■已知钙敏感受体(CASR)基因的功能丧失变异与无症状性家族性低钙血症(FHH)到新生儿重度甲状旁腺功能亢进(NSHPT)的临床范围有关。纯合或复合杂合变体通常是导致严重新生儿形式的原因,而杂合变体导致良性形式。一种复发性致病变异,p.Arg185Gln,两种形式都有报道,处于杂合状态。该变体可以是从头发生的,或者可以从具有FHH的父亲遗传。NSHPT导致全球张力减退,未能茁壮成长,典型的X射线异常(弥漫性脱矿,骨折,干phy端不规则),和可能致命的急性呼吸窘迫。磷酸钙标志物显示严重的高钙血症,尿钙吸收异常,和甲状旁腺功能亢进为主要体征。经典治疗包括钙限制,过度水合,和双膦酸盐。不幸的是,这种疾病经常导致甲状旁腺切除术。最近,拟钙剂已经以可变的功效使用。NSHPT的功效似乎特别依赖于CASR基因型。
■我们描述了短肋骨男性的产前表现,最初怀疑有骨骼纤毛病.出生时,他出现了与致病性杂合子CASR变体相关的NSHPT,Arg185Gln,继承自拥有FHH的父亲。西那卡塞产后治疗是成功的。
■详尽的文献综述允许与所有报道的Arg185Gln病例进行比较,并假设西那卡塞的疗效取决于CASR基因型。这证实了系谱和父母病史在产前短肋骨表现中的重要性,并质疑在存在特定临床体征的情况下,在怀孕或产前CASR基因测序期间进行磷钙探索的可行性。实际上,它可以实现早期拟钙剂治疗,这在CASR变体Arg185Gln中可能有效。
UNASSIGNED: Loss-of-function variants in the calcium-sensing receptor (CASR) gene are known to be involved in a clinical spectrum ranging from asymptomatic familial hypocalciuric hypercalcemia (FHH) to neonatal severe hyperparathyroidism (NSHPT). Homozygous or compound heterozygous variants are usually responsible for severe neonatal forms, whereas heterozygous variants cause benign forms. One recurrent pathogenic variant, p.Arg185Gln, has been reported in both forms, in a heterozygous state. This variant can be a de novo occurrence or can be inherited from a father with FHH.NSHPT leads to global hypotonia, failure to thrive, typical X-ray anomalies (diffuse demineralization, fractures, metaphyseal irregularities), and acute respiratory distress which can be fatal. Phosphocalcic markers show severe hypercalcemia, abnormal urinary calcium resorption, and hyperparathyroidism as major signs.Classical treatment involves calcium restriction, hyperhydration, and bisphosphonates. Unfortunately, the disease often leads to parathyroidectomy. Recently, calcimimetics have been used with variable efficacy. Efficacy in NSHPT seems to be particularly dependent on CASR genotype.
UNASSIGNED: We describe the antenatal presentation of a male with short ribs, initially suspected having skeletal ciliopathy. At birth, he presented with NSHPT linked to the pathogenic heterozygous CASR variant, Arg185Gln, inherited from his father who had FHH. Postnatal therapy with cinacalcet was successful.
UNASSIGNED: An exhaustive literature review permits a comparison with all reported cases of Arg185Gln and to hypothesize that cinacalcet efficacy depends on CASR genotype. This confirms the importance of pedigree and parental history in antenatal short rib presentation and questions the feasibility of phosphocalcic exploration during pregnancy or prenatal CASR gene sequencing in the presence of specific clinical signs. It could in fact enable early calcimimetic treatment which might be effective in the CASR variant Arg185Gln.