Malformation of the Lumbosacral Spinal Cord in a Case of Sacral Agenesis

Agenesis of the sacrum is a rare anomaly that is associated with numerous visceral abnormalities, spinal cord malformation, and lower limb defects. A fatal case of sacral and lower lumbar agenesis in a 3-day-old female infant born at 38 weeks of gestation is reported. The extraneural malformations comprised an imperforate anus, a rectovaginal fistula, and musculoskeletal abnormalities, including several thoracocervical hemivertebrae and aplasia of the sacrum and the fourth and fifth lumbar vertebrae. The cervical and high thoracic spinal cord segments were normal. Disruption of secondary neurulation, possibly due to notochord dysfunction, was suggested by malformation of the ventral half of the lower thoracic spinal cord with relative preservation of the dorsal horns and, more caudally, by loss of all normal histological landmarks, including the central canal. Neither skeletal muscle nor myoblasts were found in muscle compartments that would normally have received motor innervation from the levels of the spinal cord from which anterior horn cells were absent, indicating parallel, segmental failure of myotomal differentiation in the caudal eminence.     

Arthrogryposis multiplex congenita, Pena-Shokeir phenotype, with gastroschisis and agenesis of the leg

A young mother had a stillborn infant at 33 weeks' gestation, the pregnancy complicated by polyhydramnios. The parents were unrelated, healthy, and both had a normal karyotype. The infant had multiple malformations such as ankylosis, facial anomalies, and pulmonary hypoplasia. A severe gastroschisis and agenesis of the right leg were also present. The neuropathologic findings were those of marked atrophy of anterior horn motor cells in the spinal cord and neurogenic muscle atrophy. This is a case of Pena-Shokeir syndrome with two additional features: gastroschisis and agenesis of the right leg. This syndrome represents a lethal form of arthrogryposis multiplex congenita, and the essential neuropathologic findings are marked reduction in the number of spinal motor cells and neurogenic muscle atrophy.     

Arthrogryposis Multiplex Congenita, Pena-Shokeir Phenotype, with Gastroschisis and Agenesis of the Leg

A young mother had a stillborn infant at 33 weeks' gestation, the pregnancy complicated by polyhydramnios. The parents were unrelated, healthy, and both had a normal karyotype. The infant had multiple malformations such as ankylosis, facial anomalies, and pulmonary hypoplasia. A severe gastroschisis and agenesis of the right leg were also present. The neuropathologic findings were those of marked atrophy of anterior horn motor cells in the spinal cord and neurogenic muscle atrophy. This is a case of Pena-Shokeir syndrome with two additional features: gastroschisis and agenesis of the right leg. This syndrome represents a lethal form of arthrogryposis multiplex congenita, and the essential neuropathologic findings are marked reduction in the number of spinal motor cells and neurogenic muscle atrophy.     

Microcephaly, sensorineural deafness and Currarino triad with duplication–deletion of distal 7q

Currarino syndrome (CS) is a peculiar form of caudal regression syndrome [also known as autosomal dominant sacral agenesis (OMIM no. 176450)] characterised by (1) partial absence of the sacrum with intact first sacral vertebra, (2) a pre-sacral mass and (3) anorectal anomalies (Currarino triad). We studied a 3-year-old girl with Currarino triad who had additional systemic features and performed array comparative genomic hybridisation to look for chromosomal abnormalities. This girl had the typical spectrum of anomalies of the CS including (a) partial sacral agenesis (hemisacrum with remnants of only sacral S1–S2 vertebrae and a residual S3 vertebral body) associated with complete coccygeal agenesis, (b) pre-intrasacral dermoid, (c) intra-dural lipoma, (d) ectopic anus and (e) tethered cord. She had, in addition, pre- and post-natal growth impairment (<3rd percentile), severe microcephaly (<?3 SD) with normal gyration pattern and lack of cortical thickening associated with a hypoplastic inferior vermis, facial dysmorphism, sensorineural deafness and decreased serum levels of IGF-1. A de novo 10.3-Mb duplication of 7q34–q35 and an 8.8-Mb deletion on 7q36 were identified in this patient. The Homeobox HLXB9 (CS) gene is contained within the deletion accounting for the CS phenotype including microcephaly. The spectrums of associated abnormalities in the IGF-1 deficiency growth retardation with sensorineural deafness and mental retardation syndrome (OMIM no. 608747) are discussed. To the best of our knowledge, this is the first reported case of a patient with distal 7q chromosomal imbalance and features of CS triad (including microcephaly) and the first documented case of a patient with normal gyration pattern microcephaly. The spectrum of associated anomalies in this newly recognised phenotype complex consists of growth failure, typical facial anomalies with additional (previously unreported) nervous system abnormalities (e.g. sensorineural deafness) and somatomedin C deficiency.     

