Introduction Central congenital hypothyroidism (CCH) is a rare disorder that can be caused by X-linked mutations in the immunoglobulin superfamily member 1 (IGSF1) gene. Here, we describe four familial cases with a variable presentation due to a novel IGSF1 pathogenic variant. Case presentation In the index case, investigation at birth of suspected brain-lung-thyroid syndrome surprisingly revealed a central hypothyroidism. Next-generation sequencing (NGS) uncovered a novel IGSF1 pathogenic variant: a hemizygous single base duplication (G) resulting in a premature stop codon (NM_001555.4: c.2485dup, p.Ala829Glyfs*15). Further family investigations revealed missed neonatal CCH for the older brother who presented with prolonged jaundice (TSH 3.06 mUI/L, FT4 9.4 pmol/L, FT3 4.2 pmol/L). It also led to the diagnosis of CCH at 11 months of age for the younger brother, whose thyroid function was considered normal at birth. Neuropsychological evaluations showed no cognitive impairment for the eldest two brothers, but a slightly reduced processing-speed index compared with the other parameters for the oldest. Furthermore, a maternal uncle was diagnosed with biochemical CCH at 34 years of age, despite having few symptoms, and a complete work-up revealed prolactin deficiency and macroorchidism. Discussion This report of a rare case of neonatal CCH caused by IGSF1 deficiency highlights the importance of recognizing the neonatal signs of hypothyroidism to diagnose CCH as early as possible. Our results also show the importance of performing family genetic screening if a pathogenic variant is identified, to properly monitor carriers as CCH may develop over time. We suggest that these families should be followed up in the long-term to better understand the natural history of this syndrome and evaluate the need for hormone substitution.

Background A relative can be an asset in dealing with chronic illnesses, such as acromegaly, where quality of life is altered even after remission. However, it has been shown that quality of life of caregivers can also be impacted. Our main objective was to compare the perception of acromegaly in remission in the patient-relative dyad. Methods In this observational study, 27 patients in remission and relatives were first asked to complete quality of life, anxiety/depression and coping strategy questionnaires. Then, the patient’s body image and self-esteem were evaluated from both the patient’s and from the relative’s point of view using the same questionnaires with modified instructions. Results Relatives had overall an accurate estimation of patient body image using the Figure Rating Scale by Stunkard. However, there were wide variations between the patient’s and the relative’s responses regarding self-esteem and body perception. The quality of life of relatives was not altered and was significantly higher in the social domain than for the patient. Conclusions Our results show that relatives require education concerning all the steps involved in the management of acromegaly, as they likely do not fully understand the sequelae of acromegaly.