The cloverleaf skull

A patient presented with the cloverleaf skull, or Kleeblattschadel abnormality. He had a typical trilobed skull with synostosis and a honeycomb appearance on roentgenograms. He had no extracranial skeletal anomalies. The infant died at 1 month of age.     

Patient with craniosynostosis and marfanoid phenotype (Shprintzen-goldberg syndrome) and cloverleaf skull

Marfanoid phenotype with craniosynostosis (Shprintzen-Goldberg syndrome) is a rare disorder previously described in only 5 patients. We report on the sixth known patient with this condition. The findings which distinguish our patient from others reported previously are that she was ascertained prenatally as having a cloverleaf skull; this is the first female patient described with this condition. Postnatally, she presented with arachnodactyly, camptodactyly and cloverleaf skull. Imaging studies of the brain documented microcephaly with malformed brain, hydrocephaly, and hypoplasia of the corpus callosum. She also had choanal atresia and stenosis, a clinical finding previously reported only once, in this disorder. © 1995 Wiley-Liss, Inc.     

Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association

We report on a case of cloverleaf skull deformity in a patient with hypochondroplasia, a disorder which has not been previously associated with this anomaly. Hypochondroplasia is a bone dysplasia caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Cloverleaf skull is a trilobar skull deformity which is etiologically and genetically heterogeneous and occurs in association with a number of disorders which result from mutations in the fibroblast growth factor receptor genes.
Our patient demonstrated one of the common FGFR3 mutations identified in hypochondroplasia, a C-to-A change at nucleotide 1620 (C1620A) in the tyrosine kinase domain. The occurrence of a cloverleaf skull deformity appears to represent an example of variable expressivity in hypochondroplasia and suggests that additional factors other than a specific mutation can modify the phenotype in this disorder. In addition, identification of another FGFR mutation associated with cloverleaf skull further illustrates the genetic heterogeneity of this anomaly.     

Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: Prenatal diagnosis,clinical and pathological findings

We present male monozygotic twins with thanatophoric dysplasia (TD) type I concordant for long bone abnormalities and discordant for cloverleaf skull. The twins were the product of the second pregnancy of unrelated parents, with advanced paternal age. Prenatal diagnosis and postmortem examination showed severe rhizomelic shortness of limbs, bowing of the long bones with “telephone-receiver” femora in both twins, and cloverleaf skull and hydrocephalus in one of them. It is now accepted that most of cases of TD, such as in the present report, represent an autosomal dominant mutation with a high new mutations rate.     

Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: prenatal diagnosis, clinical and pathological findings.

We present male monozygotic twins with thanatophoric dysplasia (TD) type I concordant for long bone abnormalities and discordant for cloverleaf skull. The twins were the product of the second pregnancy of unrelated parents, with advanced paternal age. Prenatal diagnosis and postmortem examination showed severe rhizomelic shortness of limbs, bowing of the long bones with "telephone-receiver" femora in both twins, and cloverleaf skull and hydrocephalus in one of them. It is now accepted that most of cases of TD, such as in the present report, represent an autosomal dominant mutation with a high new mutations rate.     

Familial lethal skeletal dysplasia with cloverleaf skull and multiple anomalies of brain,eye, face and heart: a new autosomal recessive multiple congenital anomalies syndrome

We report on a 'new' lethal familial short-limb bone dysplasia associated with multiple anomalies in three sibs born to Arabic-Muslim consanguineous healthy parents. Clinical abnormalities included short limbs and short hands, cloverleaf skull, frontal bossing, wide anterior fontanel, hypertelorism, bilateral microphthalmia, cataract, low-set ears, narrow chest, ambiguous genitalia, cardiac ventricular septal defect (VSD) and agenesis of the corpus callosum. Radiological abnormalities included cloverleaf skull, hypoplastic clavicles and scapulae, thin, wavy cupped ribs, flat vertebral bodies with coronal clefting and several unossified vertebral pedicles and hypo-ossification of the pubic bone. The main changes noted in the long bones consisted of short-bowed long bones with abnormal metaphyses and unossified epiphyses. Chondro-osseous morphology documented degenerating chondrocytes with disorganization of the hypertrophied cartilage and short disorganized columns of hypertrophied areas. An autosomal recessive mode of inheritance seems most likely.     

