Ocular malformations and lissencephaly

Retinal dysplasia and agyria without cortical lamination are the constant findings in this autosomal recessive syndrome. There may also be anterior chamber malformations, cataract, and microphthalmos. Brain autopsies have shown a variety of associated malformations such as posterior encephalocele, Arnold-Chiari malformation, agenesis of the septum pellucidum and of the corpus callosum, agenesis of the vermis and hypoplasia of the cerebellum. Muscular dystrophy is probably present in most of these patients. Within the last few years, over 20 cases with a complete autopsy have been described. The syndrome should be differentiated from other syndromes with retinal non-attachment and retinal dysplasia, and from syndromes with hydrocephalus or encephalocele without these ocular features.     

儿童外表畸形与疾病

一些遗传性或某些药物引发的先天性疾病,通常伴有各种颅面、皮肤、肢体畸形.及早发现这些畸形,可以为临床诊断提供有效的帮助.该文主要探讨颅面、皮肤、肢体可以被观察到的畸形及与常见综合征、代谢性疾病或基因有关疾病相关的特殊体征.     

儿童外表畸形与疾病

一些遗传性或某些药物引发的先天性疾病,通常伴有各种颅面、皮肤、肢体畸形.及早发现这些畸形,可以为临床诊断提供有效的帮助.该文主要探讨颅面、皮肤、肢体可以被观察到的畸形及与常见综合征、代谢性疾病或基因有关疾病相关的特殊体征.     

儿童外表畸形与疾病

一些遗传性或某些药物引发的先天性疾病,通常伴有各种颅面、皮肤、肢体畸形.及早发现这些畸形,可以为临床诊断提供有效的帮助.该文主要探讨颅面、皮肤、肢体可以被观察到的畸形及与常见综合征、代谢性疾病或基因有关疾病相关的特殊体征.     

Greig cephalopolysyndactyly syndrome.

Based on the family presented and five others previously described, it can be concluded that the Grieg cephalopolysyndactyly syndrome is a fully penetrant autosomal dominant disease consisting of four variably expressed malformations: postaxial polydactyly (type B), preaxial polydactyly, syndactyly, and minor craniofacial abnormalities. This entity can be differentiated from other craniofacial-digital syndromes because of the absence of mental retardation, craniosynostosis, and brachydactyly.     

Association of assisted reproductive technology with twinning and congenital anomalies

Recently many reports have been published on the use of intracytoplasmic sperm injection (ICSI) and the increased risk of congenital major malformations or syndromes. We present three cases with Goldenhar syndrome (one of them a twin pair) and one case with Rubinstein-Taybi syndrome (RTS), also a twin pair. All four female cases are derived from ICSI. Goldenhar syndrome with ICSI pregnancy has been reported previously but as far as we know, RTS has not been described in association with assisted reproductive technology (ART). The four new cases reported herein will contribute to a better understanding whether ICSI pregnancy increases congenital malformations.     

Rectal duplications accompanying rectovestibular fistula: Report of two cases

Rectal duplication (RD) cysts are rare congenital anomalies that can be diagnosed with the presence of another opening in the perineum. They seldom accompany anorectal malformations (ARM). Two cases of RD accompanying ARM at opposite ends of the phenotypic spectrum, are described. A 3‐month‐old baby and a 2‐year‐old girl with ARM were scheduled for posterior sagittal anorectoplasty. The infant had an orifice at the anal dimple and the other had an orifice at the vestibulum posterior to the rectovestibular fistula. The infant presented with no other anomalies whereas the older one presented with an unusual coexistence of caudal duplication and caudal regression syndromes. Perioperatively both orifices were found to be related to retrorectal cysts, and were excised. Clinicians should always be alert when dealing with complex malformations. Because these malformations have variable anatomical and clinical presentations, they can represent a diagnostic and therapeutic challenge.     

