Kallmann syndrome with FGFR1 and KAL1 mutations detected during fetal life

Abstract

Kallmann syndrome (KS) patients carrying FGFR1 mutations can transmit the disorder to their offspring as can asymptomatic female carriers of mutations in KAL1. We describe for the first time two cases in which KS was suspected during fetal life because of the family context and malformation detection by fetal ultrasound: syndactyly or unilateral renal agenesis in subjects with respectively FGFR1 and KAL1 mutations. In relevant family history, ultrasound monitoring can detect KS associated signs before birth and thus enable neonatal diagnosis and early management. These observations also underline the importance of genetic counselling for patients who may transmit KS to their offspring.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0287-9) contains supplementary material, which is available to authorized users.

Fibroblast growth factor 2 regulates activity and gene expression of human post‐mitotic excitatory neurons

“…; Sarfati et al . ). The precise mechanism remains unclear but the functional interaction has been shown in developing optic nerve and olfactory neuroblasts (Hu et al .…”

GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing

“…In a family that has variable phenotypes associated with the same mutation, patients and their relatives may be able to better understand this variability. In contrast, it is more difficult to explain the variable penetrance and expression of a form with possible AD inheritance of a de novo mutation (131)(132)(133). As mentioned, de novo mutations of FGFR1 and CHD7 can be frequent (2,12,69,(119)(120)(121)133 and Bouligand Young unpublished results).…”

“…If this is planned, adequate coordination with pediatricians should be put in place to ensure this critical window is not missed (2,6,131). Therapeutically effort should be made to elicit the patients' values during these encounters, provide accurate data and support or enable them to make informed decisions that are in line with their value system.…”

“…Thus, it is equally likely that a patient may opt for genetic screening yet will not obtain a result of a rare variant in a identified CHH/KS gene. This may be mitigated in some instances as hormone profiling of neonates during the mini-puberty (first 6-month of life) can biochemically determine if CHH/KS has been transmitted to the offspring (6,131).…”

“…In pedigrees indicating AD transmission, patients and their families should be informed that the risk of transmitting the mutation is 50% (26,131,69,74), but often the phenotype and severity are much more difficult to predict with accuracy. In a family that has variable phenotypes associated with the same mutation, patients and their relatives may be able to better understand this variability.…”