Genetics
дополнительные статьи

Genetic Center
Filatov's Child Clinical Hospital © 2001-2004
Vladimir Solonichenko MD, Clinical Geneticist,©
E-mail:

06.24.2004

	REFERENCES - FIRST PUBLICATIONS 1998	ABSTRACTS
1	al Gazali LI - Mental retardation, iris coloboma, optic atrophy and distinctive facial appearance in two sibs.Clin Dysmorphol 1998 Jul;7(3):201-3	We report an inbred Arab family from the United Arab Emirates with two children affected with mental retardation, iris coloboma, optic atrophy, nystagmus, and a distinctive facial appearance. This includes a long narrow face, downslanting palpebral fissures, a narrow nose with hypoplasia of the alae nasi, a small philtrum and a thin upper lip. We suggest that the combination of abnormalities in these children represents a previously undescribed autosomal recessive syndrome.
2	al-Gazali LI, Bakalinova D -Autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance.Clin Dysmorphol 1998 Jul;7(3):177-84	We report an inbred Omani family with four children in two sibships affected with a recessive type of multiple epiphyseal dysplasia, associated with macrocephaly frontal lobe atrophy on CT scan of the brain, lymphoedema and a distinctive facial appearance. We suggest that the constellation of abnormalities in these children represents a previously undescribed syndrome.
3	Annéren G, Meurling S, Lilja H, Wallander J, von Dobeln U. Lethal autosomal recessive syndrome with intrauterine growth retardation, intra- and extrahepatic biliary atresia, and esophageal and duodenal atresia. Am J Med Genet 1998 Jul 7;78(3):306-7 (letter)	No abstract available.
4	Balci S, Kayikcioglu A, Dagli AS. Two brothers with hypospadias, hypertelorism, upper lid coloboma and mixed type hearing loss: a new syndrome.Clin Genet 1998 Nov;54(5):440-442 (letter)	No abstract available
5	Ballo R; Beighton PH; Ramesar RS. Stickler-like *syndrome* due to a dominant negative mutation in the COL2A1 gene. Am J Med Genet, 80(1):6-11 1998 Oct 30	The type II collagenopathies include a wide spectrum of phenotypes ranging from mild spondylo epiphyseal dysplasia (SED) to severe achondrogenesis/hypochondrogenesis. Several attempts have been made at providing phenotype-genotype correlations in this group of disorders. In this report we discuss a South African family in which four members have a phenotype resembling Stickler syndrome type 1. Ocular problems and conductive deafness predominate, while skeletal changes resemble those of a mild form of multiple epiphyseal dysplasia (MED). In distinction to the classical form of Stickler syndrome, the affected persons have stubby digits. DNA analysis of the exons of the COL2A1 gene documented a C-T transversion in exon 39, resulting in an Arg704Cys substitution in the triple helical domain of the type II collagen peptide; this nontermination mutation may be indicative of further heterogeneity in the Stickler group of disorders or of a new syndrome amongst the type II collagenopathies.
6	Caridi G, Murer L, Bellantuono R, Sorino P, Caringella DA, Gusmano R, Ghiggeri GM. Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus. Am J Kidney Dis 1998 Dec;32(6):1059-62	Tapeto-retinal degeneration is frequent in patients with nephronophthisis. Association of the most severe forms of tapeto-retinal dystrophy with NPH identifies a syndrome described first by Senior et al and Loken et al. This syndrome is distinct on molecular grounds from pure renal nephronophthisis (NPH1), which has its gene locus mapped on chromosome 2q13. We describe three families with large homozygous deletion of the NPH1 locus in which mild to moderate ocular lesions due to tapeto-retinal degeneration coexisted and were correlated to renal defects. This new association of NPH1 with retinal dystrophy is characterized by focal lesions of retina and is pauci-symptomatic in clinical presentation. For this reason it may remain unrecognized in most NPH1 patients.
7	Cobeta-Garcia JC, Gascon A, Iglesias E, Estopinan V. Chondrocalcinosis and Gitelman's syndrome. A new association? Ann Rheum Dis 1998 Dec;57(12):748-9 (letter)	No abstract available.
8	Cohen MM Jr, Neri G. New overgrowth syndrome and FGFR3 dosage effect. J Med Genet 1998 Apr;35(4):348-9 (letter)	No abstract available
9	Cortes D, Thorup JM, Beck BL, Visfeldt J. Cryptorchidism as a caudal developmental field defect. A new description of cryptorchidism associated with malformations and dysplasias of the kidneys, the ureters and the spine from T10 to S5. APMIS 1998 Oct;106(10):953-8	Cryptorchidism is a feature of abnormalities in the hypothalamo-pituitary-testicular axis, and almost all disorders of sexual differentiation in which a testis is present. We found cryptorchidism to be associated with malformations and dysplasias of the kidneys, the ureters and the spine from T10 to S5. The description of this association is new. The association was seen in 18% of cryptorchid boys younger than 3 years of age in a department of paediatric surgery, in 34% of cryptorchid foetuses who died in the third trimester, in 65% of cryptorchid patients with imperforate anus, and in all individuals with tritonmelia, the male variant of sirenomelia. Sirenomelia/tritonmelia is an extreme degree of abnormal differentiation of the caudal developmental field, also called caudal dysplasia, the caudal regression syndrome and the caudal regression malformation sequence. Caudal developmental field defects were also the predominant abnormalities in the other groups of patients. Thus, cryptorchidism may be a feature of abnormal differentiation of the caudal developmental field. Position and histology of the undescended testes of the patients included in the association were similar to in cryptorchidism in general. In the literature the association was reported in 5-10% of boys considered to suffer from cryptorchidism only. Furthermore, our observations are concordant with recent theories about cryptorchidism. Consequently, we propose that cryptorchidism in general may be a caudal developmental field defect. Study of cryptorchid patients exhibiting malformations or dysplasias of the kidneys, the ureters or the spine from T10 to S5 is essential in order to isolate new genetic disorders and to spot environmental factors causing cryptorchidism.