Children of insulin-dependent diabetic patients. A determination of status

We report on 143 newborns of mothers with insulin dependent diabetes during pregnancy. The mean birth weight was 3.091 (+/- 619) g at a mean gestational age of 38.4 (+/- 2) weeks. Neonatal morbidity was associated with the disease class, insulin levels in the amniotic fluid, urine and cord blood; and especially persistent fetal hyperinsulinism as indicated by repeatedly high amniotic fluid insulin levels during pregnancy. One infant died (neonatal mortality 0.69%) of a severe cardiac malformation combined with a caudal regression syndrome. This was the only major malformation in the group.     

The Vater association in a newborn infant of a diabetic mother

Concerning the case history of an infant of diabetic mother, the authors analyse the possible relationship between a VATER association and a poorly controlled diabetes mellitus in the early weeks of pregnancy. Caudal regression syndrome, the most frequently observed malformation noted in infants of diabetic mothers and VATER association are the results of an "AXIAL MESODERMAL DYSPLASIA". Furthermore, the factors causing VATER association occur before the seventh week of pregnancy like those responsible for the anomalies observed in infants of diabetic mothers. It is possible that a poorly controlled diabetes mellitus before conception and in the early weeks of pregnancy could favour the appearance of VATER association.     

Caudal regression syndrome—case report and review of literature

Caudal regression syndrome is a rare disorder of distal spinal segments affecting the development of the spinal cord, with attendant sequelae. Intelligence is preserved. The exact etiology is elusive, though maternal diabetes, genetic factors, and hypoperfusion might play roles. Recently, the role of teratogens has been studied in animal models. Treatment is difficult, multidisciplinary, and largely supportive. Lower limb deformities with sensory and motor loss and neurogenic bladder call for intensive and long-term attention.     

Penis agenesis, persistent cloaca and anorectal agenesis

A case of penile agenesis with persistent cloaca and imperforate anus presents an extremely rare form of a caudal regression syndrome. Embryologic and practical considerations are discussed.     

Pancreatic agenesis as cause for neonatal diabetes mellitus

BACKGROUND: Pancreatic agenesis is a rare cause of neonatal diabetes mellitus and the knowledge about the clinical features is sparse. A patient with pancreatic agenesis and double outlet right ventricle is reported. This association has not previously been reported. In addition a synopsis of the patients (n = 14) with pancreatic agenesis who have hitherto been described is given. METHOD: We studied one patient and obtained information on 13 additional patients with pancreatic agenesis by reviewing literature. RESULTS: Literature review: In one patient the pregnancy was terminated at 19 weeks. 31 % (4/13) of the infants died in the first week and 69 % (9/13) in the first six weeks of live, 17 % (2/12) were born preterm and 83 % (10/12) at term, 93 % (13/14) had severe intrauterine growth restriction, onset of diabetes was in 6 out of 10 infants during the first two days of live, ketonuria is rare and has been reported only once. 64 % (9/14) of the infants with pancreatic agenesis had additional malformations mainly of the biliary system (50 %) and/or the heart (36 %). 31 % (4/13) of the infants survived the neonatal period and developed normally. Failure to thrive was compensated by catch-up growth after replacement of pancreatic enzymes and surgical correction of the cardiac malformation. CONCLUSIONS: Pancreatic agenesis is a clinical entity characterized by severe intrauterine growth retardation, early onset of permanent neonatal diabetes mellitus without ketoacidosis, failure to thrive due to pancreatic exocrine dysfunction and associated malformations mainly of the biliary system or of the heart. Because of the high neonatal mortality, awareness of pancreatic agenesis as a possible cause of severe intrauterine growth restriction is important for the optimal treatment of diabetes mellitus, exocrine pancreatic insufficiency and the associated malformations.     

