Metabolic syndrome manifestations in an adolescent with acrodysostosis

Acrodysostosis is an extremely rare disorder characterized by short stature and peripheral dysostosis. The co-existence of metabolic syndrome and acrodysostosis in adolescence has not been previously reported in the pediatric endocrinology literature. We report a 17 year-old boy with acrodysostosis who developed metabolic syndrome, with insulin resistance and impaired glucose tolerance exhibited by an oral glucose tolerance test as well as other features of metabolic syndrome including hyperlipidemia and hypertension.     

Radiographic findings and Gs-alpha bioactivity studies and mutation screening in acrodysostosis indicate a different etiology from pseudohypoparathyroidism

Acrodysostosis is an uncommon skeletal dysplasia associated with nasal hypoplasia, midface deficiency, severe brachydactyly, and varying degrees of hearing loss and mental retardation. Previous publications have suggested that it may be difficult to distinguish acrodystostosis from pseudohypoparathyroidism on clinical grounds, but acrodysostosis does appear to have distinct clinical and radiologic findings. Spinal stenosis is an underappreciated risk in acrodysostosis, despite the reported loss of normal caudal widening of the lumbar interpediculate distance on AP spine radiographs in the original report of this disorder by Robinow et al., with confirmation of these radiographic findings by Butler et al. We report two sporadic cases of acrodysostosis, one of which required decompressive laminectomy for symptomatic spinal stenosis, and review 11 cases of acrodysostosis from 9 families that were submitted to the International Skeletal Dysplasia Registry. The objective of this report is to determine the frequency and severity of spinal stenosis in patients with acrodysostosis and to summarize the clinical and radiographic findings of acrodysostosis in an effort to distinguish acrodysostosis clearly from pseudohypoparathyroidism. The pattern of brachydactyly differs between these two conditions, and varying degrees of spinal stenosis are characteristic of acrodysostosis. Both our index patients with acrodysostosis had normal bioactivity of the alpha subunit of the Gs protein, therefore indicating that acrodysostosis has a different pathogenesis from pseudohypoparathyroidism. Furthermore, single-strand confirmational polymorphism (SSCP) analysis failed to demonstrate any confirmational alterations in the coding exons of the Gs alpha gene. These radiographic and laboratory findings substantiate that acrodysostosis is clinically different from pseudohypoparathyroidism and that it is necessary to follow patients with acrodysostosis for signs of spinal stenosis. Received: 7 June 2000 Accepted: 3 August 2000     

A boy with acromesomelic dysplasia. Growth course and growth hormone release

A 2 6/12-year-old boy is reported with the typical clinical and radiological features of acromesomelic dysplasia. This rare skeletal dysplasia is inherited as an autosomal recessive trait, and differential diagnosis is to be made with pseudoachondroplasia and acrodysostosis. Endocrine investigations were performed, and their results are found to be normal. Longitudinal growth reveals a very early slowing down of growth velocity.     

Frank -Ter Haar Syndrome in a Newborn

Frank-Ter Haar syndrome is an unusual type of skeletal dysplasia with megalocornea and developmental delay. It is usually transmitted as autosomal recessive disorder. Only a few cases have been reported in the literature and none from India. The authors report a case with other unusual features and a short review of the condition.     

Cerebro-costo-mandibular syndrome

Cerebro-costo-mandibular syndrome is a rare disorder characterized by rib malformations, various degrees of cerebral maldevelopment, mental deficiency, palatal defects, and micrognatia. This syndrome was first described in 1966. The majority of cases are sporadic, but a few instances of familial occurrence have been reported, some with an autosomal recessive pattern of inheritance. Mortality in early age has been high, probably mostly due to respiratory insufficiency secondary to rib abnormalities and flail chest. We report a mother and son with this disorder, suggesting autosomal dominant transmission. Received: 8 June 2000 Accepted: 3 August 2000     

Neu-Laxova Syndrome: Pathological Evaluation of a Fetus and Review of the Literature

Neu-Laxova syndrome is a rare autosomal recessive disorder characterized by ichthyosis, intra-uterine growth retardation, microcephaly, short neck, central nervous system abnormalities, hypo-plastic or atelectatic lungs, limb deformities, edema, polyhydramnios, and short umbilical cord. Abnormal facial features include sloping forehead, hypertelorism, severe ectropion, proptosis, malformed ears, flat nose, and micrognathia. A necropsy study of a male infant with Neu-Laxova syndrome is described. Cleft palate and ambiguous external genitalia were present in addition to anomalies characteristic of Neu-Laxova syndrome. The clinical manifestations are compared with those of the 40 previously reported cases.     

Fraser-Cryptophthalmos syndrome

Fraser or Cryptophthalmos syndrome is a variable syndrome to the extent that cryptophthalmos might not be present in all cases. However, the main features are a “hidden eye”, other craniofacial abnormalities, renal abnormalities, syndactyly and abnormal genitalia. It may be classified as isolated cryptophthalmos or cryptophthalmos sequence and cryptophthalmos syndrome. The cryptophthalmos syndrome has an autosomal recessive mode of inheritance. Isolated cryptophthalmos has been reported as an autosomal dominant trait. Prenatal diagnosis is possible using ultrasonography and fetoscopy. We report three cases of cryptophthalmos. One with renal agenesis had cryptophthalmos syndrome and the other two had isolated cryptophthalmos or cryptophthalmos sequence.     