10	Cunningham Emmett T. Jr; Dean Eliott; Neil R Miller; Irene H Maumenee; W Richard Green. Familial Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss: A possible new genetic syndrome. Arch Ophthalmol. 1998;116:78-82	Objective: To describe the clinical and ocular histopathological findings in multiple members of a family with congenital Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss. Results: Congenital Axenfeld-Rieger anomaly and glaucoma were inherited by both the proband and her male half-sibling from a phenotypically positive father and 2 different phenotypically negative mothers, suggesting an autosomal dominant inheritance. The proband's male halfsibling and her father also had atrial septal defects and sensorineural hearing loss. The proband's paternal grandmother had severe glaucoma. Histopathological analysis of blind, painful eyes removed from the proband's father and paternal grandmother showed incomplete development of the anterior chamber angle with iris stromal hypoplasia, prominent posterior embryotoxon with iris adhesions, and abnormal position and insertion of the ciliary muscles. Conclusions: This is the first description of coexisting Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss in multiple members of a single family. The iris, trabecular meshwork, and large portions of the cardiac intraventricular septum all arise from neural crest anlagen, thus supporting the notion that anterior segment dysgenesis represents a developmental disorder of the neural crest.
11	Day-Salvatore D, McLean D. Blepharophimosis, hypoplastic radius, hypoplastic left heart, telecanthus, hydronephrosis, fused metacarpals, and "prehensile" halluces: a new syndrome? Am J Med Genet 1998 Dec 4;80(4):309-13	We report on the prenatal ultrasound and postnatal findings in an infant born to a healthy, nonconsanguineous couple. The infant had microcephaly, telecanthus, blepharophimosis, cleft palate, micrognathia, abnormally modeled ears, hypoplastic left heart, hypoplastic radii and ulnae with radial subluxation, pseudoarthrotic distal humeri, fused metacarpals, tibial bowing, unusual feet with long halluces, hydronephrosis, patent urachus, abnormal electroencephalogram, and normal karyotype. To our knowledge, this combination of anomalies has not been recognized previously and may represent a new condition.
12	Duval A, Boute O, Devisme L, Valat AS, Manouvrier S. New autosomal recessive syndrome of severe microcephaly and skeletal anomalies including posterior rib-gap defects. Am J Med Genet 1998 Dec 4;80(4):429-34	We describe two female fetuses conceived by a nonconsanguineous couple. The pregnancies were interrupted at 31 and 26 weeks of gestation, respectively, because of severe microcephaly. Postmortem X-ray and autopsy studies showed in both fetuses: 1) severe intrauterine growth retardation; 2) facial anomalies characterized by severe microcephaly, sloping forehead, low set and posteriorly angulated ears, prominent eyes, down-slanting palpebral fissures, large nose, small mouth with full lips, and mild microretrognathia; 3) severe brain hypoplasia that was more pronounced in the second fetus; 4) severe rib hypoplasia with posterior rib-gap defects and in case 2 hypoplasia of several bones (right clavicle, right radius and ulna, several phalanges of hands and feet); 5) contracture at large joints. No other visceral malformations were observed, and chromosomes were normal in patient 2 and parents. This phenotype has some similarities with different syndromic entities but an identical malformation syndrome seems not to have been described previously. Autosomal recessive inheritance is the most likely cause of this putative "new syndrome."
13	Elia M, Musumeci SA, Ferri R, Scuderi C, Del Gracco S, Bottitta M, Michelucci R, Tassinari CA. Familial cortical tremor, epilepsy, and mental retardation: a distinct clinical entity? Arch Neurol 1998 Dec;55(12):1569-73	OBJECTIVE: To describe a European family with cortical tremor, epilepsy, and mental retardation, the pedigree of which indicates an autosomal dominant inheritance of the disease. DESIGN: Clinical, laboratory, neurophysiological, and neuroimaging data were studied. SETTING: Institute for research on mental retardation. PATIENTS: Two siblings (aged 25 and 28 years) and their 49-year-old mother had postural and action tremor, seizures, and mental retardation. Only tremor was present in the maternal grandmother (aged 68 years). The electroencephalogram showed diffuse spike-and-wave complexes and/or posterior spikes, and a photoparoxysmal response in the 4 subjects. The typical electrophysiologic features of cortical reflex myoclonus, such as giant somatosensory evoked potentials, enhancement of the C-reflex, and jerk-locked premyoclonus spikes, were found in all patients. CONCLUSION: This syndrome may represent a specific form of familial cortical tremor with a benign form of epilepsy and a new genetic model of cortical hyperexcitability inherited with an autosomal dominant mechanism.
14	Fryns JP, Lagae L, Rizzo WB. Pre- and postnatal growth retardation, scaling skin, moderate mental retardation and quadrispasticity, hypospadias grade 2 and hydro-uretero nephrosis, postaxial polydactyly. A distinct MCA/MR syndrome? Clin Dysmorphol 1998 Oct;7(4):275-7	We report a moderately mentally retarded 7-year-old male with a unique combination of clinical symptoms and signs: severe pre- and postnatal growth retardation, scaling skin and quadrispasticity, hypospadias grade 2 and hydro-uretero nephrosis, postaxial polydactyly type B on the right hand. Normal fibroblast enzyme activities of fatty aldehyde dehydrogenase and NADPH cytochrome C reductase were not consistent with the diagnosis of Sjogren-Larsson syndrome. The nosology of 'bird-headed' dwarfism is briefly discussed.
