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.     

Diaphragmatic spinal muscular atrophy with bulbar weakness.

We present the clinical and histopathological features of a child affected by diaphragmatic spinal muscular atrophy. The child was born with mild distal arthrogryposis, mild hypotonia and developed marked diaphragmatic and bulbar muscle weakness in the first week of life. Electrophysiological and pathological investigations performed at presentation were not conclusive, while the investigations performed at 3 months showed a clear neurogenic picture. Genetic studies excluded involvement of the SMN gene, or of other genes located on chromosome 5q, confirming that this syndrome represents a different entity from typical proximal spinal muscular atrophy.     

Fatal Hepatic Short-Chain L-3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency: Clinical, Biochemical, and Pathological Studies on Three Subjects with This Recently Identified Disorder of Mitochondrial β-Oxidation

This report describes the clinical, biochemical, and pathological findings in three infants with hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) deficiency, a recently recognized disorder of the mitochondrial oxidation of straight-chain fatty acids. Candidate subjects were identified from an ongoing study of infant deaths. SCHAD analysis was performed on previously frozen liver and skeletal muscle on subjects with a characteristic urine organic acid profile. Autopsy findings were correlated with the biochemical abnormalities. Enzyme analysis in liver revealed marked deficiency in SCHAD with residual activities of 3–11%. All subjects had normal activity in skeletal muscle. However, Western blot analysis of SCHAD revealed an identical truncated protein in both liver and muscle from one patient, suggesting that SCHAD is similar in liver and muscle and that the normal activity in muscle may be due to other enzymes with C4 activity. Autopsy findings revealed marked steatosis and a muscle pattern consistent with spinal muscular atrophy in one patient. Lipid storage was less pronounced in one patient and not detected in the third patient who had a well-documented history of recurrent hypoglycemia. This is the initial pathological characterization of this enzyme defect, and our observations suggest that SCHAD deficiency is a very severe disorder contributing to early infant death. Received March 20, 1998; accepted August 7, 1998.     

Caudal regression syndrome - caudal agenesis

BACKGROUND: Neural tube defects are caused by complex genetic and environmental factors. The congenital anomaly most specific to pregnant women with diabetes mellitus is caudal regression syndrome. PATIENT: A 4-year-old boy with a history of mild delay in motor development presented with primary enuresis and encopresis. On physical examination, he had no sensory and motor deficits, but a short anal cleft. On questioning, the mother reported insulin-dependent diabetes mellitus during pregnancy. MRI of the spinal cord demonstrated a thoracic syringomyelia, a dysplastic conus medullaris, and an absence of coccyx and distal sacrum, called caudal regression syndrome or caudal agenesis. CONCLUSION: The caudal regression syndrome refers to sacral agenesis associated with spinal cord anomalies, e.g. syringomyelia. Sacral agenesis is marked by total absence of the coccyx and total or distal absence of the sacrum. An abnormal backside combined with a history of maternal diabetes mellitus in pregnancy is highly suggestive for the presence of caudal regression syndrome.     

Spinal muscular atrophy: MR evaluation

The neurogenic myopathy of spinal muscular atrophy (SMA) is degeneration of anterior horn cells of the spinal cord and associated muscle weakness. In three patients with the severe type, according to Dubowitz's classification, magnetic resonance imaging (MRI) of the lower extremity showed severe atrophy of the entire muscle bundles of the thigh and the calf. Nine intermediate type patients had ragged atrophy of muscle bundles of the thigh and the calf with selective preservation of adductor longus muscle. Five patients with the mild type had fatty infiltration of muscle bundles and increased intermuscular fat planes. MRI was insufficient for the evaluation of cervical cord abnormalities. MRI of the lower extremity was a reliable complementary modality for the diagnosis and follow-up of SMA patients.     

Complete unilateral leg duplication with ipsilateral renal agenesis

A case of a 5-month-old infant with complete duplication of the right leg and ipsilateral renal agenesis is presented. There was also a duplicated scrotum, posterior urethral valves with hydronephrosis, abnormal pelvic bones, and a ventricular septal defect. Complete caudal duplication is exceedingly rare. Associated defects are common. Several aetiological theories have been proposed. Among them, an underlying polytopic (acro-renal) developmental field defect has been suggested. It best explains the specific findings in our patient. However, the aetiology of caudal duplication syndromes may be multifactorial. In the light of twinning theories, associated duplication of hindgut derivates should be suspected in similar cases. Further research is needed. The motor-skeletal functional outcome after leg duplication surgery is mostly favourable. CONCLUSION: A case of complete unilateral leg duplication with ipsilateral renal agenesis is presented. It appears to support the theory of a polytopic developmental field defect.     

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.     

