A concurrent occurrence of cutis laxa,Dandy-Walker syndrome and immunodeficiency in a girl

We report on a 17-y-old girl with inherited cutis laxa, immunodeficiency and Dandy-Walker syndrome. Immunodeficiency manifested itself by decreased and fluctuating levels of IgG, IgA and IgM and intermittent leucopenia causing increased susceptibility to respiratory tract infections. Dandy-Walker syndrome (agenesis of the cerebellar vermis with a large posterior fossa cyst communicating with an enlarged 4th ventricle) was shown on a CT scan but with the exception of macrocrania, no typical signs or symptoms were observed at the age of 17. Loose hyperextensible skin with pendulous skinfolds as a manifestation of cutis laxa was observed from birth. Anomalies of the right pulmonary artery, abnormal branching of the left arteria subclavia (arteria lusoria) from the left aortic arch and bicuspidal aortic valve were also present.

Conclusion: The combination of the rare disorders cutis laxa, Dandy-Walker syndrome and immunodeficiency is reported here for the first time.     

Calcinosis cutis,osteoma cutis,poikiloderma and skeletal abnormalities (COPS syndrome) — a new entity?

A 4-year-old boy with subcutaneous tumours is described. These tumours were calcified and had secondary osteoma formation. In addition the patient showed poikiloderma on the face and less prominently on arms and legs. X-ray films of the distal metaphyses of the radius, ulna and tibia revealed irregular mineralisation. Repeated laboratory tests revealed no abnormalities of fat, bone and mineral metabolism. This patient showed a unique combination of symptoms. We propose to call this syndrome: COPS-syndrome (Calcinosis cutis,Os-teoma cutis.Poikiloderma andSkeletal abnormalities).     

Spectrum of severe skeletal dysplasias in North India

Objective Severe skeletal dysplasias are a group of bone growth disorders characterized by a lethal outcome in utero or infancy. We describe our experience of the severe skeletal dysplasias diagnosed amongst fetal autopsies done at a tertiary level centre over a five year period. Methods We evaluated 15 cases with short limbed dwarfism, of which 13 fetuses were examined after termination of pregnancy and two were evaluated postnatally. Results Short rib dysplasia syndromes with or without polydactyly, osteogenesis imperfecta type II, thanatophoric dysplasia, campomelic dysplasia, chondrodysplasia punctata, rhizomelic type and achondrogenesis were the lethal skeletal dysplasias diagnosed. Conclusion Precise identification of the tye of skeletal dysplasia is paramount for proper genetic counseling. Postnatal examination and detailed radiographic examination of the fetus especially of the pelvis, limbs, skull and spine are essential to identify the type of skeletal dysplasia.     

Evaluation of newborns with skeletal dysplasias

Skeletal dysplasia are a relatively common and distinct group of genetic disorders. Even though abnormalities of bone growth are the major clinical manifestations, the pathological process may involve in any body system. Many of these disorders have dire consequences such as neonatal death and most will have life-long physical and psychosocial morbidity associated with them. Recent advances in genetic research have identified the genes underlying the primary defects in several common skeletal dysplasias such as achondroplasia and diastrophic dysplasia. While these advances are clearly important in developing better therapy and a cure for those conditions, the role of the pediatrician as the diagnostician has remained unchanged. In this article we describe how a systematic approach using the simplest of tools-clinical assessment and radiograph-can arrive at a diagnosis in most instances of newborns with skeletal dysplasias. The key features that are essential for establishing a diagnosis for most of the entities encountered in the newborn are described along with our general approach to the evaluation of the radiographs.     

Spondylothoracic dysplasia (Jarcho-Levin syndrome) in a Chinese baby

Spondylothoracic dysplasia (STD) syndrome or the Jarcho-Levin syndrome has been seen commonly in Puerto Ricans. A case of STD syndrome in a Chinese baby which we believe is the first reported case in an Asian baby is reported. The skeletal disorder syndrome affecting the spine, ribs and thorax is an autosomal recessive disorder with associated non-skeletal anomalies. It should not be confused with the phenotypically similar skeletal disorder known as spondylocostal dysplasia, which is an autosomal dominant disease.     