15	Guerrini R, Dobyns WB. Bilateral periventricular nodular heterotopia with mental retardation and frontonasal malformation. Neurology 1998 Aug;51(2):499-503	BACKGROUND AND OBJECTIVE: Bilateral periventricular nodular heterotopia (BPNH) is a recently recognized malformation of neuronal migration in which nodular masses of gray matter line the walls of the lateral ventricles. Most affected individuals are females with epilepsy and normal intelligence, but no other congenital anomalies. Studies in families with multiple affected individuals, always all females, have mapped one BPNH gene to chromosome Xq28. Several other BPNH syndromes associated with mental retardation and epilepsy but without significant dysmorphic facial features have been observed in males only, which may also be X-linked. This report describes a new syndrome with BPNH. METHODS: Clinical and MRI study and cognitive testing of two unrelated boys, aged 8 and 5.5 years, and review of the enlarging spectrum of syndromes associated with BPNH. RESULTS: Similarities between the two boys are sufficient to delineate a new multiple congenital anomaly-mental retardation syndrome that consists of BPNH, regional cortical dysplasia, mild mental retardation, and frontonasal malformation. CONCLUSIONS: The cause of this unusual syndrome is unknown; based on linkage of other BPNH syndromes to chromosome Xq28 and the report of possible X-linked inheritance of frontonasal malformation, we suspect the cause is genetic, with possible X-linked inheritance.
16	Hisama FM, Reyes-Mugica M, Wargowski DS, Thompson KJ, Mahoney MJ. Renal tubular dysgenesis, absent nipples, and multiple malformations in three brothers: a new, lethal syndrome. Am J Med Genet 1998 Dec 4;80(4):335-42	We report on three brothers with renal tubular dysgenesis and absent nipples, each also had other malformations including pre-auricular pits and a preauricular tag, branchial clefts, choanal atresia, pulmonary lobation anomaly, ventricular septal defect, type IIB interrupted aortic arch, absent gallbladder, absent thymus, parathyroid gland, accessory spleen, imperforate anus, clinodactyly, and broad digits and small nails. All three infants died neonatally. This pattern of clinical malformations appears to be a previously unreported syndrome.
17	Hopkin RJ, Cotton R, Langer LO, Saal HM. Progressive laryngotracheal stenosis with short stature and arthropathy.Am. J. Med. Genet. 80:241-246, 1998.	Laryngotracheal stenosis is rare in adults, especially in the absence of a malignancy. It is most commonly caused by fibrosis following endotracheal intubation or tracheal trauma. Other conditions causing progressive airway narrowing include the mucopolysaccharidoses and autoimmune disorders. With the exception of storage diseases, there are no well-defined genetic disorders with progressive airway narrowing as a common complication. We have evaluated three unrelated individuals with this potentially life-threatening finding, all of whom have a previously unrecognized condition. Each patient had short stature and joint stiffness with no evidence for infectious, inflammatory, or metabolic diseases as a cause of their condition. None of our patients had clinical findings indicative of known skeletal dysplasias or storage diseases. They had minor facial anomalies which included deeply set eyes, bushy eyebrows, and flat midface. Given the unique findings of our patients including adult onset critical tracheal stenosis, short stature, progressive joint limitation, and distinct facial anomalies, we conclude that they have a previously undescribed condition.
18	Inoue Y, Ono T, Kayashima K, Johno M. Hereditary perioral pigmented follicular atrophoderma associated with milia and epidermoid cysts. Br J Dermatol 1998 Oct;139(4):713-8	Eight members of a single family all presented the characteristic changes of facial, especially perioral, pigmented follicular atrophoderma, with numerous milia and epidermoid cysts. For this condition. diagnosis at a glance may be possible because of the perioral cutaneous manifestations. Histopathological examination of follicular atrophoderma revealed proliferation of basaloid cells continuous with the epidermis and coarse collagen fibres, with a decreased density of elastic fibres around the basaloid cells. Two of the eight individuals also showed generalized hypohidrosis. The eight affected persons were the proband, her son, mother, uncle, two younger sisters, cousin and nephew: an autosomal dominant mode of transmission was suggested from this family tree. The patients' symptoms resembled those of Bazex-Dupre-Christol syndrome, except for the different distribution of the follicular atrophoderma and the absence of basal cell carcinoma and hypotrichosis. This disease may be an entirely new syndrome characterized by perioral pigmented follicular atrophoderma associated with milia and epidermoid cysts.
19	Jampol M, Repetto G, Keith DA, Curtin H, Remensynder J, Holmes LB. New syndrome? Prominent, constricted ears with malformed condyle of the mandible. Am J Med Genet 1998 Feb 17;75(5):449-52	We report on several relatives in 5 generations of one family with prominence of the ears, with a marked constriction at the junction between the lower and middle thirds of the pinna. Computerized tomography and radiographs in the propositus and his affected father showed abnormalities of the condyle of the mandible. The propositus had more severe changes in the condyle with microstomia and reduced range of motion of the mandible in the temporomandibular joint. There was no hearing loss or abnormalities of the bones of the middle ear.
20	Johnson D, Horsley SW, Moloney DM, Oldridge M, Twigg SR, Walsh S, Barrow M, Njolstad PR, Kunz J, Ashworth GJ, Wall SA, Kearney L, Wilkie AO. A comprehensive screen for TWIST mutations in patients with craniosynostosis identifies a new microdeletion syndrome of chromosome band 7p21.1. Am J Hum Genet 1998 Nov;63(5):1282-93	Mutations in the coding region of the TWIST gene (encoding a basic helix-loop-helix transcription factor) have been identified in some cases of Saethre-Chotzen syndrome. Haploinsufficiency appears to be the pathogenic mechanism involved. To investigate the possibility that complete deletions of the TWIST gene also contribute to this disorder, we have developed a comprehensive strategy to screen for coding-region mutations and for complete gene deletions. Heterozygous TWIST mutations were identified in 8 of 10 patients with Saethre-Chotzen syndrome and in 2 of 43 craniosynostosis patients with no clear diagnosis. In addition to six coding-region mutations, our strategy revealed four complete TWIST deletions, only one of which associated with a translocation was suspected on the basis of conventional cytogenetic analysis. This case and two interstitial deletions were detectable by analysis of polymorphic microsatellite loci, including a novel (CA)n locus 7.9 kb away from TWIST, combined with FISH; these deletions ranged in size from 3.5 Mb to >11.6 Mb. The remaining, much smaller deletion was detected by Southern blot analysis and removed 2,924 bp, with a 2-bp orphan sequence at the breakpoint. Significant learning difficulties were present in the three patients with megabase-sized deletions, which suggests that haploinsufficiency of genes neighboring TWIST contributes to developmental delay. Our results identify a new microdeletion disorder that maps to chromosome band 7p21.1 and that causes a significant proportion of Saethre-Chotzen syndrome.
