cysts, more frequent in normosmic patients. Deeb et al (2001) described two cases of antenatally diagnosed multicystic kidneys in two brothers with KS features but without KAL1 mutations. Anosmin-1, encoded by KAL1 , immunolocalizes early in the ureteric bud brunches and has a role in mediating cell adhesion during growth of the mesonephric duct/ureteric bud lineage.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Olfactory and Other Developmental Anomalies in Patients with Central Hypogonadotropic Hypogonadism

Valle¹,

Vezzani²,

Rochira³

et al. 2013

Front. Endocrinol.

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Introduction: Hypogonadotropic hypogonadism (HH) is a heterogeneous disease caused by mutations in several genes. Based on the presence of hyposmia/anosmia it is distinguished into Kallmann syndrome (KS) and isolated HH. The prevalence of other developmental anomalies is not well established.Methods: We studied 36 patients with HH (31 males, 5 females, mean age 41.5), 9 with familial and 27 with sporadic HH (33 congenital, 3 adult-onset), by physical examination, smell test (BSIT Sensonics), audiometry, renal ultrasound, and magnetic resonance imaging of the olfactory structures.Results: Based on the smell test, patients were classified as normosmic (n = 21, 58.3%) and hypo/anosmic (n = 15, 41.6%). Hypoplasia/agenesis of olfactory bulbs was found in 40% of patients (10/25; 75% hypo/anosmic, 7.6% normosmic, p < 0.01, Fisher’s test). Remarkably, olfactory structures were normal in two anosmic patients, while one normosmic patient presented a unilateral hypoplastic bulb. Fourteen of 33 patients (42.4%) presented neurosensorial hearing loss of various degrees (28.5% hypo/anosmic, 52.6% normosmic, p = NS). Renal ultrasound revealed 27.7% of cases with renal anomalies (26.6% hypo/anosmic, 28.5% normosmic, p = NS). At least one midline defect was found in 50% of the patients (53.3% hypo/anosmic, 47.6% normosmic, p = NS), including abnormal palate, dental anomalies, pectus excavatum, bimanual synkinesis, iris coloboma, and absent nasal cartilage. Anamnestically 4/31 patients reported cryptorchidism (25% hypo/anosmic, 5.2% normosmic, p = NS).Conclusion: Hypo/anosmia is significantly related to anatomical anomalies of the olfactory bulbs/tracts but the prevalence of other developmental anomalies, especially midline defects and neurosensorial hearing loss, is high both in HH and KS and independent of the presence of anosmia/hyposmia. From the clinical standpoint KS and normosmic HH should be considered as the same complex, developmental disease.

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“…Dysplastic kidney has been associated with mutations in autosomal genes and with different syndromes, including Kallmann syndrome 1, an X-linked condition caused by mutations of the KAL1 gene at Xp22.32 [Deeb et al, 2001;Winyard and Chitty, 2008]. This gene was duplicated in our patient but also has been observed to be duplicated in several other cases without dyplastic kidney, suggesting that this phenotype is incompletely penetrant or arises from an alternative molecular etiology.…”

Section: Discussionmentioning

confidence: 57%

47, XY, +der(Y),t(X;Y)(p21.1;p11.2): A unique case of XY sex reversal

Zárate

Dwivedi

Bartel

et al. 2010

American J of Med Genetics Pt A

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Translocations involving the short arms of the X and Y chromosomes are rare and can result in a functional disomy of the short arm of the X chromosome, including the dosage-sensitive sex reversal (DSS) locus. A result of such imbalance may be sex reversal with multiple congenital anomalies. We present the clinical and cytogenetic evaluation of a newborn infant with DSS and additional clinical findings of minor facial anomalies, left abdominal mass, 5th finger clinodactyly, and mild hypotonia. The external genitalia appeared to be normal female. The infant had bilateral corneal opacities and findings suggestive of anterior segment dysgenesis. Ultrasonography showed a small uterus with undetectable ovaries, and a left multicystic dysplastic kidney. High-resolution chromosome analysis identified the presence of a derivative Y chromosome, 47,XY, +der(Y)t(X;Y)(p21.1;p11.2), which was confirmed by fluorescence in situ hybridization studies. Array CGH showed a 35.1 Mb copy number gain of chromosome region Xp22.33-p21.1 and a 52.2 Mb copy number gain of Yp11.2-qter, in addition to the intact X and Y chromosomes. Previously reported patients with XY sex reversal have not had DSS with corneal opacities, dysgenesis of the anterior segment of the eye, and unilateral multicystic dysplastic kidney. These findings represent a new form of XY sex reversal due to an Xp duplication.

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Multicystic dysplastic kidney and Kallmann's syndrome: a new association?

Cited by 22 publications

References 32 publications

Clinical Assessment and Mutation Analysis of Kallmann Syndrome 1 (KAL1) and Fibroblast Growth Factor Receptor 1 (FGFR1, orKAL2) in Five Families and 18 Sporadic Patients

Clinical Assessment and Mutation Analysis of Kallmann Syndrome 1 (KAL1) and Fibroblast Growth Factor Receptor 1 (FGFR1, orKAL2) in Five Families and 18 Sporadic Patients

Prevalence of Olfactory and Other Developmental Anomalies in Patients with Central Hypogonadotropic Hypogonadism

47, XY, +der(Y),t(X;Y)(p21.1;p11.2): A unique case of XY sex reversal

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