Renal dysplasia with multisystem malformation—A Study of 9 Cases

Nine cases of renal dysplasia encountered in a review of necropsy material are described. All these cases had associated major and minor malformations of other systems. Three out of four cases identifying with ‘prune belly’ syndrome had lower urinary tract obstruction. Three cases fulfilled the criteria of Meckel’s syndrome. Three of these six cases, in addition, showed overlapping features with other syndromes. Three cases of unilateral dysplasia with contralateral agenesis had associated anomalies not conforming to any definite combination. We suggest that the association of malformations of developmentally unrelated systems may be random, not sharing any feature except being incompatible with life.     

The role of upper airway endoscopy in craniofacial malformations

ObjectiveTo study the role of upper airway endoscopy (UAE) in craniofacial malformations in all different management approaches described in the literature.MethodsA narrative review was performed, based on a search in pubmed.ResultsUAE use was reviewed over five domains: 1) Diagnosis of glossoptosis and endoscopic classification: drug-induced sleep endoscopy is recommended to graduate tongue base obstruction; there is still no consensus on the graduation system to be used. 2) Airway abnormalities: there is a high incidence of additional lesions in conjunction with glossoptosis. 3) Swallowing evaluation: a formal comparison with fluoroscopy (gold standard) has not yet been performed in this population. 4) Intubation: thin bronchoscopes allow intubation of small babies; moreover, intubation with rigid video-assisted laryngoscopes show a high success rate in this population. 5) Treatment outcome monitoring: there is no consensus on the ideal parameters to be checked.ConclusionSome approaches have already been well established in the management of patients with craniofacial malformations, e.g. the endocopic evaluation of glossoptosis and associated lesions and its role as an intubation assistance tool, while others need to be subject of further research, e.g. its role in swallowing investigation and as a postoperative success control predictor.     

Apert 综合征 1 例临床特征与基因类型分析

目的分析Apert综合征(AS)临床特征与基因类型。方法回顾1例AS患儿的临床资料及患儿和其父亲FGFR2基因测序结果,并复习相关文献。结果男性患儿,1岁1个月,扁头,突眼,眼距宽,耳位低,下颌小,高腭弓,无腭裂,双手五指并指并挛缩,双足五趾并趾。FGFR2基因外显子7 c.758CG,p.P253R杂合变异,父亲未检测到相关基因突变,支持Apert综合征诊断。文献检索到AS个案24例,22例明显颅面部畸形,1例轻微畸形,1例无畸形;均有手足并指/趾畸形。基因类型为S252W 13例,P253R 3例,Alu元件插入3例,基因缺失2例,杂合突变2例,序列变异1例。结论 AS患儿颅面部畸形及手足并指/趾明显,FGFR2基因以S252W、P253R突变为主。     

48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome

Sex chromosome tetrasomy and pentasomy conditions occur in 1:18,000-1:100,000 male births. While often compared with 47,XXY/Klinefelter syndrome because of shared features including tall stature and hypergonadotropic hypogonadism, 48,XXYY, 48,XXXY and 49,XXXXY syndromes are associated with additional physical findings, congenital malformations, medical problems and psychological features. While the spectrum of cognitive abilities extends much higher than originally described, developmental delays, cognitive impairments and behavioural disorders are common and require strong treatment plans. Future research should focus on genotype-phenotype relationships and the development of evidence-based treatments. CONCLUSION: The more complex physical, medical and psychological phenotypes of 48,XXYY, 48,XXXY and 49,XXXXY syndromes make distinction from 47,XXY important; however, all of these conditions share features of hypergonadotropic hypogonadism and the need for increased awareness, biomedical research and the development of evidence-based treatments.     

New chromosomal dysmorphic syndromes

This is the report of two independent families in which a balanced maternal translocation led to trisomy 12p in one of each their offspring. Evaluation of 21 further case reports indicates that this is a phenotypically well defined syndrome which leads to severe developmental retardation. It can be recognized by a characteristic combination of craniofacial anomalies which are summarized in a phantom picture. The gene sequences which produce the typical features in the trisomic state must be localized distally to band 12p 12, which is the breakpoint in the partial trisomies. The specific craniofacial anomalies are not visibly modified by the length of the trisomic segment or additional small monosomies or trisomies of recipient chromosomes. However, the frequency and severity of organ malformations and the resulting probability of survival seem to decrease with increasing degrees of chromosomal imbalance. A cytogenetic classification of the 21 inherited translocations and a segregation analysis from the pedigree data was performed. For the different types of translocations the calculated risk figures are given.     