21	Kamuro K; Yoshimi S; Morikawa T. A new epileptic syndrome: ring chromosome 20-interhemispheric peak delay of spikes. No To Hattatsu, 30(5):431-2 1998 Sep (Article in Japanese)	No abstract available.
22	Kaufman LM. A syndrome of retinitis pigmentosa, congenital ichthyosis, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, and abnormal electroencephalogram. Ophthalmic Genet 1998 Jun;19(2):69-79	BACKGROUND: Retinal dystrophy and ichthyosis occur together in patients with the well-characterized disorders of Refsum disease and Sjogren-Larsson syndrome. Rud syndrome formerly was considered a genetically heterogeneous but distinct clinical entity with the manifestations of icthyosis, hypogonadism, small stature, mental retardation, epilepsy, and, infrequently, retinitis pigmentosa. Although there are at least 55 case reports of Rud syndrome in the medical literature, the existence of such a syndrome has recently been dismissed based on a new understanding of the ichthyoses. Most case reports previously reported as Rud syndrome can now be reassigned under a contemporary ichthyosis classification that does not include Rud syndrome as a distinct entity. METHODS: Two unrelated women with a disorder showing retinitis pigmentosa, congenital ichthyosis, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, and abnormal electroencephalograms underwent a comprehensive workup. The ocular and systemic findings are compared with those previously described for retinal dystrophy and ichthyosis disorders. RESULTS: These cases were found to be clearly distinct from Refsum disease, Sjogren-Larsson syndrome, and any of the other ichthyosis disorders that have been suggested as a replacement for Rud syndrome. CONCLUSION: The association of retinitis pigmentosa, congenital ichthyosis, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, and abnormal electroencephalogram may represent a distinct syndrome previously considered a subset of the now defunct Rud syndrome.
23	Kerner B, Rimoin DL, Lachman RS. Mesomelic shortening of the upper extremities with spur formation and cutaneous dimpling. Pediatr Radiol 1998 Oct;28(10):794-7	We report a boy with mesomelic dysplasia of the forearms, skin dimples, mildly bowed tibiae, metatarsus adductus, congenital cataracts, sensorineural hearing loss, hypotonia, and mildly dysmorphic features. Prominent radiologic findings include bony spurs of the diaphyses of the radii bilaterally with angulated, significantly shortened radii and ulnae and elbow dislocations. Changes in the lower extremities are confined to bowing of the tibiae and elongation of the thinned fibulae. To our knowledge this case represents a unique combination of findings not previously reported, although some resemblance was found to a patient reported by Kozlowski et al. in 1993.
24	Le Merrer M, Maroteaux P. Metaphyseal anadysplasia type II: a new regressive metaphyseal dysplasia. Pediatr Radiol 1998 Oct;28(10):771-5	We report on six unrelated children, three boys and three girls, with a metaphyseal dysplasia of early onset and spontaneous regressing evolution. During the first months of life the children present with enlargement of costochondral junctions and knobby wrists. On radiographs the metaphyseal changes of the knees are specific with fine irregularities. The femoral necks are blurred but not hypoplastic. The stature is not affected and there are no metabolic abnormalities. The radiographic findings regress during growth and the abnormalities disappear after the age of ten years. These metaphyseal changes and their mode of inheritance are different from previous cases described as anadysplasia. We propose therefore to delineate this syndrome as a new type of regressive metaphyseal dysplasia and to name it anadysplasia type II.
25	Lees MM, Hodgkins P, Reardon W, Taylor D, Stanhope R, Jones B, Hayward R, Hockley AD, Baraitser M, Winter RM. Frontonasal dysplasia with optic disc anomalies and other midline craniofacial defects: a report of six cases. Clin Dysmorphol 1998 Jul;7(3):157-62	The association of optic disc abnormalities with basal encephaloceles, specifically of the sphenoethmoidal type, and midline facial clefts has rarely been reported, although the association of midline facial clefts with encephaloceles is well described. We now report six cases of children, three males and three females, presenting with a sphenoethmoidal encephalocele, optic disc anomalies, midline facial clefting, hypertelorism, complete or partial agenesis of the corpus callosum, and endocrinological disturbances, including diabetes insipidus and pituitary dysfunction. This report underlines the importance of careful ophthalmic and endocrinological investigation of children with midline clefts associated with basal encephaloceles. These cases may represent a distinct entity within the spectrum of frontonasal dysplasia.
26	Lynch SA, Wright C, Robson SC. Bilateral renal agenesis, cardiac hypertrophy and pancytopenia, a new syndrome? Clin Dysmorphol 1998 Oct;7(4):285-8	We report a fetus with an unusual combination of features including bilateral renal agenesis, hydrops, cardiac hypertrophy and pancytopenia. There was haematological evidence of apoptosis with nuclear degeneration of megakaryocytes. The combination of structural anomalies associated with pancytopenia has many features reminiscent of Fanconi's anaemia although Mitomycin C studies were normal. There was no evidence of infection as a cause for the pancytopenia. We suggest that fetal blood sampling should be considered in similar cases with renal agenesis. Some may have a milder form of pancytopenia and may not present with hydrops thereby not prompting further haematological investigation.