Biochemical,morphological and immunological findings in a patient with a cutis laxa-associated inborn disorder (De Barsy syndrome)

Clinical symptoms of a male infant are described and compared with cases now classified as the De Barsy syndrome, a distinct disorder related to cutis laxa. Morphologically, clastic fibres in skin were frayed and reduced in number and density. The collagen fibril network was normal. Biochemical studies on collagen metabolism in a skin specimen and in cultured skin fibroblasts showed a normal amino acid content and a normal electrophoretic pattern of collagen constituents. The chemotactic migration of cultured fibroblasts was diminished when compared with fibroblasts from donors of different age groups. Immunological investigations revealed an impaired granulocyte function.Abbreviations PNC polymorphonuclear cells - RBC red blood cells     

Cerebral manifestations,hemihypertrophy and lymphoedema of one leg in a child with epidermal nevus syndrome (Schimmelpenning-Feuerstein-Mims)

The report focuses on a rare variant form of epidermal nevus syndrome (ENS) (Schimmelpenning-Feuerstein-Mims syndrome) describing lesions involving the skin, eyes, skeleton, heart and brain in an 11-year-old boy. Despite his evident brain pathology, the boy lacks neurological symptoms and mental retardation. We describe his unusual MRI appearances and radiographic skeletal findings. To our knowledge this is the first report of ENS with lymphoedema occurring together in the same individual.     

Autoimmune hepatitis in a child presenting with hepatopulmonary syndrome (HPS)

HPS has been described in 9–20% of children with end‐stage liver disease. We present a case of a previously, asymptomatic nine‐yr‐old incidentally found to have low oxygen saturation. Physical exam was remarkable for digital clubbing, splenomegaly and orthodeoxia. Laboratory evaluation revealed a low platelet count, hyperammonemia, and prolonged coagulation studies. Sonography showed evidence of splenomegaly and portal venous hypertension. High resolution CT thorax and CTA were normal. HPS was confirmed by agitated saline contrast enhanced echocardiography and Tc‐99m MAA scan with evidence of intrapulmonary vascular dilatations. Liver biopsy was performed and consistent with autoimmune hepatitis. A high clinical index of suspicion should be maintained for HPS in pediatric patients who have unexplained hypoxemia as typical signs and symptoms of severe liver disease are often absent. In this report, we discuss a case of HPS complicated AIH in a pediatric patient and review the relevant literature.     

Majewski syndrome (short‐rib polydactyly syndrome type II): Prenatal diagnosis and histological features of chondral growth plate,liver and kidneys

The Majewski syndrome or short rib‐polydactyly syndrome (SRPS) type II is a lethal skeletal dysplasia characterized by severe IUGR (intrauterine growth restriction) and dysmorphic face, polydactyly, relatively proportionate head size at birth with later progression to microcephaly. A case of second trimester ultrasound diagnosis of SRPS type II is reported with review of the medical record of previous observed cases. Postmortem examination and radiogram confirmed the clinical diagnosis. Histological examination of the femoral epypheseal chondral plate showed an expanded and irregular hypertrophic zone. Moreover, characteristic cortico‐medullary cysts of both kidneys and portal fibrosis were also demonstrated; findings consistent with the broad phenotypic spectrum of this rare skeletal disease.     

"Double-muscle" trait in cattle: a possible model for Wiedemann-Beckwith syndrome

The Wiedemann-Beckwith syndrome (WBS) was first described in 1963 as a group of anomalies involving primarily macrosomia, macroglossia, and omphalocele. Histologic studies of WBS show nesidioblastosis of the pancreas, adrenocortical cytomegaly, and persistent metanephric blastema of the kidney. Multiple lines of evidence indicate that the human 11p15.5 region is the locus of abnormality in WBS. Insulin-like growth factor II (IGF-2) frequently has been considered a candidate gene, and expression of IGF-2 is known to be significantly delayed in fetal skeletal muscle of double-muscle (DM) cattle. Other candidate genes recently have been proposed for WBS. A number of recessive alleles in the bovine myostatin gene (GDF8, mapped to bovine chromosome 2 and apparently orthologous to the human 2q22 region) have been shown to be responsible for DM. Recently the first human case of deficient GDF8 function has been reported, confirming the importance of this gene. Bovine IGF-2 has been sequenced and localized to chromosome 25. The primary purpose of this study was to compare and contrast histologic findings in DM and WBS. Immunohistochemical staining confirms changes similar to nesidioblastosis in the pancreas. Other dysplastic changes of a cystic nature are seen in the adrenal. The renal histology of DM fetuses did not appear significantly different than controls.     

