VACTERL association with a cleft hand

ABSTRACT  Regarding radial ray deficiency, several reports suggest that preaxial limb anomalies occur frequently, while postaxial limb anomalies and cleft hand (split–hands) are rarely associated with VACTERL. We describe a rare clinical case of VACTERL with cleft hand and a number of visceral anomalies.     

Unusual manifestations of VACTERL association

We report a case of VACTERL association along with unusual manifestations of pseudo-exostrophy of bladder, hemifacial microsomia and an urachal cyst communicating with the bladder.     

Inheritance of the VATER/VACTERL association

VATER/VACTERL association refers to the non-random co-occurrence of the following component features: vertebral defects, anal atresia, cardiac malformations, tracheoesophageal atresia, renal abnormalities, and limb defects. Recently, Solomon et al. (Hum Genet 127:731-733, 2010) observed an increased prevalence of component features among first-degree relatives of VATER/VACTERL patients suggesting that in some patients, the disorder may be inherited. To replicate these findings, we investigated 87 VATER/VACTERL patients with the presence of a minimum of three component features and their first-degree relatives (n = 271). No increase in the overall prevalence of component features was observed in first-degree relatives compared to the general population (χ2 = 2.68, p = 0.10). Separate analysis for the prevalence of single component features showed a higher prevalence of tracheoesophageal fistula/atresia among first-degree relatives compared to the general population (OR 17.65, 95% CI 2.47-126.05). However, this was based on occurrence in one family only. Our findings suggest that although familial occurrence renders a genetic contribution likely, the overall risk of recurrence among the first-degree relatives of patients with VATER/VACTERL association is probably very low. Since the patients in the present study were young and no offspring could be studied, estimation of the role of de novo mutations in the development of VATER/VACTERL was not possible.     

VACTERL association with Prune-Belly syndrome

We report a term, small for gestational age neonate having full spectrum of VACTERL association. In addition, the neonate also had triad of signs and symptoms associated with prune belly syndrome. The concurrence of these two syndromes could lie in their common etiology of defect in mesodermal differentiation. Such a combination is extremely rare and is generally incompatible with life.     

Familial occurrence of the VATER/VACTERL association

The acronym VATER/VACTERL association is used to describe the non-random co-occurrence of vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheo-esophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). We report a familial case of VATER/VACTERL association in which both the index case and her maternal uncle displayed four major component features of the disorder. A systematic literature search identified 12 previously described familial cases. However, on comparison, both members fulfilled the diagnostic criteria for VATER/VACTERL association only in one instance, and ours is the second such report. Although, a SNP array-based analysis identified no causal genomic alteration, the findings in the present family suggest that genetic factors are implicated in the development of the disorder.     

Clinical characteristics of neonates With VACTERL association

Background: The VACTERL association (VA) is the non‐random co‐occurrence of vertebral anomalies, anal atresia, cardiovascular malformations, tracheoesophageal fistula and/or esophageal atresia, renal anomalies, and/or limb anomalies, and is referred to by the first letters of its components. Studies investigating the clinical characteristics of VA patients and probing of the observed current six component types are limited, and none of them is focused on neonates. We investigated the clinical characteristics of our patients diagnosed as having VA in the newborn period. Methods: We retrospectively reviewed the neonates whose final diagnosis was VACTERL association. Presence of at least three components of previously reported six anomalies was accepted as VACTERL association. Sex, birthweight, gestational age, postnatal age, anomalies of the systems that are included in VA, and the other features were recorded. Results: There was a male predominance (14/11) of 28 patients; and there were three patients with ambiguous genitalia. The most common observed VACTERL component was vertebral anomalies (n= 26), followed by anal atresia (n= 19), tracheoesophageal fistula/esophageal atresia (n= 17), renal anomalies (n= 15), limb anomalies (n= 15) and cardiac anomalies (n= 14). The most frequent combination was VCTL (n= 4). Fifteen (57%) patients had non‐VACTERL anomalies and the most frequent of these was ambiguous genitalia (n= 3). Conclusion: VA patients may have different clinical characteristics in different populations, and clinicians may miss some component features if the patients are evaluated after the neonatal period.     

新生儿VACTERL联合征的临床与影像学表现

目的 分析新生儿VACTERL联合征的临床表现及影像学特点,提高对本病的认识和诊断水平.方法 选择2009年1月至2012年11月在本院放射科检查的食管闭锁和肛门闭锁患儿,按照VACTERL联合征的诊断标准,回顾X线影像资料,并分析患儿临床表现及影像学特点.结果 研究期间在本院放射科进行检查的食管闭锁和肛门闭锁患儿共38例,其中4例食管闭锁患儿符合VACTERL联合征的诊断.1例食管闭锁并气管食管瘘、胸椎半椎畸形、右侧第11肋骨缺如、多指畸形;1例食管闭锁并先天性心脏病（房间隔缺损、动脉导管未闭）、右心房右心室扩大、双手拇指畸形;1例食管闭锁并气管食管瘘、双侧第13肋骨、脊柱裂、左肾积水、右肾缺如;1例食管闭锁并气管食管瘘、先天性心脏病（室间隔缺损、动脉导管未闭）、左手赘指畸形.结论 新生儿VACTERL联合征临床和影像表现具有一定特点,临床和影像学检查结合可以做出该诊断.     