定位X射线侧位头颅片在诊断儿童阻塞性睡眠呼吸暂停低通气综合征中的价值

目的采用定位X射线侧位头颅片的检查技术,观察儿童阻塞性睡眠呼吸暂停低通气综合征的腺样体肥大及颅骨测量,评估该方法在评估腺样体肥大及对上颌骨及下颌骨发育影响的价值。方法选择2006年至2010年在河北医科大学第一医院治疗的腺样体肥大患儿65例,其中男性31例,女性34例;年龄6岁1个月～7岁4个月,平均年龄7.10岁。并发分泌性中耳炎12例,慢性鼻-鼻窦炎20例,明显发育迟缓13例。在定位X射线侧位头颅片上把腺样体肥大程度分为Ⅰ组(n=35)A/N≥0.76,Ⅱ组(n=30)A/N≤0.75;以病程的长短分为A组(n=41)病程在3年以上(包括3年),B组(n=24)病程3年以下。回顾性分析比较两种情况下两组的颅骨测量值。结果腺样体的体积越大,对患儿面颅骨发育的影响越明显,Ⅰ、Ⅱ组的∠SNA(84.15°±1.76°vs 82.18°±2.11°;P<0.01)、∠SNB(78.91°±1.35°vs 77.92°±1.97°;P<0.05)和∠ANB(5.18°±1.09°vs 4.25°±0.95°;P<0.01)差异均有统计学意义。患病时间越长对患儿面颅骨发育的影响越重,A、B组的∠SNA(84.02°±1.73°vs 81.89°±2.17°;P<0.01)、∠SNB(78.92°±1.36°vs 77.65°±1.99°;P<0.01)和∠ANB(5.06°±1.06°vs4.23°±1.03°;P<0.01)差异均有显著统计学意义。结论定位X射线侧位头颅片可以很好地显示和测量腺样体;腺样体肥大可明显影响颅骨的发育;颅骨发育异常的严重程度与腺样体的体积和病程持续时间有关。     

Chondroblastoma-like tumor of the skull in a patient with cardio-facio-cutaneous syndrome

Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder characterized by craniofacial deformities and heterogeneous cardiac and cutaneous manifestations. The condition is caused by de novo activating mutations in one of four genes encoding proteins involved in the RAS-MAPK signaling pathway; specifically BRAF, MEK1, MEK2, or KRAS. Variable malignancies have been reported in patients with CFCS. Herein we report a chondroblastoma-like lesion of the skull in a 20-year-old man with a clinical diagnosis of CFCS and a long-standing history of medically intractable epilepsy. Patients with CFCS have previously been noted to have poorly-defined giant cell lesions and this may be one such example.     

Postnatal brain and skull growth in an Apert syndrome mouse model

Craniofacial and neural tissues develop in concert throughout prenatal and postnatal growth. FGFR‐related craniosynostosis syndromes, such as Apert syndrome (AS), are associated with specific phenotypes involving both the skull and the brain. We analyzed the effects of the FGFR P253R mutation for AS using the Fgfr2^+/P253R Apert syndrome mouse to evaluate the effects of this mutation on these two tissues over the course of development from day of birth (P0) to postnatal day 2 (P2). Three‐dimensional magnetic resonance microscopy and computed tomography images were acquired from Fgfr2^+/P253R mice and unaffected littermates at P0 (N = 28) and P2 (N = 20).Three‐dimensional coordinate data for 23 skull and 15 brain landmarks were statistically compared between groups. Results demonstrate that the Fgfr2^+/P253R mice show reduced growth in the facial skeleton and the cerebrum, while the height and width of the neurocranium and caudal regions of the brain show increased growth relative to unaffected littermates. This localized correspondence of differential growth patterns in skull and brain point to their continued interaction through development and suggest that both tissues display divergent postnatal growth patterns relative to unaffected littermates. However, the change in the skull–brain relationship from P0 to P2 implies that each tissue affected by the mutation retains a degree of independence, rather than one tissue directing the development of the other. © 2013 Wiley Periodicals, Inc.     