Proteus syndrome versus Bannayan-Zonana syndrome: a problem in differential diagnosis

The Proteus syndrome (PS) and the Bannayan-Zonana syndrome (BZS) both have multiple hamartomata as prominent features. Hemihypertrophy, macrodactyly, exostoses, skin lesions, scoliosis, and sporadic occurrence are seen in PS, whereas patients with BZS have macrocephaly and related craniofacial findings. BZS has been observed in families as an autosomal dominant trait. Although the two syndromes can be distinguished in most patients, there are features in common to both that may pose a diagnostic dilemma in an isolated case. We report the case of a 3-year-old girl with macrocephaly, macrodactyly, and superficial and intra-abdominal hamartomata who illustrates the problem of differentiating recently reported patient with other published cases of PS and BZS. Patients with PS, in general, show more extensive systemic involvement, including skeletal and cutaneous manifestations. Macrocephaly, seen in all reported patients with BZS, is also found in 14% of patients with PS. Overlap among syndromes which include hamartomata as prominent features suggests that they might be etiologically or pathogenetically related. The present case also illustrates the usefulness of imaging techniques in the diagnosis of mixed mesodermal hamartomata.Abbreviations PS Proteus syndrome - BZS Bannayan-Zonana syndrome - OFC occipito-frontal circumference - CT computed tomography - MRI magnetic resonance imaging     

Nasal dermoid sinus cyst: accidental coincidence or syndrome association?

BACKGROUND: Peters anomaly is a rare congenital glaucoma disease. The Peters' plus syndrome is characterized by distinct malformations. As some of the common craniofacial malformations like cleft lip and palate are frequent in Peters' plus syndrome, no nasal dermoid sinus cysts has been reported so far. Nasal dermoid sinus cysts usually present in isolation, although associations to other anomalies or syndromes are possible. The occurence of such an anomaly may be either accidental, or present a syndrome association. PATIENTS AND METHOD: One patient with an unilateral cleft lip and Peters' plus syndrome had undergone removal of nasal dermoid sinus cyst previously and was referred for management of recurrent disease. Complete surgical removal and plastic reconstruction was performed. RESULTS: Concerning the common (lateral) cleft lip nasal deformity with no midline nasal masses, there are reasons for the assumption that a coincidence of both anomalies might be accidental. Especially in Peters' plus syndrome no occurrence of nasal dermoids has thus far been documented. However, the embryological pathway of the frontonasal region differs from lip and palate development in time and location: So unique formation of both lesions seems inconsistent. Complete surgical removal and plastic reconstruction simultaneously or in a second step are recommended. CONCLUSION: As two cases of arhinia and Peters anomaly have been described in 1978, midline nasal masses might be a possible appearance of Peters' plus syndrome.     

Alobar holoprosencephaly,diabetes insipidus and coloboma without craniofacial abnormalities: a case report

An infant is described with coloboma of the right eye, holoprosencephaly and diabetes insipidus without craniofacial malformations. The association is discussed in view of the development of the prosencephalon and its relation to the development of craniofacial structures.     

Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi‐detector row computed tomography

Costello syndrome is a rare multiple congenital anomaly syndrome caused by heterozygous germline HRAS mutations, which is characterized by intellectual disability, growth retardation, distinctive facies, loose skin, cardiomyopathy and a preposition to malignancies. Although teeth abnormalities have been encountered in nearly two‐thirds of the patients in literature, the evaluation tended to be limited to the extent which can be obtained from physical examination. We investigated detailed craniofacial, oral and dental findings in four patients with Costello syndrome. In this study, images reconstructed by multi‐detector row computed tomography (MDCT) were used as substitutes for dental cast study and panoramic and lateral cephalometric radiograph studies to evaluate dental arches, tooth size, relationships between craniofacial and dental structures, and hypodontia. All four patients showed true/relative macrocephaly with facial bone hypoplasia and gingival hypertrophy. Occlusal attrition, malocclusion, small dental arches, microdontia, and convex face were noted in three patients. In addition, one patient showed dental caries, conic tooth and gingivitis, and another patient showed hypodontia. Our study suggests that craniofacial and dental abnormalities are common in Costello syndrome patients and comprehensive dental care should be provided from early infancy. To our knowledge, this is the first study of thorough craniofacial and dental evaluation by using MDCT in Costello syndrome. MDCT is a useful tool for precise evaluation of craniofacial and oral manifestations in patients with congenital anomaly/intellectual disability syndromes.     