27	Megarbane, A; Kharrat, K; Kreichati, G. Four sibs with dislocated elbows, bowed tibiae, scoliosis, deafness, cataract, microcephaly, and mental retardation: a new MCA/MR syndrome.JOURNAL OF MEDICAL GENETICS, 35: (9) 755-758 SEP 1998	We report four sibs with an MCA/MR syndrome whose parents were first cousins. The sibs had mental retardation, microcephaly, hearing problems, cataract, and multiple osseous malformations, such as dislocated elbows, bowed tibiae, and scoliosis. Review of published reports and the use of the London Dysmorphology Database suggest that this family presents a new syndrome.
28	MEILOF JF, V I H KWA, M. VERMEULEN, TIESSENS G. Isolated ataxia and autonomic dysfunction: a new variant of Guillain-Barré syndrome? J Neurol Neurosurg Psychiatry 1998;64:689-690 (Letter)	We report a patient with a possible new variant consisting of progressive ataxia and profound postural hypotension without appreciable weakness or sensory symptoms. We conclude that the unique combination of ataxia without loss of proprioceptive sense and severe postural hypotension as a result of autonomic neuropathy in our patient suggests either a new variant of Guillain-Barre syndrome or a new overlap syndrome of acute pandysautonomia and acute cerebellar ataxia.
29	Mortier GR, Messiaen LM, Espeel M, Smets KJ, Vanzieleghem BD, Roels F, De Paepe AM. Chondrodysplasia punctata with multiple congenital anomalies: a new syndrome? Pediatr Radiol 1998 Oct;28(10):790-3	We report a male neonate with craniofacial dysmorphic features, multiple congenital anomalies and an unusual form of chondrodysplasia punctata. Radiographic examination revealed punctate epiphyses and coronal clefting of the thoracic spine. The hand radiographs showed some similarities to the brachytelephalangic type of chondrodysplasia punctata. However, the disorder did not fit well with any known entity of chondrodysplasia punctata or other condition characterized by punctate epiphyses.
30	Mullins DA; Abel MF; Blanco JS; Fryburg JS. Familial synspondylism: progressive scoliosis and multiple hernias in a kinship. J Pediatr Orthop, 18(5):606-10 1998	A new genetic syndrome is reported of congenital lordoscoliosis due to lumbar segmentation defects and incomplete formation of lumbar vertebrae. The defect arose as a spontaneous mutation and was transmitted in an autosomal dominant fashion. The kindred included a mother and her three offspring. These affected individuals had several dysmorphic features including cavus feet and micrognathia. In addition the syndrome was associated with multiple hernias including inguinal, ventral, and diaphragmatic. These associated problems led to the early death of the first child at age 7 months. The lumbar scoliosis was already evident by that time. The progressive nature of the scoliosis was documented, especially in one child who was lost to follow-up and who was initially seen with a severe spinal deformity. Surgical management was required in members of the kindred, but because of differences in age and severity at the time of surgery, the techniques varied.
31	Nishimura G, Nakayama M, Fuke Y, Suehara N. A lethal osteochondrodysplasia with mesomelic brachymelia, round pelvis, and congenital hepatic fibrosis: two siblings born to consanguineous parents. Pediatr Radiol 1998 Jan;28(1):43-7	We report a hitherto unknown, lethal osteochondrodysplasia in two Japanese siblings born to consanguineous parents. The skeletal abnormalities are characterised by mesomelic brachymelia with bowed forearms, a round pelvis with shortened greater sciatic notches, an ossification defect of the pubic bones, and absence of ossification centers in the cervical vertebral bodies. The associated visceral anomalies comprised periportal fibrosis and cystic dysplasia of the intrahepatic bile ducts, pancreatic ductal ectasia, a simple renal cyst, microcephaly with multifocal laminar necrosis and ectopic gray matter, dysplastic tracheobronchial cartilage, abnormal lobulation of the lung, diaphragmatic hernia, and stenotic pulmonary valve. Thrombocytopenia was present but megakaryocytes were slightly increased in the bone marrow. The patients showed various dysmorphic features including aniridia, a long palpebral fissure, prominent nasal bridge, beaked nose, flat philtrum, low-set fleshy ears, micrognathia with submucosal cleft palate, and multiple joint contractures.
32	Nishimura G, Fukushima Y, Aihara T, Ohashi H, Nishimoto H, Nishimura J. Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: report of four sibs. Am J Med Genet 1998 Apr 28;77(1):1-7	We report on four Japanese sibs (three brothers and one sister) with a previously unreported syndrome of spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate, and mental retardation. Most clinical manifestations were evident neonatally, but skeletal changes and cataracts became substantial in early childhood. Radiological anomalies comprised coronal synostosis, mild epiphyseal dysplasia, particularly in the distal tibiae, strikingly delayed patellar ossification, mild metaphyseal splaying, hypoplastic ilia with iliac flare, and platyspondyly with ovoid-shaped or posteriorly humped vertebral bodies. The nonconsanguineous parents were mildly mentally retarded, and sibs of both gender were equally affected; thus, inheritance was likely autosomal recessive.
33	Nishimura G, Kurosawa K, Kobayashi H, Kawame H. Osteogenesis imperfecta-like syndrome with severe mental retardation and extrapyramidal tract signs. Pediatr Radiol 1998 Nov;28(11):856-8	We report a girl with a unique combination of malformations, including recurrent fractures, mental retardation with extrapyramidal tract signs and minor facial abnormalities. Generalised osteoporosis with overtubulation of long bones was similar to that of osteogenesis imperfecta (OI). However, the short tubular bones were distinctively undertubulated and wormian bones were not found. Based on clinical, laboratory and neuroradiological examinations, it was less likely that bone fragility was attributable to disuse bone atrophy related to her physical handicap and the neurological abnormalities secondary to brain insult. She is presumed to have a previously undescribed OI-like syndrome.