Sirenomelia: the mermaid syndrome

Sirenomelia, or mermaid syndrome, is the extreme form of caudal regression syndrome. We present another case of this fascinating anomaly with fused lower limbs, absent external genitalia, and absent genitourinary system. The patient could not be salvaged because of bilateral renal agenesis. Detailed autopsy findings and a review of the literature are presented.     

Long-term neurological dysfunction and neonatal hypoglycaemia after diabetic pregnancy

AIM: To determine if children born to mothers with diabetes mellitus during pregnancy, who subsequently developed neonatal hypoglycaemia, experienced long-term neurological dysfunction. METHODS: Thirteen children with, and 15 without, neonatal hypoglycaemia (blood glucose < 1.5 mmol/l) were randomly selected from a larger cohort and investigated at the age of 8 years. They were also compared with 28 age matched healthy controls. RESULTS: Children with neonatal hypoglycaemia had significantly more difficulties in a validated screening test for minimal brain dysfunction than controls and were also more often reported to be hyperactive, impulsive, and easily distracted. On psychological assessment, they had a lower total development score than normoglycaemic children born to diabetic mothers, and control children. CONCLUSIONS: Neonatal hypoglycaemia in diabetic pregnancy was associated with long-term neurological dysfunction related to minimal brain dysfunction/deficits in attention, motor control, and perception.     

The Syndrome of Caudal Dysplasia: a Review, Including Etiologic Considerations and Evidence of Heterogeneity

The syndrome of caudal dysplasia (CDS) and the wide spectrum of associated skeletal and other anomalies arc reviewed, and a further case of this disorder is presented. The syndrome of CDS should be distinguished from the familial forms of sacral dysgenesis, three forms of which are tentatively identified. Two of these. usually involve some degree of “hemi-sacrum.” The third is usually manifested as partial sacral agenesis with absent distal segments. All these familial types are probably genetic dominants, and none is associated with maternal diabetes. Usually CDS is not familial, but it often is associated with a tendency toward diabetes in the mother. The suggestion is advanced here that CDS is the result of a combination of two principal factors represented by (a) a maternal diabetic tendency and (b) separate nondiabetogenic genes. Determination of the human leucocyte antigen (HLA) haplotypes involved in CDS is suggested to investigate the possibility of genetically distinctive factors in this condition.     

Infantile-onset diabetes mellitus: a 1-year follow-up study

This study evaluates the clinical profiles and outcomes of children with infantile-onset diabetes mellitus (IODM) (onset at <1 year). Twelve infants with IODM presenting to our hospital from January 2003 to December 2007 are analyzed. All undergo thorough history, clinical examination, and investigations and are managed as per hospital-approved protocol and periodically followed up. Of 12 infants (3 boys and 9 girls), 9 have a family history of DM. The median age at onset is 2.5 months. Six infants have features suggestive of Wolcott-Rallison syndrome (WRS), 4 infants have type 1 DM, and 1 infant each has Fanconi-Bickel syndrome and maturity-onset diabetes of young. None have pancreatic agenesis or calculi. Human leukocyte antigen (HLA) typing shows DQ3 and DR15 alleles predominating. Two children with WRS died; the rest are being followed up. The incidence of IODM is increasing, with multiple syndromic associations rather than a single perspective.     

Crossed fused renal ectopia with segmental fusion of bilateral ureters and abdominal aortic anomalies in a patient with caudal regression syndrome.

Caudal regression syndrome consists of multiple congenital anomalies, mainly caudal segment defects. We describe a preterm baby born to a healthy mother with typical caudal regression picture, including imperforated anus with rectovesical fistula, sacral agenesis, multiple rib and vertebral anomalies, and club feet. Crossed fused renal ectopia with fused ureters resulting in urinary obstruction was managed with transureteroureterostomy and cutaneous vesicostomy. We also found a single large umbilical artery with high abdominal aortic insertion which usually presents in sirenomelia. Because of the anatomical diversity of the urinary and cardiovascular systems associated with multiple congenital anomalies, careful evaluation is mandatory.     