M?bius and M?bius-like syndromes (TTV-OFM, OMLH)

There exists a spectrum of syndromes characterized by cranial nerve palsies, limb anomalies, and craniofacial malformations. Criteria based on type and severity of limb anomaly or presence or absence of cranial nerve palsy may alter the syndrome nomenclature due to a selection bias but do not appear to benefit syndrome delineation to any extent. Patients with seventh nerve palsy and abduction weakness are usually diagnosed as having M?bius syndrome by ophthalmologists. The observed ocular motility findings range from primarily abduction deficiencies to patients who have a Duane or gaze palsy pattern of horizontal movements. Some cases previously described as "sixth nerve and partial third" may better fall into one of the latter groups, since an isolated adduction deficit as a manifestation of third nerve involvement is rare. The presence of clinical appearance of Duane syndrome in these M?bius-type patients raises the possibility of abnormal innervation of the lateral rectus as an explanation of some patterns of motility observed.     

Polysyndaktylie,verkürzte Gliedmaßen und Genitalfehlbildungen: Kennzeichen eines selbständigen Syndroms?

4 newborn babies dying shortly after birth exhibited severe malformations including median cleft lip, excessive polysyndactyly, short ribs and limbs, genital abnormalities, and anomalies of epiglottis and visceral organs. 13 nearly identical cases were found in the literature. In addition, 19 similar cases have been described. They all probably represent a separate, previously unrecognized syndrome. This peculiar association of congenital malformations can be clearly delineated from 12 syndromes, which share more or less similar features. The etiology is unknown.     

Micronutrients and Congenital Anomalies*

Abstract: Insufficient as well as excessive amounts of essential micronutrients such as vitamins and minerals are known to be deleterious to developing embryos in mammals. However, no detailed analysis of the effects of biotin deficiency on mammalian embryos has been reported. We demonstrated that maternal biotin deficiency produced a high incidence of external and skeletal malformations in mice, although the dams showed no clinical signs of biotin deficiency during gestation. The prominent malformations were craniofacial and limb malformations such as cleft palate, micrognathia, and micromelia. A dose-response relationship was observed in the incidences of the respective malformations. The formation of secondary palatal processes and limb buds was delayed at midgestation in these biotin-deficient mouse embryos, probably leading later to cleft palate and limb malformations. When the teratogenicity of biotin deficiency was compared in three mammalian species, striking species and strain differences were detected. Excess retinoids are embryotoxic and teratogenic in mammals, causing especially high incidences of craniofacial and limb malformations. We examined the mechanism of action of retinoic acids (13-cis-, 4-oxo-13-cis-, and all-trans-) on the craniofacial tissues of mouse embryos using whole embryo culture and primary cell culture. In cultured embryos, retinoic acids caused overall embryonic growth retardation, particularly in the facial processes (maxillary, mandibular, and nasal). Histological examination of mouse embryos at midgestation showed that cranial neural crest cells were not migratory and demonstrated pyknotic nuclei in the mesenchyme adjacent to the epithelium in nasal processes. Biochemicalanalysis revealed that retinoic acids also inhibit DNA synthesis and the proliferation of mesenchymal cells in facial processes, a finding that is relevant to the mechanisms of retinoic acid-induced craniofacial malformations. It is proposed that the role of micronutrients in embryonic growth and development should be evaluated at the cellular level using whole embryo culture and embryonic cell culture.     

Cardiac problems in genetic syndromes

Congenital heart disease affects around 0.7% of liveborn infants and is the most frequent cause of death from congenital malformations. This review will consider some of the commoner genetic syndromes associated with congenital heart disease, the spectrum of cardiac defects observed in them and the associated features and comorbidities that may impact on the outcomes of cardiac surgery.