OBJECTIVE: To explore the genetic basis for a child presented with renal failure and multi-cystic dysplastic kidney without anal atresia. METHODS: Peripheral blood sample of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The 40-day-old infant had presented with vomiting brown matter in a 7 days neonate and was transferred for kidney failure. Clinical examination has discovered renal failure, polycystic renal dysplasia, congenital hypothyroidism, bilateral thumb polydactyly, sensorineural hearing loss and preauricular dermatophyte. Genetic testing revealed that he has harbored a previously unreported c.824delT, p.L275Yfs*10 frameshift variant of SALL1 gene, which was confirmed by Sanger sequencing as de novo. CONCLUSION The patient was diagnosed with Townes-Brocks syndrome due to the novel de novo variant of SALL1 gene. Townes-Brocks syndrome without anal atresia is rare. Above finding has also enriched the mutational spectrum of the SALL1 gene.
Abnormalities, Multiple ; Anus, Imperforate/genetics* ; Child ; Female ; Hearing Loss, Sensorineural/genetics* ; Humans ; Infant ; Infant, Newborn ; Male ; Renal Insufficiency ; Thumb/abnormalities* ; Transcription Factors/genetics*

Prune belly syndrome is a rare congenital anomaly usually presented with triad characteristic feature of deficient abdominal muscles, cryptorchidism, and urinary tract anomalies. Here, we present a case with all the characteristic features of prune belly and the associated secondary features which were observed on detailed dissection and exploration of the fetus.
Abdominal Muscles ; Anus, Imperforate ; Cryptorchidism ; Fetus* ; Hydronephrosis ; Male ; Prune Belly Syndrome* ; Urinary Tract

Hyponatremia is defined as a plasma sodium concentration of < 135 mEq/L. It is a common electrolyte imbalance in newborns. We report the case of a term neonate with cleft lip, cleft palate, imperforate anus, normal male karyotype, and chronic hyponatremia. On the 4th day of life, he showed hyponatremia (plasma sodium concentration 130 mEq/L) with low serum osmolality (275 mOsm/kg), high urine sodium (116.7 mEq/L), and high urine osmolality (412 mOsm/kg). His thyroid and adrenal functions were normal. Despite intravenous and oral sodium supplementation and hydrocortisone treatment, hyponatremia persisted. Brain magnetic resonance imaging showed normal results. He was diagnosed as having reset osmostat, a rare subtype of the syndrome of inappropriate secretion of antidiuretic hormone characterized by a subnormal threshold for antidiuretic hormone secretion, with hypotonic hyponatremia.
Anus, Imperforate* ; Brain ; Cleft Lip* ; Cleft Palate* ; Humans ; Hydrocortisone ; Hyponatremia* ; Inappropriate ADH Syndrome ; Infant, Newborn* ; Karyotype ; Magnetic Resonance Imaging ; Male ; Osmolar Concentration ; Plasma ; Sodium ; Thyroid Gland

Neonatal hypocalcemia and congenital heart defects has been known as the first clinical manifestation of the chromosome 22q11.2 deletion syndrome (22q11DS). However, because of its wide clinical spectrum, diagnosis of 22q11DS can be delayed in children without classic symptoms. We report the case of a girl with the history of imperforate anus but without neonatal hypocalcemia or major cardiac anomaly, who was diagnosed for 22q11DS at the age of 11 after the onset of overt hypocalcemia. She was born uneventfully from phenotypically normal Korean parents. Imperforate anus and partial cleft palate were found at birth, which were surgically repaired thereafter. There was no history of neonatal hypocalcemia, and karyotyping by GTG banding was normal. At the age of 11, hypocalcemia (serum calcium, 5.0 mg/dL) and decreased parathyroid hormone level (10.8 pg/mL) was noted when she visited our Emergency Department for fever and vomiting. The 22q11DS was suspected because of her mild mental retardation and velopharyngeal insufficiency, and a microdeletion on chromosome 22q11.2 was confirmed by fluorescence in situ hybridization. The 22q11DS should be considered in the differential diagnosis of hypocalcemia at any age because of its wide clinical spectrum.
22q11 Deletion Syndrome* ; Anal Canal* ; Anus, Imperforate ; Calcium ; Child* ; Cleft Palate ; Delayed Diagnosis* ; Diagnosis ; Diagnosis, Differential ; DiGeorge Syndrome ; Emergency Service, Hospital ; Female* ; Fever ; Fluorescence ; Heart Defects, Congenital ; Humans ; Hypocalcemia* ; Hypoparathyroidism ; In Situ Hybridization ; Intellectual Disability ; Karyotyping ; Parathyroid Hormone ; Parents ; Parturition ; Velopharyngeal Insufficiency ; Vomiting