Apert's syndrome with polymetatarsia]

Three cases of acrocephalosyndactyly with duplication of the first toe and presence of six well-individualized metatarsals are reported. This type of polysyndactyly should suggest the diagnosis of Carpenter syndrome, which is inherited on a recessive autosomal basis. However, in the three patients reported here, the facial dysmorphism was distinct from that seen in Carpenter syndrome and the syndactyly was more marked. The correct diagnosis therefore seems to be Apert acrocephalosyndactyly, a disease with dominant transmission. A mutation seems very likely and consequently the risk of recurrence in siblings is probably minimal.     

The tay syndrome (congenital ichthyosis with trichothiodystrophy)

We report a 5-year-old boy affected with the Tay syndrome, and give a review of 12 pertinent cases previously reported under various designations. The Tay syndrome is a distinct type of congenital ichthyosis characterized by a peculiar anomaly of hair growth which has been termed trichothiodystrophy. The hair shafts are extremely brittle, and they show alternating light and dark banding when examined microscopically between polarizing filters. Other features of this syndrome are low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections. The syndrome is inherited as an autosomal recessive trait. We delineate the criteria for distinguishing this gene defect from other types of congenital ichthyosis associated with disturbed hair growth, as well as from other types of trichothiodystrophy which are not associated with ichthyosis.     

Occurrence of high‐grade glioma in Noonan syndrome: Report of two cases

Noonan syndrome (NS) is an autosomal dominant disorder commonly caused by PTPN11 germline mutations. Patients are characterized by short stature, congenital heart defects, facial dysmorphism, and increased risk of malignancies including brain tumors. Commonly associated brain tumors are dysembryoplastic neuroepithelial tumor and low‐grade glioma. We report two cases of anaplastic astrocytoma with PTPN11‐related NS. We conducted a systematic search of medical databases looking for other reported cases of high‐grade glioma associated with NS and identified 24 cases of brain tumors, all of which were low‐grade glial or glioneuronal tumors except for one case of medulloblastoma.     

Bilateral Brown syndrome in three siblings.

The vast majority of cases of Brown syndrome are considered to be of a nonfamilial, sporadic nature. Documented instances of familial transmission are rare. All three siblings in one family pedigree showed bilateral Brown syndrome. Other family members were reportedly unaffected. The current cases, along with previous reports, support the concept that a subset of congenital Brown syndrome may have a strong hereditary basis, being transmitted either as an autosomal recessive genetic trait or an autosomal dominant disorder with decreased penetrance.     

Interstitial deletion of the short arm of chromosome 20 in arteriohepatic dysplasia (Alagille syndrome)

An autosomal dominant transmission of arteriohepatic dysplasia, or Alagille syndrome, with reduced penetrance and variable expressivity has been suggested from familial pedigrees, but the nature of the genetic defect and its chromosomal localization are not firmly established. We report the case of an 8-year-old boy with arteriohepatic dysplasia, in whom high-resolution chromosome study showed a partial deletion of the short arm of chromosome 20, which encompasses subbands p11.23 to p12.3. In situ hybridization and Southern blotting localized four restriction fragment length polymorphism probes within the deletion and another one distal to the deletion. Because one patient has already been reported to have arteriohepatic dysplasia and deletion of the short arm of chromosome 20, and six additional patients with such a deletion had major features of Alagille syndrome, this syndrome should now be assigned to chromosome 20p.     

Unusual dysmorphic features in five patients with Noonan's syndrome: a brief review

Noonan's syndrome is a relatively common, multiple congenital anomaly syndrome, genetically inherited as an autosomal dominant disorder with variable penetrance. It is defined by a characteristic phenotype, congenital heart disease, ocular defects and mild mental retardation. Molecular studies have confirmed that it is a heterogeneous disorder and there may be evidence for an autosomal recessive mode of inheritance.1 The gene responsible for Noonan' syndrome has been mapped to the long arm of chromosome 12.2,3 The human deltex gene (DLT x 1), mapping to chromosomal region 12q24 in the vicinity of the Noonan's syndrome critical region is being evaluated as a candidate gene for this disorder.4 Various types of musculoskeletal abnormalities have been reported, including short stature, craniofacial dysmorphism, short or webbed neck and fetal pads in fingers and toes.5 We report five cases with the unusual physical features of overriding toes and simian creases. Such abnormalities can be considered among the minor manifestations of the syndrome.     

Hypertrichosis cubiti (hairy elbow syndrome): a clue to a malformation syndrome

Hypertrichosis cubiti (HC) or hairy elbow syndrome (OMIM # 139600) consists of a localised form of long vellus hair on the extensor surfaces of the distal third of the upper arm and the proximal third of the forearm bilaterally, or occasionally on other parts of the body. In the 28 cases reported in the literature so far the elbow hair abnormality was either isolated or associated with short stature or other physical abnormalities. Most of these cases were sporadic, but autosomal dominant as well as autosomal recessive inheritance patterns have been postulated. We report on three unrelated girls (aged 7 to 11 years) of whom one presented with excess hair in the elbows alone and the other two had associated abnormalities including short stature, dysmorphic facial features and mental retardation. The literature on this subject has been reviewed and the authors focus on cases of HC with associated anomalies. A pathogenic explanation by somatic mosaicism is proposed.     

