Dagmar l’Allemand's research while affiliated with Ostschweizer Kinderspital (KISPI) and other places

... However, CDGP clusters in families [39] and a further study revealed a degree of overlap between the genetics of CHH and CDGP [20]. These findings were confirmed in a recent study describing a somewhat shared genetic predisposition, even if a greater prevalence of CHH variants and oligogenic involvement were more typical of CHH patients [40]. Nevertheless, the main utility of contemporary genetic studies remains its use in family counseling once the diagnosis is established, rather than as a routine firstline test. ...

... In approximately 2/3 of the cases, this is due to a normal developmental variant called constitutional delay of growth and puberty (5), but this is an exclusion diagnosis and causes of pathologic hypogonadism should be explored. After ruling out general chronic or acute illnesses and primary testicular failure, the main differential diagnosis is central (or hypogonadotropic) hypogonadism, characterized by low testosterone secretion by the testes due to an impaired gonadotropin-releasing hormone (GnRH)/gonadotropin axis function (3,4,(6)(7)(8). The GnRH neurons originate from the olfactory placode during the first trimester in the human fetus and migrate to the hypothalamus, following the axon guidance of the vomeronasal nerve. Mutations in genes involved in GnRH neuron and olfactory nerve development result in Kallmann syndrome, where congenital central hypogonadism is associated with hyposmia or anosmia (4,7,8). ...

... Eighty-two patients with genotype-proven 3βHSD2 deficiency have been reported in the literature and 31 were female, of whom only one-third were reported to have ambiguous genitalia at birth, mostly having mild cliteromegaly. Twothirds of the reported female patients with 3βHSD2 deficiency had normal external genitalia, which may cause difficulty and delay in achieving a definitive diagnosis (21,22). In the present study, we provide further evidence that 3βHSD2 deficiency rarely causes ambiguous genitalia in females, even in cases with severely impaired 3βHSD2 activity. ...

... In children with central CH, especially those with MPHD, the abovementioned "medical burden" is likely to result in an impaired HRQoL, but studies on HRQoL in children with central CH (with or without MPHD) are lacking, as was shown in a recent systematic review (9). Impaired HRQoL has been described in closely related patients groups like patients with (isolated) GHD or ACTH A c c e p t e d M a n u s c r i p t 5 deficiency (10)(11)(12). In adult patients with central ACTH deficiency fatigue is a well-known problem, in addition to HRQoL impairment (12). ...

... 21 Investigation of the renin-aldosterone axis and use of USP in moderate or severe hyponatraemia and concurrent analysis of renin and aldosterone levels helps to confirm the diagnosis or exclude genetic causes of hyponatraemia such as aldosterone synthase deficiency. 22 Following restoration of normal electrolytes off treatment, USP can be used to demonstrate a return to normality. ...