Association of Hirschsprung Disease and Bilateral Preaxial Polydactyly

Two cases with association of Hirschsprung disease and preaxial polydactyly occurring in siblings were reported. The proband was a female infant examined on the 12th day after birth. Major findings were as follows: growth retardation, mild microcephaly, rightanophthalmia, left exophthalmus associated with double disk and coloboma choroidae, ocular hypotelorism, cleft lip and palate, and bilateral preaxial polydactyly. CT scan of the brain revealed agenesis of the corpus callosum and atrophy of the cerebral cortex. Autopsy revealed alobar holoprosencephaly and agenesis of the corpus callosum, right optic nerve and olfactory nerve. Aganglionosis of the rectumwas noted at a site 10 cm from the anus. When her brother was born, bilateral preaxial polydactyly was found. He had Hirschsprung disease as well.     

Inherited motor neuron disease in domestic cats: a model of spinal muscular atrophy

Juvenile-onset spinal muscular atrophy was observed in an extended family of purebred domestic cats as a fully penetrant, simple autosomal recessive trait. Affected kittens exhibited tremor, proximal muscle weakness, and muscle atrophy beginning at ~4 mo of age. Apparent loss of function was rapid initially but progressed slowly after 7-8 mo of age, and variably disabled cats lived for at least 8 y. Electromyography and microscopic examination of muscle and nerve biopsies were consistent with denervation atrophy as a result of a central lesion. There was astrogliosis and dramatic loss of motor neurons in ventral but not dorsal horn gray matter of spinal cord and loss of axons in ventral horn nerve roots. These phenotypic findings were similar to mild forms (type III) of spinal muscular atrophy in humans caused by survival of motor neuron mutations, but molecular analysis excluded feline survival of motor neuron as the disease gene in this family. A breeding colony has been established for further investigation of this naturally occurring large-animal model of inherited motor neuron disease.     

Histopathological Study of the Biopsied Muscles from Juvenile Patients with Congenital Myotonic Dystrophy

Histopathology and histochemistry were studied in biopsied muscles from eight patients with the congenital form of myotonic dystrophy (congenital MyD) and one patient with the adult form (adult MyD). In the muscle pathology of the four patients aged between 5 and 11 years with congenital MyD, there was no immaturity of the fibers and the histological alterations were minimal. The pathological findings of the adult patient with congenital MyD resembled those of adult MyD. The immature condition of the musculature observed during the early infantile period, therefore, may once improve with motor development during childhood and, after that, the muscle fibers may degenerate in a similar manner to that seen in adult MyD. Two patients with marked talipes equinovarus displayed grouped atrophy. Small angular fibers and pyknotic nuclear clumps were observed in five patients. These findings suggest that some neurogenic factor might be involved in the muscular changes in this disorder.     

Gastroschisis with ceco-appendicular agenesis: A novel presentation

Gastroschisis is associated with intestinal atresia and malrotation. A few cases have been reported of appendicular agenesis associated with gastroschisis. No previous case has been reported of cecal agenesis with gastroschisis in the literature. As cecal agenesis is a very rare anomaly, its concomitant presentation with gastroschisis is extremely rare. We report a case of gastroschisis associated with ceco-appendicular agenesis. The possible embryological explanation for the presentation is discussed.     

Congenital colocutaneous fistula as presenting sign of prenatally closed gastroschisis

Materials and methods. An infant was born with a congenital colocutaneous fistula to the right of the base of the umbilicus, along with distal small bowel atresia. Results. These findings produced a unique presentation of a prenatally closed gastroschisis with absorption of the extruded intestine. Conclusion. This child, like all five previously reported infants with prenatally closed gastroschisis, died from complications of short-gut syndrome. Received: 1 April 1999 Accepted: 9 June 1999     

Two Cases of Fetal Akinesia/Hypokinesia Sequence

Two cases of fetal akinesia sequence are described. Both showed facial anomalies, arthrogryposis multiplex, bilateral camptodactyly, and pulmonary hypoplasia. One child had degeneration of large motor neurons of the thoracolumbosacral spinal cord and irregular atrophy of diaphragm; the other had left microphthalmia, hemiatrophy of the left temporal lobe with calcification of degenerated neurons, and hypoplasia of the cervothoracic spinal cord with decrease and degeneration of neurons. The iliopsoas and intercostal muscles showed focal myofiber atrophy. These findings suggested that some instances of this fetal akinesia syndrome might be due to neuromuscular dysfunction that occurred in utero and may have various causes.     

Two cases of fetal akinesia/hypokinesia sequence

Two cases of fetal akinesia sequence are described. Both showed facial anomalies, arthrogryposis multiplex, bilateral camptodactyly, and pulmonary hypoplasia. One child had degeneration of large motor neurons of the thoracolumbosacral spinal cord and irregular atrophy of diaphragm; the other had left microphthalmia, hemiatrophy of the left temporal lobe with calcification of degenerated neurons, and hypoplasia of the cervothoracic spinal cord with decrease and degeneration of neurons. The iliopsoas and intercostal muscles showed focal myofiber atrophy. These findings suggested that some instances of this fetal akinesia syndrome might be due to neuromuscular dysfunction that occurred in utero and may have various causes.     