34	Nishimura G, Haga Y, Aoki K, Hasegawa T. Ischial hypoplasia, tibial hypoplasia and facial abnormalities: a new syndrome? Pediatr Radiol 1998 Dec 1;28(12):975-977	A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation of clinical and radiological findings in the present patient do not fit any known malformation syndrome.
35	Nishimura G, Tomonobu Hasegawa, Kyoko Sugii, Kaiichiro Tsuyama, Nobutake Matsuo. Joint laxity, vitreoretinal degeneration, facial abnormalities, and generalized skeletal alterations: A new syndrome? J Hum Genet., 43, 3 (1998) pp 191-194	A Japanese girl with a hitherto unknown combination of malformations is reported. The cardinal features included hyperextensibility of the joints, vitreoretinal degeneration with cataracts, and facial abnormalities, comprising hypertelorism, prominent eyes, downslanting of the palpebral fissures, mid-face recession with a short nose, deformed auricles, and microretrognathia with a high arched palate. Skeletal survey revealed multiple wormian bones, hypoplastic facial bones and mandible, narrow thorax with wavy ribs, narrow ilia, and coxa valga with slight broadening of the proximal femora, findings of which were individually minor, but the assemblage of which assisted in the syndromic identification. Although skin biopsy did not contribute to the causal clarification, it was tempting to speculate that the syndromic constellation of the present disorder resulted from an underlying defect of connective tissues.
36	Nishimura G, Toshiro Nagai. A case of craniofacial dysmorphism, congenital heart defects, coccygeal skin folds, generalized skeletal alterations, and hemihypertrophy with linear skin hypopigmentation: A new syndrome? J Hum Genet, 43, 1 (1998) pp 65-68	The case of a Japanese girl with a unique combination of congenital malformations is reported. The malformations include craniofacial dysmorphism, congenital heart defects, coccygeal skin folds, generalized skeletal alterations, and hemihypertrophy with linear skin hypopigmentation that indicated somatic mosaicism of a mutated gene or a submicroscopic chromosomal aberration. The phenotype in our patient overlapped significantly with, but was not completely consistent with, that of ter Haar syndrome, a recently elucidated malformation syndrome with an autosomal recessive trait. The present patient may have represented a previously undescribed malformation syndrome, or an atypical manifestation of ter Haar syndrome due to somatic mosaicism.
37	Njolstad PR, Reigstad H, Westby J, Espeland A. Familial non-immune hydrops fetalis and congenital pulmonary lymphangiectasia. Eur J Pediatr 1998 Jun;157(6):498-501	We report on three siblings with non-immune hydrops fetalis. Congenital pulmonary lymphangiectasia was diagnosed in two of them. One of these, a girl still alive and suffering from frequent airway infections, has bilateral pleural effusions and distal congenital lymphoedema. CONCLUSION: To our knowledge, this is the first report of non-immune hydrops fetalis and congenital pulmonary lymphangiectasia occurring in siblings.
38	Nowaczyk MJ, Hughes HE, Costa T, Clarke JT. Severe prenatal growth retardation, dysmorphic features, pigmentary retinopathy, and generalized absence of subcutaneous tissues: a new entity? Clin Dysmorphol 1998 Oct;7(4):263-8	We report a girl with severe prenatal and postnatal growth retardation, congenital generalized absence of subcutaneous tissue, and facial and somatic changes with some similarities to Wiedemann-Rautenstrauch syndrome (WRS). However, the patient's condition is sufficiently different from those reported previously to suggest that this patient represents a new syndrome. The abnormalities observed in this patient overlap with those of WRS, Cockayne syndrome, type A (CSA), and osteodysplastic primordial dwarfism type III (OPD III), but also include choanal atresia and pigmentary retinopathy.
39	Onyeije CI, Sherer DM, Handwerker S, Shah L. Prenatal diagnosis of sirenomelia with bilateral hydrocephalus: report of a previously undocumented form of VACTERL-H association. Am J Perinatol 1998 Mar;15(3):193-7	Sirenomelia represents a severe developmental field defect of the posterior axis caudal blastema, resulting in partial or complete fusion of the lower limb buds. The VATER association is a combination of morphological defects including vertebral defects, anal atresia, tracheoesophageal fistula, esophageal atresia, radial and renal anomalies. The VACTERL-H association is a rare expanded form of the VATER association that includes cardiac defects, limb defects, and hydrocephalus. It has been suggested that the VATER association may represent a less severe form of sirenomelia. In this report, we document a case in which prenatal ultrasonography detected simultaneously occurring sirenomelia and hydrocephalus. Postmortem radiography and autopsy findings confirmed the prenatal diagnosis. To our knowledge, this is the first report of prenatal diagnosis of a fetus with these two abnormalities. This report supports the hypothesis that VATER association, VACTERL-H association, and sirenomelia may represent pathophysiologically related entities.
40	O'Sullivan MJ, McAllister WH, Ball RH, Teitelbaum SL, Swanson PE, Dehner LP. Morphologic observations in a case of lethal variant (type I) metatropic dysplasia with atypical features: morphology of lethal metatropic dysplasia. Pediatr Dev Pathol 1998 Sep-Oct;1(5):405-12	Metatropic dysplasia accounts for approximately 5% of cases recorded by the International Skeletal Dysplasia Registry, with a single recorded lethal case. Four forms of the disease are currently recognized: type I, lethal autosomal recessive form; type II, nonlethal autosomal recessive form with survival to childhood; type III, autosomal dominant form with typical features, and type IV, a mild form with uncertain inheritance. The literature contains few well-documented reports of the histopathologic findings in metatropic dysplasia. In this report, we present the radiologic and histopathologic features in a cas e of type I metatropic dysplasia, with the unusual features of a persist ent tail, unique lung dysmorphology, and thyroidal agenesis.