Congenital nephrotic syndrome of NPHS1 associated with cardiac malformation

Congenital nephrotic syndrome (CNS) is a rare disease inherited as an autosomally recessive trait and defined as proteinuria manifesting at birth or in the first 3 months of life. The classical form is the Finnish type of CNS (CNF), which is caused by mutations in the nephrin gene (NPHS1). The classical findings include prematurity, large placenta and massive proteinuria. Minor cardiac findings have been reported as a minor functional disorder but CNS with major cardiac malformation is rare. Here we report the case of a Turkish child with CNS with small indel mutation (c.614_621delCACCCCGGinsTT) in exon 6 of NPHS1 and also major cardiac malformation who did not develop end‐stage renal disease until the age of 5 years.     

Prolactin secretion abnormalities in patients with the "syndrome of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas" (Carney complex)

Carney complex is a multiple neoplasia and lentiginosis syndrome. Acromegaly due to growth hormone (GH)-producing adenomas has been considered the only pituitary-related manifestation of the complex. In the present study, seven patients with Carney complex, who belonged to three unrelated kindreds and had relatives with acromegaly, were investigated for the presence of GH and prolactin (PRL) secretion abnormalities (familial cases). In addition, four patients with the complex and no family history of the complex were studied (sporadic cases). Seven of the patients were female and four were male; their mean age was 24.27 +/- 4.34 years. Sampling every 20 min for one hour in the morning and under fasting and unstimulated conditions was performed in all patients, for determination of serum PRL levels. Insulin-like growth factor-I (IGF-I) levels and magnetic resonance imaging (MRI) of the pituitary were also obtained. Patients who had elevated IGF-I levels underwent investigation for acromegaly by oral glucose tolerance test and thyrotropin-releasing hormone. Seven of the 11 patients (63.6%) had moderately high PRL levels (mean Z score value 2.12 +/- 0.66); three of these patients also had elevated IGF-I levels but a negative investigation for acromegaly. All patients had negative pituitary MRI. The patient with the highest PRL levels underwent 24-hour sampling every 20 min, which demonstrated a higher baseline secretion of this hormone with preservation of its circadian pulsatility. Hyperprolactinemia was present in two siblings and a parent-child pair. We conclude that prolactin hypersecretion, albeit mild, appears to be frequent in patients with Carney complex, is inherited in an autosomal dominant manner in kindreds with the syndrome, and may be associated with elevated IGF-I levels in some, but not all, patients.     

Studies of malformation syndromes of man VB: The hypertelorism-hypospadias (BBB) syndrome

We describe a boy with the hypertelorism-hypospadias (BBB) syndrome. His mother and his maternal grandmother showed minor manifestations suggestive of the syndrome. The BBB syndrome is a syndrome of multiple congenital anomalies with mental retardation due a segregating mendelian mutation, either X-linked or autosomal. This paper reviews the literature on the subject and emphasizes the problem of identifying females at high risk of transmitting the condition.Supported by Grant 75/0186 from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), São Paulo, BrazilSupported by DHEW/PHS Grant GM 20 130 from the National Institute of General Medical Sciences. Paper No. 2055 from the University of Wisconsin Laboratory of Genetics     

Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.     

Facial paralysis at the age of 2 months as a first clinical sign of van Buchem disease (endosteal hyperostosis)

In this paper we report a 7.5-year-old physically normal boy with van Buchem disease (endosteal hyperostosis). Vague complaints of headache were the indication for X-ray examination. At the age of 2 months a left-side peripheral facial nerve palsy suddenly occurred in this boy. Skull X-rays gave normal results at that age suggesting that encroachment of the cranial nerves in van Buchem disease may occur as early as in the postnatal period, even before sclerosis of the skull has become radiologically visible.     

Jervell-Lange Nielsen syndrome in a family with the long QT syndrome (LQTS)

A child with Jervell-Lange Nielsen syndrome is presented from Kolkata. Family study showed that the other family members are suffering from long QT syndrome. The child had frequent syncopal attack and very prolonged QT interval requiring left cardiac sympathetic denervation and beta-blocker therapy as patient could not afford implantable defibrillator and cardiac pacing.