Cat eye syndrome (CES) is a very rare chromosomal syndrome characterized by various malformations such as anal atresia, preauricular malformation, coloboma of the iris, and congenial heart and renal defects. This genetic disorder is caused by partial duplication of chromosome 22, mostly as a result of a supernumerary isodicentric marker chromosome idic(22)(q11.2). Various congenital abnormalities and extreme phenotypic variability in CES patients have been reported, which have made prenatal diagnosis of CES difficult. We report the first case diagnosed with CES prenatally by multiplex ligation-dependent probe amplification in a woman who was referred to our hospital, for a fetus presenting with heart anomaly.
Animals ; Anus, Imperforate ; Cats* ; Chromosomes, Human, Pair 22* ; Coloboma ; Congenital Abnormalities ; Female ; Fetus ; Genetic Markers ; Heart ; Humans ; Iris ; Multiplex Polymerase Chain Reaction* ; Prenatal Diagnosis*

OBJECTIVETo investigate the risk factors for the development of congenital anal atresia in neonates.

METHODSA total of 70 neonates who were admitted to 17 hospitals in Foshan, China from January 2011 to December 2014 were enrolled as case group, and another 70 neonates who were hospitalized during the same period and had no anal atresia or other severe deformities were enrolled as control group. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the development of congenital anal atresia.

RESULTSThe univariate analysis revealed that the age of mothers, presence of oral administration of folic acid, infection during early pregnancy, and polyhydramnios, and sex of neonates showed significant differences between the case and control groups (P<0.05). The multivariate logistic regression analysis revealed that infection during early pregnancy (OR=18.776) and male neonates (OR=9.304) were risk factors for congenital anal atresia, and oral administration of folic acid during early pregnancy was the protective factor (OR=0.086).

CONCLUSIONSInfection during early pregnancy is the risk factor for congenital anal atresia, and male neonates are more likely to develop congenital anal atresia than female neonates. Supplementation of folic acid during early pregnancy can reduce the risk of congenital anal atresia.

Congenital anorectal malformation (ARM) is one of the most common gastrointestinal congenital diseases, accounting for 1/4 in digestive tract malformation, and is one of the congenital malformations in routine surveillance by the World Health Organization. Because of the variety of risk factors and the complexity of the pathological changes, etiology of ARM is still not clear. It is mostly considered that ARM is resulted from hereditary factors and environmental factors in the development of embryogenesis. Through animal experiments, scholars have found that Hox, Shh, Fgf, Wnt, Cdx and TCF4, Eph and ephrin play crucial role during the development of digestive tract. When the genes/signaling pathway dysfunction occurs, ARM may happen. In addition, ARM is related to the external factors in pregnancy. Because of the complexity of related factors in the development of human embryogenesis, the research progress of human ARM is very slow. This paper reviews relevant literatures in genetic factors and environmental factors, in order to provide the theoretical basis for the treatment and prevention of ARM.
Anal Canal ; abnormalities ; Anorectal Malformations ; Anus, Imperforate ; Female ; Humans ; Pregnancy ; Rectum ; abnormalities

Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by the classic triad of congenital anomalies of the anus, thumbs, and ears, with variable expressivity. Additionally, renal malformations, cardiac anomalies, and endocrine and eye abnormalities can accompany TBS, although less frequently. TBS is inherited in an autosomal dominant fashion; however, about 50% of patients have a family history of TBS and the remaining 50% have de novo mutations. SALL1, located on chromosome 16q12.1, is the only causative gene of TBS. SALL1 acts as a transcription factor and may play an important role in inducing the anomalies during embryogenesis. Clinical features of TBS overlap with those of other multiple anomaly syndromes, such as VACTERL syndrome, Baller-Gerold syndrome, Goldenhar syndrome, cat eye syndrome, and Holt-Oram syndrome. Consequently, there are some difficulties in differential diagnosis based on clinical manifestations. Herein, we report a Korean family with two generations of TBS that was diagnosed based on physical examination findings and medical history. Although the same mutation in SALL1 was identified in both the mother and the son, they displayed different clinical manifestations, suggesting a phenotypic diversity of TBS.
Anal Canal ; Animals ; Anus, Imperforate ; Cats ; Diagnosis, Differential ; Ear ; Embryonic Development ; Eye Abnormalities ; Family Characteristics ; Female ; Goldenhar Syndrome ; Hearing Loss, Sensorineural ; Humans ; Mothers ; Physical Examination ; Polydactyly ; Pregnancy ; Thumb ; Transcription Factors

OBJECTIVETo compare the clinical effect of graciloplasty using two different gracilis encircled loops and to research the better method for the treatment of fecal incontinence after anoplasty for imperforate anus.

METHODSClinical data of 38 incontinence patients with congenital anal malformation undergoing graciloplasty in our hospitals from January 2009 to January 2012 were retrospectively analyzed. Twenty patients received the modified surgery in which the gracilis muscle was transposed anticlockwise into a circum-anal tunnel with a U-loop and its tendon secured to the ipsilateral pectineal ligament. Eighteen patients received the traditional surgery in which the gracilis muscle was wrapped clockwise around the anus with a γ-loop and its tendon secured to the contralateral periosteum of ischial tuberosity or pectineal ligament. All the patients were evaluated via Wexner score and anal manometry before surgery and 2 weeks, 6 months, 1 year and 2 years after surgery. In addition, it was assessed whether the patients had difficulty defecating while squatting after surgery.

RESULTSGeneralized estimating equations showed that the Wexner score in two groups gradually decreased after surgery (P=0.000), but there was no significant difference between two groups (P=0.554). At 2 weeks, 6 months, 1 year and 2 years after surgery, there were respectively 4 cases (20.0%), 3 cases (15.0%), 2 cases (10.0%), 1 case (5.0%), who showed squatting difficult defecation in the U-loop group, and 10 cases (55.6%), 12 cases (66.7%), 10 cases (55.6%), 8 cases (44.4%) in the γ-loop group. The probability of squatting difficult defecation in U-loop group was significantly lower compared to γ-loop group (P=0.002), but the probability of squatting difficult defecation in two groups did not obviously change with time (P=0.057). Repeated measures ANOVA showed that anal resting pressure, anal maximal squeeze pressure, duration of anal squeeze, and rectal maximum tolerable volume in two groups were gradually improved after surgery (all P<0.01), but there were no significant differences between two groups (all P>0.05).

CONCLUSIONSGraciloplasty with different gracilis loops can improve anal function. However, U-loop can better improve difficult defecating while squatting, and is worthwhile for spreading in clinical practice.

Rectovestibular fistula is the most common type of anomaly found in a female newborn with anorectal malformation. However, when the baby is found to have two orifices in the introitus, rectovaginal fistula is much less common and suspected. The rare differential diagnosis of Müllerian agenesis, a condition in which the rectum shifts anteriorly and the vagina is absent, is seldom considered. In many cases, the diagnosis of Müllerian agenesis is made only during definitive anorectoplasty. In view of its impact on management, a proper examination under anaesthesia, imaging studies and a diagnostic laparoscopy may be required to confirm the presence or absence of Müllerian structures in such patients. We herein describe a patient with the rare coexistence of VACTERL association and Müllerian agenesis, and discuss the management of anorectal malformations in female patients with Müllerian agenesis.
Abnormalities, Multiple ; diagnosis ; Anal Canal ; abnormalities ; surgery ; Anorectal Malformations ; Anus, Imperforate ; complications ; diagnosis ; surgery ; Child ; Diagnosis, Differential ; Esophagus ; abnormalities ; Female ; Heart Defects, Congenital ; complications ; Humans ; Infant, Newborn ; Kidney ; abnormalities ; Laparoscopy ; Limb Deformities, Congenital ; complications ; Mullerian Ducts ; abnormalities ; Rectal Fistula ; diagnosis ; Rectum ; abnormalities ; surgery ; Spine ; abnormalities ; Trachea ; abnormalities ; Vagina ; abnormalities