41	Peters HL, Bankier A. Lipomatous myelomeningocele, athyrotic hypothyroidism, and sensorineural deafness: a new form of syndromal deafness? J Med Genet 1998 Nov;35(11):948-50	This case report describes a 4 year old boy with the unique triad of lipomatous myelomeningocele, congenital hypothyroidism secondary to thyroid agenesis, and sensorineural deafness. While associations between deafness and abnormal thyroid function and deafness and sacral lipoma have previously been described, the constellation of findings in this patient has not been reported.
42	Piciche M, Scanderbeg AC, Chiariello L, Levato ME, Tomai F, Pellegrino A. Atrial septal defect associated with Albright's hereditary osteodystrophy and other anomalies: a clinical case. G Ital Cardiol 1998 Sep;28(9):1012-6	A 36 year-old woman with a history of asthenia and palpitations was admitted to the Cardiac Surgery Department of Tor Vergata University, in Rome. Physical examination revealed short stature, depressed nasal bridge, hypertelorism, hypoacusia, pectus excavatum, diffuse brachydactyly, clinodactyly of the second digit of both the right hand and left foot. A 3/6 holosystolic increasing-decreasing murmur on the pulmonary focus was present at cardiac auscultation. Echocardiogram and cardiac catheterization revealed an ostium secundum atrial septal defect. X-ray examination of the hands exhibited shortening of the third, fourth and fifth metacarpals, shortening of the distal phalanges, shortening of the proximal and middle phalanges of the fifth digits and cone epiphysis of the middle phalanx of the second digits. Radiograph of the feet revealed shortening of the third and fourth and metatarsals on the left side, bilateral shortening of the first metatarsals and of the distal phalanges, cone epiphyses at the proximal base of the first toes. Additional radiographic findings included pectus excavatum and narrowing of the spinal canal. Laboratory investigations disclosed increased plasma levels of parathormone and hypocalcemia. The patient underwent primary closure of the atrial septal defect on cardiopulmonary bypass. Radiographic findings supported the diagnosis of Albright's hereditary osteodystrophy. This is a skeletal malformation involving type I-A pseudohypoparathyroidism and so-called pseudo-pseudohypoparathyroidism. Coexistence of hypocalcemia and high levels of parathormone indicated that our patient was affected with type I-A. About one-fourth of congenital heart diseases are associated with extracardiac anomalies. Although skeletal malformations appear to be the most frequent, the association of a congenital heart defect with Albright's hereditary osteodystrophy has never been described before.
43	Pierpont ME, Stewart FJ, Gorlin RJ. Plantar lipomatosis, unusual facial phenotype and developmental delay: a new MCA/MR syndrome. Am J Med Genet 1998 Jan 6;75(1):18-21	We describe two boys with global developmental delay and a phenotype of microcephaly, midface hypoplasia, enlarged fleshy ears, depressed nasal bridge, anteverted nostrils, central palatal ridge, and high forehead. Bilateral congenital fat pads are present anteromedial to the heels. Fetal finger and toe pads are present and palmar and plantar grooves are deeper than normal with "pillowing" of the areas between the grooves. No patients with similar clinical findings have been located, but these two children have a remarkably similar clinical presentation which we consider a "new" syndrome.
44	Scheffer IE, Phillips HA, O'Brien CE, Saling MM, Wrennall JA, Wallace RH, Mulley JC, Berkovic SF. Familial partial epilepsy with variable foci: a new partial epilepsy syndrome with suggestion of linkage to chromosome 2. Ann Neurol 1998 Dec;44(6):890-9	Familial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75-43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome-wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.
45	Simon David K, Michael L Rodriguez, Matthew P Frosch, Elizabeth J Quackenbush, Steven K Feske, Marvin R Natowicz. A unique familial leukodystrophy with adult onset dementia and abnormal glycolipid storage: a new lysosomal disease? J Neurol Neurosurg Psychiatry 1998;65:251-254	Two adult siblings with early onset dementia are described. At presentation, in their early 30s, they showed poor judgment and disinhibition. A progressive dementia ensued over several years. Brain MRI disclosed diffusely increased T2 signal in the cerebral white matter, suggestive of a leukodystrophy. Numerous lysosomal enzyme assays including leucocyte arylsulphatase A and galactocerebrosidase activities, plasma and fibroblast very long chain fatty acid concentrations, and urinary sulphatide concentrations were normal, as were CSF analyses. A brain biopsy disclosed periodic acid Schiff (PAS) and Sudan black positive material in perivascular macrophages which, by electron microscopy, consisted of stacks of straight or curvilinear paired membranes within angulate lysosomes, indicative of abnormal glycolipid accumulation. The combination of clinical, radiological, biochemical, and pathological features of this degenerative disease is not consistent with that of any of the known leukodystrophies or lysosomal storage disorders. These findings suggest a previously undescribed familial glycolipid storage disorder causing an adult onset leukodystrophy and presenting with behavioural symptoms that mimic a psychiatric disorder.
46	Squires LA, Dieffenbach AZ, Betz BW. Three malformation complexes related to neural crest development. Brain Dev 1998 Apr;20(3):183-5	We present an individual with three distinct malformation complexes, DiGeorge syndrome, CHARGE association and Dandy-Walker malformation. An extensive literature review has shown that DiGeorge syndrome and CHARGE association rarely occur simultaneously. The presence of both these malformation complexes with Dandy-Walker malformation has not been previously reported. These three malformation complexes may all be related by neural crest maldevelopment.
47	Temtamy SA, Meguid NA, Ismail SI, Ramzy MI. A new multiple congenital anomaly, mental retardation syndrome with preaxial brachydactyly, hyperphalangism, deafness and orodental anomalies. Clin Dysmorphol 1998 Oct;7(4):249-55	We report on a child with a 'new' syndrome characterized by multiple congential anomalies, mental retardation, sensorineural deafness, talon cusps of upper central incisors, growth retardation, bilateral symmetrical digital anomalies mainly in the form of preaxial brachydactyly and hyperphalangism of digits I-III. Because he had a similarly affected brother and his parents were cousins we suggest autosomal recessive inheritance, X-linked recessive inheritance cannot be excluded. Differential diagnosis from other syndromes with preaxial brachydactyly and hyperphalangism is presented.