Rectum and bladder duplication with malformations of the VACTERL association

The case of a newborn with duplications of rectum, presenting as a tumor of the labia majora, and duplication of bladder and urethra is reported. In addition malformations from the VACTERL-association (sacral malformation, anal atresia with vestibulum fistula, renal dysplasia, only eleven pairs of ribs with hypoplasia of the eleventh one, diplopodia on the left foot) were found. In the study of urogenital and enteric duplications in cases from the literature this coincidence with VACTERL malformations was found as well.     

Monochorionic twin fetus with VACTERL association after intracytoplasmic sperm injection

We report a rare case of a monochorionic twin gestation after intracytoplasmic sperm injection (ICSI) in which one of the fetuses had VACTERL association. A 27‐year‐old woman became pregnant by ICSI and was found to have monochorionic twin fetuses. One fetus was noted to have the following anomalies: a multicystic, dysplastic left kidney with a hydroureter, and a dilated colon. A normal‐sized stomach and normal amount of amniotic fluid were observed during the prenatal period with no other anomalies. The postnatal examination revealed hypospadias, and anal, esophageal, and duodenal atresia; thus, a diagnosis of VACTERL association was established. Although the prenatal diagnosis of this disorder is a challenge, even in a singleton, some of the characteristic features observed during antepartum ultrasonography may be a clue to the diagnosis, especially in a twin pregnancy after ICSI.     

Townes syndrome. A distinct multiple malformation syndrome resembling VACTERL association

An 8-year-old male is presented with clinical findings of Townes syndrome in an otherwise unaffected family. Additional abnormalities possibly representing low frequency associations of this autosomal dominant multiple malformation syndrome included a cardiac defect and hypospadias. Similarities exist between Townes syndrome and VACTERL association, which is generally regarded to be sporadic in nature. Recognition of Townes syndrome as a distinct entity is critical for implementing appropriate management in early childhood, including amplification of hearing impairments. Variable expressivity may occur in this disorder. Careful evaluation must be made, therefore, of the parents of an affected infant with an apparent sporadic case, in order to provide the couple with an accurate recurrence risk at genetic counseling.     

Congenital ocular fibrosis with musculoskeletal abnormality: a new association

Two siblings demonstrated an association of congenital ocular fibrosis (COF) syndrome with musculoskeletal abnormalities consisting of generalized muscle wasting, scoliosis, pigeon-chest deformity, bilateral fusion of the ribs in triplets, prominent coccyx, and sacral dimple. While most of the ocular and systemic "associations" hitherto described in the literature might have been coincidental, the coexistence of a generalized musculloskeletal disease with the COF syndrome raises the possibility that the ocular condition may be part of a more widespread disease process affecting the skeletal muscles.     

Vesico‐amniotic shunting for lower urinary tract obstruction in a fetus with VACTERL association

Newborn cases of VACTERL association with lower urinary tract obstruction (LUTO) are rare and there have been no reports on those patients undergoing fetal therapy in English literature. We successfully performed vesico‐amniotic shunting in a fetus having LUTO caused by abnormality of the external genitalia at 16 weeks’ gestation. Although fetal karyotype was normal 46XY, follow‐up fetal ultrasound examinations revealed ventriculomegaly in the brain, a small stomach and a right multicystic dysplastic kidney. MRI at 31 weeks’ gestation suggested lobar type holoprosencephaly. Diagnosis of VACTERL association was confirmed postnatally. We consider that vesico‐amniotic shunting is indicated for a fetus of VACTERL association with LUTO if the parents wish the procedure after genetic counseling and explanations about the fetal conditions.     

Achondrogenesis within the scope of connately manifested generalized skeletal dysplasias

4 “certain” and 2 “presumed” cases of achondrogenesis are described; 2 of them with a detailed report of patho-anatomical findings. The total of cases of so-called achondrogenesis reported in the literature up to date (more than 35 cases) has to be regarded as inhomogenous — even if cases of homozygous achondroplasia and of thanatophoric dwarfism are not included in this material. In suspected cases of achondrogenesis in future there should not be neglected especially a biochemical-histochemical differentiation of the fetal precocious manifestation of hypophosphatasia. Our cases 1 and 2 represent two types which can be differentiated within achondrogenesis itself since a long time. Histo-pathologically both types are characterized by fundamental disturbances in cartilage formation as well as by a marked disorder of osteogenesis (with the “emergency” solution of metaplastic bone formation). The attempt of a precise classification of achondrogenesis should not be made, according to our opinion, before a large series of cases from each of the currently recognized types with corresponding detailed pathological and especially biochemical documentation is available.     

Oesophageal atresia,VACTERL association: Fanconi's anaemia related spectrum of anomalies

Oesophageal atresia usually occurs without any genetic background. Three cases associated with Fanconi''s anaemia are reported. One neonate had growth retardation and numerous malformations including oesophageal atresia and four other components of the VACTERL association. In the two others, oesophageal atresia was isolated. In patients with such malformations an early diagnosis of Fanconi''s anaemia may have important genetic and therapeutic implications.

     

Identical twins concordant for pulmonary sequestration communicating with the esophagus and discordant for the VACTERL association

Communicating bronchopulmonary foregut malformations (CBPFMs) are unusual congenital structures composed of a segment of lung tissue connected to the foregut. We present what we believe is the first reported case of identical twins concordant for CBPFM who are discordant for the VACTERL association. Their nonfunctional lung tissue was successfully removed and the fistulae were corrected, and they are expected to live normal life spans. We review the literature concerning these malformations and the proposed theories of their etiology. This case report of concordance in identical twins suggests that a possible genetic component to CBPFMs cannot be ruled out. The discordance for the VACTERL association implies that the etiology is most likely multifactorial.