Acrodysostosis syndrome

A case of a 7-year-old boy who presented with a pontine space occupying lesion and had typical findings of acrodysostosis is presented. His 9-year-old sister and 5-year-old brother also showed similar skeletal features. His mother had short stature and a similar facial and limb features but normal radiographs, whereas the father had short stature but normal limbs and face. The pedigree of this family is suggestive of a syndrome caused by a dominant gene. The rarity of this disorder with an interesting pedigree chart prompted us to present this case and highlight the important diagnostic features and inheritance of this condition.     

Martsolf syndrome in a brother and sister: clinical features and pattern of inheritance

A brother and sister with Martsolf syndrome are reported. The main characteristics of the syndrome are mental retardation, short stature, cataracts, hypogonadism and craniofacial anomalies including microcephaly, maxillary retrusion, pouting mouth, malaligned teeth and mildly dysplastic pinnae. The metacarpal and phalangeal bones are short. The occurrence of Martsolf syndrome in sibs of opposite sex suggests autosomal recessive inheritance.Abbreviations MCPPP metacarpal phalangeal pattern profile - FSH follicle stimulating hormone - LH futeinizing hormone - TORCH toxoplasmosis, rubella, cytomegaly and herpes     

Acrodysostosis: autosomal dominant transmission

We describe a two and half year old male child with acrodysostosis, presenting with nasal hypoplasia, peripheral dysostosis (gross shortening of hands and feet), cone-shaped epiphysis, advanced bone age, and mental retardation. He and his mother also had bilateral first ray hyperplasia of the feet thereby expressing the autosomal dominant inheritance pattern.     

Association of early-onset nephrotic syndrome and microcephaly. Apropos of 4 cases in 2 families

The authors report 4 cases in 2 different families of a syndrome characterized by nephrotic syndrome of early onset (during the first 2 years of life) and microcephaly. Such an association was previously reported in 5 cases. In 4 it was familial. The study of families suggests an autosomal recessive transmission. Microcephaly was associated with psychomotor retardation, sometimes dysmorphic facies and various neurologic abnormalities. The nephrotic syndrome was characterized by its early onset and prognostic severity. However, the renal histologic lesions were heterogeneous: either minimal glomerular changes with focal and segmental hyalinosis or mesangial sclerosis, or, so-called "microcystic dysplasia". This heterogeneity does not suggest a single genetically determined disorder.     

Di George anomaly and velocardiofacial syndrome

The velocardiofacial syndrome is an autosomal dominant disorder characterized by cleft palate, cardiac anomalies, characteristic facies, and learning disabilities. The Di George anomaly involves developmental defects of the third and fourth pharyngeal pouches, resulting in thymic and parathyroid hypoplasia and cardiac defects. The cases of individuals in two families help substantiate the notion that the Di George anomaly occurs as a feature of the velocardiofacial syndrome. The proband in family 1 was a male infant with persistent hypocalcemia and cardiac defects consisting of truncus arteriosus, atrial septal defect, ventricular septal defect, and abnormal aortic arch vessels. Autopsy revealed absence of thymic and parathyroid tissue, and the Di George anomaly was diagnosed. His father had a submucous cleft palate, T cell dysfunction, and facial features consistent with the velocardiofacial syndrome. This is the third case of male-to-male transmission of velocardiofacial syndrome. The proband of family 2 was a 4-year-old girl with developmental delay, persistent neonatal hypocalcemia, ventricular septal defect, T cell dysfunction, and facial features of the velocardiofacial syndrome. The Di George anomaly has been reported to occur in at least 18 different disorders. The observation that the Di George anomaly is a component manifestation of the velocardiofacial syndrome in these two families provides further evidence that the Di George anomaly is not a distinct syndrome of a single origin but rather a heterogeneous developmental field defect. It is proposed that all previously reported cases of autosomal dominant Di George anomaly are examples of the velocardiofacial syndrome.     

Clinical and pathological aspects of ARC (arthrogryposis, renal dysfunction and cholestasis) syndrome in two siblings

We describe the first family report of ARC syndrome (arthrogryposis multiplex congenita, renal dysfunction, and cholestasis) diagnosed in Turkey. ARC syndrome is a rare cause of cholestatic jaundice and skeletal abnormalities in the neonatal period. Fanconi-like renal tubular dysfunction completed the clinical picture. Consanguinity and affected membership are the other typical components of this rare disorder, and possibility of autosomal recessive transmission was considered. A broad spectrum of histopathological abnormalities have been described in the liver and kidney. In this report, we describe two male siblings with ARC syndrome who had cholestatic jaundice, arthrogryposis multiplex congenital-like joint contractures and renal involvement with additional clinical features. Clinical and pathological aspects of the syndrome are discussed and compared with the other cases in the literature.