48	Tsukahara M, Sugio Y. New dominant syndrome of microcephaly, facial abnormalities, micromelia, and mental retardation. J Hum Genet 1998;43(4):224-7	We report on three brothers, aged 6, 3, and 2 years, with a hitherto underscribed combination of microcephaly, facial abnormalities, micromelia, and mild mental retardation. Their facial abnormalities included a forehead with bitemporal constriction, upslanting palpebral fissures, synophrys, a short nose with anteverted nostrils, a short columella, a cupid bow-shaped, thin vermilion border of the upper lip, and micrognathia. Their mother had similar clinical manifestations, but was of normal intelligence. The disease was apparently transmitted in a dominant fashion.
49	van Asperen CJ, Overweg-Plandsoen WC, Cnossen MH, van Tijn DA, Hennekam RC. Familial neurofibromatosis type 1 associated with an overgrowth syndrome resembling Weaver syndrome. J Med Genet 1998 Apr;35(4):323-7	The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an overgrowth syndrome resembling Weaver syndrome was observed in two related cases (a mother and her son). NF1 was confirmed by molecular genetic analysis showing a large deletion at 17q11.2, encompassing the entire NF1 gene. The other symptoms in the two cases were similar to the features reported in Weaver syndrome. Although the combination of NF1 and an overgrowth syndrome resembling Weaver syndrome in this family may be fortuitous, we favour the hypothesis that the deletion of the entire gene has caused this combined phenotype. Possible pathogenetic mechanisms are discussed. The observation suggests a relation between NF1 with an extraordinarily large gene deletion and a Weaver(-like) syndrome. This warrants investigation for deletions in the 17q11.2 region in Weaver(-like) syndrome patients.
50	Van Nesselrooij BP, Spliet W, Beemer FA. Unusual association of congenital malformations: craniosynostosis, heart defect, abnormal intestinal innervation and urogenital abnormalities. Clin Dysmorphol 1998 Jan;7(1):51-3	Monozygotic male twins and an unrelated boy are described who have an unusual association of malformations, i.e. craniosynostosis of the sagittal suture, a cardiac malformation, urogenital anomalies, intestinal malformations and a single umbilical artery. The twins are discordant for these features, except for Hirschsprung disease. No similar cases could be traced in literature. The possible genetic background is discussed.
51	Watanabe T, Mochizuki H, Kohda N, Minamitani K, Minagawa M, Yasuda T, Niimi H. Autosomal dominant familial hypoparathyroidism and sensorineural deafness without renal dysplasia. Autosomal dominant familial hypoparathyroidism and sensorineural deafness without renal dysplasia. Eur.J.Endocrinology,1998,139:631-634	OBJECTIVE: A family is described which has a unique combination of autosomal dominant hypoparathyroidism and sensorineural deafness without renal dysplasia. CASE REPORT: The proband was a male infant aged 1 month with episodes of seizures for 20 days. He was born at 35 weeks' gestation without asphyxia, weighing 2040 g. His initial calcium, phosphorus and percentage of tubular reabsorption of phosphorus were 6.8 mg/dl (normal range 8.5-10.5 mg/dl), 8.9 mg/dl (normal range 5.5-7.4 mg/dl) and 96.8% (normal range 85-95%) respectively. He had normal values for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D. No abnormalities were found by renal imaging and a routine renal function study. He showed a brisk plasma cAMP increase in response to human PTH-(1-34) infusion. He had normal karyotype 46, XY, without a microdeletion in chromosome 22q11.2 by an in situ hybridization method. Five family members were affected with hypoparathyroidism with sensorineural deafness with autosomal dominant transmission. The study of calcium-sensing receptor and preproPTH gene showed a normal DNA sequence. CONCLUSION: The combination of familial hypoparathyroidism with sensorineural deafness without renal dysplasia is novel and the cause may be distinct from previously reported familial hypoparathyroidism with sensorineural deafness and renal dysplasia.
52	Weitzman JJ, Brennan LP. Bronchogastric fistula, pulmonary sequestration, malrotation of the intestine, and Meckel's diverticulum--a new association. J Pediatr Surg 1998 Nov;33(11):1655-7	Two female children, each who had a bronchogastric fistula and pulmonary sequestration (communicating bronchopulmonary foregut malformation, CBPFM) and associated malrotation of the intestine and Meckel's diverticulum are presented. Each child also presented with severe gastroesophageal reflux. The association of malrotation of the intestine and Meckel's diverticulum with a CBPFM never has been reported as a distinct entity. The concept of association of anomalies is discussed briefly.
53	Yano S, Oda K, Watanabe Y, Watanabe S, Matsuishi T, Kojima K, Abe T, Kato H. Two sib cases of Leber congenital amaurosis with cerebellar vermis hypoplasia and multiple systemic anomalies. Am J Med Genet 1998 Aug 6;78(5):429-32	Leber's congenital amaurosis (LCA), a type of congenital blindness, is clinically and genetically heterogeneous and often associated with systemic anomalies. We report on two sisters who were born to a consanguineous couple and had retinitis pigmentosa-like pigmented retinal lesions, alternating exotropia, bilateral cataracts, and anomalous coarse facies characterized by deformed skull with narrow forehead, low anterior hairline, hypertelorism, short philtrum, thin upper lip, and prominent jaw; cerebellar vermis hypoplasia; dilatation of the fourth ventricle; severe mental retardation; tremor; brisk deep tendon reflexes and abnormal behavior; and skeletal abnormalities such as limited extension of elbow and/ or finger joints and talipes equinovalgus. Skin defect and renal anomalies were seen in only one patient. Our patients are the first familial LCA associated with cerebellar vermis hypoplasia, and the disease involving particular multiple systemic anomalies may represent a distinct clinical entity.