Neonatal diabetes mellitus because of pancreatic agenesis with dysmorphic features and recurrent bacterial infections

Abstract:  Pancreatic agenesis is a rare cause of neonatal diabetes mellitus (NDM). It can be associated with malformations of the heart, the biliary tract, and the cerebellum. We report an infant with NDM because of pancreatic agenesis, intra-uterine growth retardation, dysmorphic features, and recurrent bacterial infections. He was born to healthy consanguineous parents. With adequate replacement of insulin and pancreatic enzymes, his blood glucose levels were controlled and his weight slowly increased. However, he continued to develop recurrent serious bacterial infections and died at the age of 11 months with sepsis and respiratory failure. Analysis of the PTF1A and PDX1 genes, which have been associated with congenital agenesis of the pancreas, did not reveal any mutation. Genetic abnormalities of chromosome 6 associated with transient neonatal diabetes as well as mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic potassium channel were also excluded as a cause of the NDM in this patient. The association of permanent neonatal diabetes because of pancreatic agenesis, dysmorphism, and non-specific immunodeficiency is previously undescribed and may represent a new possibly autosomal recessive syndrome.     

Paucity of intrahepatic bile ducts,solitary kidney and atrophic pancreas with diabetes mellitus: Atypical Alagille syndrome?

Abstract A child with the tentative diagnosis of Alagille syndrome is reported. Additional renal abnormalities are unilateral kidney agenesis and a kidney with subcortical cysts with decreased function. At the age of 5 years, insulin-dependent diabetes mellitus developed, with the pancreas being atrophic and negative pancreatic islet cell antibodies.Conclusion This observation extends the picture of Alagille syndrome and suggests an overlap with renal-hepatic-pancreatic dysplasia (Iyemark syndrome).     

HEREDITARY DEFECT OF THE SACRUM AND COCCYX WITH ANTERIOR SACRAL MENINGOCELE

Six familial cases of partial absence of the sacrum and the coccyx are described. Four had sacral ventral meningocele. There was a sex-linked dominant inheritance. The diagnosis of the meningocele was established by myelography. The symptoms were constipation and incontinence of urine. Three patients also had recurrent infections of the urinary tract, and three had congenital anal stenosis.     

Cerebro-costo-mandibular Syndrome: A New Familial Developmental Disorder

Three sibs with a hitherto unreported syndrome are described, the main features being mental handicap, palatal defects, micrognathia, and severe costovertebral defects, involving segmentation of most ribs and fusion of their dorsal ends to the vertebral bodies. In addition one infant had hypoplasia of an elbow together with defects of sacrum and coccyx; she and one other sib had minor dental defects. The syndrome is potentially lethal in the neonatal period; one of the sibs has survived. The inheritance is probably autosomal recessive.     

Diabetes mellitus in Asian Indian children and adolescents

AIM: To study the clinical and metabolic profile of type 1 and type 2 diabetes mellitus in children and adolescents in a South Asian population. RESEARCH DESIGN AND METHODS: Sixty children were recruited. They were divided into three groups: Group I--type 2 diabetes mellitus (DM2), Group II--type 1 diabetes mellitus (DM1), and Group III--healthy controls. The clinical history and biochemical parameters (HbA1c, serum insulin, C-peptide, triglycerides, total cholesterol and HDL-cholesterol) were recorded. Homeostasis model assessment for insulin resistance (HOMAIR) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS AND CONCLUSIONS: Children and adolescents with DM2 had a significant family history of DM and clinical features of insulin resistance, including increased body mass index, waist:hip ratio and acanthosis nigricans. They also had decreased insulin sensitivity together with dyslipidemia of metabolic syndrome, i.e. high triglyceride, high total cholesterol and low HDL-cholesterol. The presence of these predictors of cardiovascular disorders is known to contribute to morbidity and mortality. Hence, DM2 needs to be recognized early in Asian Indian children.     

Sacrococcygeal teratoma

Eight cases of sacrococcygeal teratoma are described. Seven patients were diagnosed at birth, and one presented at 3 1/2 months of age with urinary retention. Two patients had associated congenital anomalies (arachnoid cyst, external angular dermoid and bifid sacrum), while one had a family history of sacrococcygeal teratoma. All had the tumour removed together with the coccyx as soon as the diagnosis was made. None had recurrence of the tumour.