Multiple congenital skull fractures as a presentation of Ehlers-Danlos syndrome type VIIC

We describe a newborn infant with multiple congenital skull fractures and intracranial hemorrhage. He also had multiple skin folds suggesting a connective tissue abnormality. Electron microscopy of the skin biopsy showed collagen abnormalities with a "hieroglyphic appearance." The analysis of the synthesis of collagen in the cultured dermal fibroblasts demonstrated an accumulation of procollagen I. Molecular analysis found a nonsense mutation Q225X in ADAMTS2 gene, which encodes procollagen I N-terminal proteinase. All these findings confirmed the diagnosis of Ehlers-Danlos syndrome type VIIC (MIM 225410). Family studies suggested a founder effect in Ashkenazi Jews originating from Belarus. Prenatal diagnosis in the subsequent pregnancy reassured the parents that the fetus was an unaffected carrier.     

Effects of aneuploidy on skull growth in a mouse model of Down syndrome

Adult craniofacial morphology results from complex interactions among genetic, epigenetic and environmental factors. Trisomy causes perturbations in the genetic programmes that control development and these are reflected in morphology that can either ameliorate or worsen with time and growth. Many of the specific changes that occur in Down syndrome can be studied in the Ts65Dn trisomic mouse, which shows direct parallels with specific aspects of adult craniofacial dysmorphology associated with trisomy 21. This study investigates patterns of craniofacial growth in Ts65Dn mice and their euploid littermates to assess how the adult dysmorphology develops. Three-dimensional coordinate data were collected from microcomputed tomography scans of the face, cranial base, palate and mandible of newborn (P0) and adult trisomic and euploid mice. Growth patterns were analysed using Euclidean distance matrix analysis. P0 trisomic mice show significant differences in craniofacial shape. Growth is reduced along the rostro-caudal axis of the Ts65Dn face and palate relative to euploid littermates and Ts65Dn mandibles demonstrate reduced growth local to the mandibular processes. Thus, the features of Down syndrome that are reflected in the mature Ts65Dn skull are established early in development and growth does not appear to ameliorate them. Differences in growth may in fact contribute to many of the morphological differences that are evident at birth in trisomic mice and humans.     

三叶接骨板治疗Pilon骨折

目的探讨三叶接骨板治疗Pilon骨折的疗效以及注意事项。方法2001年1月至2005年1月，共收治35例Pilon骨折患者，其中采用切开复何、二叶接骨板内固定术治疗并有完整随访资料的患者21例，其中男性18例，女性3例，年龄22～66岁，平均35岁；按照Ruedi和Allgower分型：Ⅰ型3例，Ⅱ型14例，Ⅲ型4例，开放性骨折6例，闭合性骨折15例，合并同侧腓骨骨折16例，合并其它损伤6例。结果随访时间6～20个月，平均11．5个月。20例患者骨性愈合，骨折临床愈合时间为10～21周，平均14.2周，创伤性关节炎2例：关节不同程度僵硬4例，无一例出现伤口感染。据Tornetta临床评估标准，本组优良率为81％。结论通过详细的术前评估、术中仔细操作、术后恰当的功能锻炼，开放复位、三叶接骨板内固定治疗Pilon骨折可获得较好的疗效。     

小切口、三叶钢板治疗肱骨近端骨折的临床疗效

目的 观察小切口、三叶草钢板结合植骨治疗肱骨近端移位骨折的临床疗效.方法 通过小切口,使用三叶草钢板结合植骨对62例肱骨近端移位骨折进行治疗,采用Neer分类和评定标准分析疗效.结果 60例获得平均19个月(6～33个月)随访.60例均骨性愈合,无畸形愈合,无肱骨头坏死.按Neer评分标准评分,优40例,良16例,可4例,总优良率为93.3％.结论 三叶草钢板内固定植骨治疗肱骨近端移位骨折符合AO内固定原则,固定牢靠,可早期功能训练,采用小切口减少创伤,术后功能恢复满意.     

Phocomelia,ectrodactyly, skull defect and urinary system anomaly: Schinzel-phocomelia syndrome?

This report describes a girl with phocomelia of the right upper limb, ectrodactyly, sacral hypoplasia and a large skull defect, but with normal growth and mental development. Ultrasonography and intravenous pyelography showed bilateral hydronephrosis and dilated ureters. We conclude that this patient may represent Schinzel-phocomelia syndrome with additional urinary tract anomalies.