背景:纹状体骨病合并颅骨硬化(OS-CS),也被称为霍兰-贝顿综合征,是一种罕见的遗传病;迄今为止已经报道了大约90例。它与AMER1基因的突变(女性受试者为杂合,男性为半合子)有关,位于Xq11.2,并显示了X链接的传输模式。典型的临床表现包括大头畸形,特征性面部特征(正面凸起,后背褶皱,超端粒,鼻梁凹陷,口面裂痕,突出的下巴),听力损失和发育迟缓。男性通常表现出比女性更严重的表型,很少存活。诊断怀疑是基于临床症状,颅骨和长骨硬化和干phy端条纹的影像学发现,随后的基因检测可能会证实这一点。
方法:特此,我们报道了一名女性新生儿的额叶和顶叶,狭窄的双颞孔直径,发育不良,低设定和向后旋转的耳朵,微回颌,腭裂,和下肢根茎缩短。出生后,她表现为喂养不耐受,胆道呕吐和腹胀。因此,怀疑是肠梗阻,她接受了手术,证明并纠正了肠旋转不良。四肢X射线和颅骨计算机断层扫描检查未显示颅骨硬化和/或干phy端条纹。Array-CGH分析显示正常发现。然后,目标下一代测序(NGS)分析,包括与骨骼发育不良有关的基因,进行并揭示了AMER1基因的从头杂合无义突变。患者在2月龄时出院,并纳入多学科随访。9个月大,她现在表现出发育和生长延迟(相对大头畸形除外)。腭裂的手术矫正已计划。
结论:我们的报告显示,女性新生儿肠旋转不良与OS-CS的相关性并不常见。它强调了新生儿学家必须考虑这样的诊断,即使没有颅骨硬化和长骨条纹,这些通常随着时间的推移而出现。与颅骨畸形和骨骼发育不良的其他综合征必须包括在鉴别诊断中。表型谱在两种性别中都是广泛且可变的。由于可变的X失活,女性也可能表现出严重和早发性的临床表现。多学科管理和细心,应该对这些患者进行早期和长期随访,以便及时识别任何相关的发病率,并防止可能的并发症或不良后果。
BACKGROUND: Osteopathia Striata with Cranial Sclerosis (OS-CS), also known as Horan-Beighton Syndrome, is a rare genetic disease; about 90 cases have been reported to date. It is associated with mutations (heterozygous for female subjects and hemizygous for males) of the AMER1 gene, located at Xq11.2, and shows an X-linked pattern of transmission. Typical clinical manifestations include macrocephaly, characteristic facial features (frontal bossing, epicanthal folds, hypertelorism, depressed nasal bridge, orofacial cleft, prominent jaw), hearing loss and developmental delay. Males usually present a more severe phenotype than females and rarely survive. Diagnostic suspicion is based on clinical signs, radiographic findings of cranial and long bones sclerosis and metaphyseal striations, subsequent genetic testing may confirm it.
METHODS: Hereby, we report on a female newborn with frontal and parietal bossing, narrow bitemporal diameter, dysplastic, low-set and posteriorly rotated ears, microretrognathia, cleft palate, and rhizomelic shortening of lower limbs. Postnatally, she manifested feeding intolerance with biliary vomiting and abdominal distension. Therefore, in the suspicion of bowel obstruction, she underwent surgery, which evidenced and corrected an intestinal malrotation. Limbs X-ray and skull computed tomography investigations did not show cranial sclerosis and/or metaphyseal striations. Array-CGH analysis revealed normal findings. Then, a target next generation sequencing (NGS) analysis, including the genes involved in skeletal dysplasias, was performed and revealed a de novo heterozygous nonsense mutation of the AMER1 gene. The patient was discharged at 2 months of age and included in a multidisciplinary follow-up. Aged 9 months, she now shows developmental and growth (except for relative macrocephaly) delay. The surgical correction of cleft palate has been planned.
CONCLUSIONS: Our report shows the uncommon association of intestinal malrotation in a female newborn with OS-CS. It highlights that neonatologists have to consider such a diagnosis, even in absence of cranial sclerosis and long bones striations, as these usually appear over time. Other syndromes with cranial malformations and skeletal dysplasia must be included in the differential diagnosis. The phenotypic spectrum is wide and variable in both genders. Due to variable X-inactivation, females may also show a severe and early-onset clinical picture. Multidisciplinary management and careful, early and long-term follow-up should be offered to these patients, in order to promptly identify any associated morbidities and prevent possible complications or adverse outcomes.