THE CAT-EYE SYNDROME WITH UNUSUAL SKELETAL MALFORMATIONS

ABSTRACT. Balci, S., Halicioglu, C., Say, B. and Taysi, K. (Department of Pediatrics and Division of Clinical Genetics, Hacettepe University, Ankara, Turkey). The cat-eye syndrome with unusual skeletal malformations. Acta Paediatr Scand, 63: 623, 1974.—A fifteen day old female infant with anal atresia, rectovaginal fistula, short left forearm and agenesis of the left thumb is presented. In addition, the patient had a small, extra chromosome which was associated with D or G group chromosomes. The skeletal survey revealed aplasia of the first rib on the right as well as aplasia of the radial bone, first metacarp and thumb on the left. These radiological findings associated with the cat eye syndrome have not been reported previously.     

Mirror Movements of Hind Limbs of the Rat with Experimentally Induced Lumbosacral Agenesis

Abstract Neuropathological and electrophysiological studies were designed to clarify the pathomechanism of motor disturbance in the hind limbs of rats with sacral agenesis. The model animals were obtained from mother rats which had been treated with trypan blue on day 8 of gestation. Mirror movements in the hind limbs were observed in 7 out of 56 rats with lumbosacral agenesis. The conus medullaris in rats with lumbosacral agenesis ended at the level between Th13-L1 vertebra, whereas that in normal cases terminated between L3-4. The spinal cord of the lumbosacral region was hypoplastic and dysplastic particularly in the ventral half. Anterior horn cells were sporadic and there were no apparent median fissure in the spinal cord of the lumbosacral region. On the other hand, any abnormality was not found in the brain, the brain stem, and the spinal cord of the cervicothoracic region. Horseradish peroxidase (HRP) was injected into the unilateral hind limbs. In segments of the anomalous spinal cord, HRP-labeled neurons in the anterior horn were found not only on the injected side but also on the other side. In electrophysiological examination, F' wave was recorded on the non-stimulated side with longer latency and duration compared with that of the stimulated side. These morphological and physiological findings indicated that the mirror movements in the hind limbs of the model animals may arise from developmental errors of motor nervous pathway, with some deficient inhibitory mechanism in the upper neural system.     

Continuous muscle fiber activity syndrome

A 5.5 year old Turkish boy who suffered from progressive muscle stiffness was diagnosed as having continuous muscle fiber activity syndrome. Electromyography showed continuous motor neuron activity at rest and following intravenous injection of diazepam. Peripheral nerve block, spinal and general anesthesia diminished the spontaneous activities. The clinical and electrophysiological findings of our case were compared to the previously reported cases with emphasis on the heterogeneity of the syndrome.     

Median cleft face syndrome in association with hydrocephalus,agenesis of the corpus callosum,holoprosencephaly and choanal atresia

A premature female infant had the characteristic features of the median cleft face syndrome in association with holoprosencephaly, agenesis of the corpus callosum, hydrocephalus and choanal atresia. Whereas the nervous system is rarely affected in patients with the median cleft face syndrome, severe mental retardation has been reported in three previously published cases and is suggested in our own patient. All had an associated agenesis of the corpus callosum.Abbreviations MCF-S median cleft face syndrome - FND frontonasal dysplasia - CSF cerebrospinal fluid - ICD inner canthal distance - OCD outer canthal distance - CI canthal index - IPD inter-pupillary distance Dedicated to Prof. Dr. G. Schellong on the occasion of his 60th birthday     

Left-sided gastroschisis with caecal agenesis: A rare case report

Gastroschisis is a congenital anomaly characterised by a defect in the anterior abdominal wall through which the intestinal contents freely protrude. Defect is located almost always to right of umbilicus. To our knowledge very few cases of left-sided gastroschisis have occurred and presented in literature. We report case of left-sided gastroschisis with caecal agenesis, short gut, and malrotation of intestine.     

Paraneoplastic cerebellar degeneration and Horner syndrome: association of two uncommon findings in a child with Hodgkin disease

An 11-year-old boy admitted with a right cervical mass was found to have Hodgkin disease. On admission, he also had right Homer syndrome and severe cerebellar ataxia. Cranial MRI revealed marked cerebellar atrophy. He was treated with chemotherapy consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in addition to radiotherapy. Three months after initiation of therapy, he had a partial remission of tumor. Neurologic symptoms improved dramatically after chemotherapy started. Hodgkin disease should be included in the differential diagnosis of children with cerebellar findings and Horner syndrome.