Congenital short-bowel and malrotation: clinical presentation and outcome of six affected offspring in three related families.

Newborns with congenital short small bowel associated with malrotation and intestinal dysmotility have a uniformly bad prognosis. However, few long-term survivors have been reported, suggesting that the disorder is not invariably fatal. The majority of cases previously reported were familial. We report on six affected siblings in three related families. The aim of this report is to assess the mode of inheritance, the expression of this disorder, and to point to the correlation between the onset of gastrointestinal symptoms and the outcome.     

Familial juvenile polyposis coli with congenital heart disease

Seven cases of familial juvenile polyposis coli (FSPC) and one case of familial adenomatous polyposis coli (FAPC) were described in two generations of a family. Of five siblings, one had FJPC with mitral insufficiency, one had Fallot's tetralogy, and the other three, also with FJPC, had had pulmonic stenosis and died. Congenital heart disease was observed in neither the father nor the aunt. The grandfather also had FAPC, without congenital heart disease. To the best of our knowledge, this association has not previously been reported in the literature. For this paper members of the family were studied and the literature was reviewed.Presented at the 6th International Congress of Pediatric Surgery, Istanbul, 29th August – 1st September, 1989 Offprint requests to: M. Pul     

Pulmonary arteriovenous malformation in the newborn: A familial case

Summary Pulmonary arteriovenous malformation (PAVM) is a rare cause of cyanosis in the newborn with nine previously reported cases. Typical signs at presentation include cyanosis, murmur, and congestive heart failure. Abnormality on chest x-ray is common with cardiomegaly, oligemia, and focal pulmonary density. There is a male predominance, unlike older children and adults with PAVM. Familial cases of PAVM have been reported with Osler-Weber-Rendu syndrome. We report a familial case of PAVM presenting in the newborn.     

Nephronophthisis, tapeto-retinal degeneration, encephalopathy and vermian agenesis: a new association. Apropos of 3 familial cases

We observed a combination of nephronophthisis, tapetoretinal degeneration, vermian agenesis and encephalopathy in three first cousins. Juvenile nephronophthisis, the main inherited renal disease of childhood, is occasionally associated with a genetically linked disease involving the eyes and/or bone and/or liver and/or nervous system. We have assembled approximately one hundred cases of complex nephronophthisis. We discuss the various associations, among which the Senior syndrome (nephronophthisis + tapetoretinal degeneration) is the most frequent. The familial combination seen in our patients has apparently not been previously reported and seems to represent a new expression of the disease.     

Autosomal recessive omodysplasia: report of three additional cases

Three new cases of autosomal recessive omodysplasia (ARO) are reported. One shows a new finding of craniosynostosis. One is related to a patient previously reported in l991. Another is the first report of a patient living in Australia. The clinical and radiological findings further consolidate the condition as a distinct and readily diagnosable autosomal recessive bone dysplasia with marked limb shortening and facial abnormalities. These cases bring the total reported to 17. Names used in earlier publications include rhizomelic bone dysplasia with club-like femora, familial generalised micromelia with dislocated radius and congenital micromelic dysplasia (Borochowitz type). Received: 12 September 1997 Accepted: 18 September 1997     

Familial megacystis microcolon intestinal hypoperistalsis syndrome: a systematic review

Background

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and severe disorder of functional obstruction affecting bladder and bowel, usually diagnosed in the neonatal period. Over 230 cases have been reported since Berdon and colleagues first described this clinical entity in 1976. The exact pathogenesis of MMIHS is unknown. Familial occurrence of MMIHS has been reported and could offer insight into the aetiology of this disease. The purpose of this study was to systematically review the published literature for the evidence of familial MMIHS and to characterise these presentations.

Methods

A literature search was performed using the keywords “megacystis microcolon intestinal hypoperistalsis” (1976–2013). Retrieved articles, including additional studies from reference lists, were reviewed for consanguinity between parents and recurrence of MMIHS between siblings. Data were extracted for cases where familial MMIHS was present.

Results

A total of 47 patients were reported in which familial MMIHS was likely or confirmed. 15 sibling sets were definitively diagnosed with MMIHS (14 pairs and one set of three siblings). Four further index patients with a confirmed diagnosis and also one of the sibling pairs were reported to have a sibling in which MMIHS was probable. Consanguinity between parents was present in four of the confirmed sibling sets and in an additional seven individual cases. The outcome for familial MMIHS is generally poor. Multiple sibling fatalities were frequent and in only one family were both siblings’ survivors at the time of reporting.

Conclusion

Consanguinity between parents and recurrence in siblings indicate that MMIHS is inherited in an autosomal recessive manner. With the advent of next generation sequencing, these familial clusters may be key to determining the genetic basis for MMIHS.     

Hepatocellular carcinoma in Alagille's syndrome: a family study

Alagille's syndrome is a common form of familial intrahepatic cholestasis. In addition to the hepatobiliary system, many other organ systems are affected. Most of the affected patients survive through adulthood. Hepatic involvement is the cause of death in about one-third of patients. Hepatocellular carcinoma complicating the course of this disease is very rare and has been reported previously in only three cases. We report a family in which three of four siblings with this syndrome developed hepatocellular carcinoma and died as a result of it. None of these children had a liver disease, other than Alagille's syndrome, that could account for the development of such a tumor. This experience suggests that Alagille's syndrome, or at least chronic cholestasis, may be a predisposing factor for the development of hepatocellular carcinoma. Annual determination of alpha-fetoprotein and abdominal computed tomography (CT) scan may detect the development of a hepatocellular carcinoma in such cases while they are still resectable.     

Multiple Gastric Stromal Tumors in a Child without Syndromic Association Lacks Common KIT or PDGFRα Mutations

A diagnosis of multiple gastric stromal tumors that were nonmetastatic at presentation was made in an 11-year-old girl who presented with hematemesis. Gastrointestinal stromal tumor (GIST) is a rare diagnosis in childhood and reported multiple lesions are generally seen in the context of familial disease, occasionally with syndromic associations. Although there are no reports of genetic mutation in cases of pediatric GIST, very many cases of multiple GISTs investigated on a molecular level have shown germline KIT or platelet-derived growth factor receptor-α mutation; these were familial cases. Despite the negative family history in our patient, the multiplicity of lesions in such a young patient raised concern for a genetic predisposition and prompted extensive molecular workup. Repeat evaluation of distinct aliquots of tumor tissue by polymerase chain amplification followed by sequence analysis of selected coding sequences of KIT and platelet-derived growth factor receptor-α previously shown to harbor mutations in GIST, yielded no evidence of even a somatic mutation. This clinically unique case is discussed in the context of a literature review.     

Familial occurrence of bilateral renal agenesis

The 58 cases of bilateral renal agenesis (Potter syndrome) registered in the Genetic Counselling unit of our institute in the last 12 years are reviewed. The only familial recurrent case which has been prenatally diagnosed is described in detail. A urinary bladder anomaly like that of the subsequent third child has not been previously reported. The authors analyze the possible inheritance patterns. They suggest the malformation is a genetically heterogeneous entity. They emphasize that nowadays the birth of a newborn with bilateral renal agenesis can be prevented in all cases.     

Familial Occurrence of Congenital Stapes Footplate Fixation

Abstract Congenital stapes footplate fixation is not so common in the clinical otology. The clinical features are the fixation of the stapedial footplate, and the consequent conductive hearing loss with flat curve at the level of 50 to 60 dB in air conduction since birth. Its familial occurrence have never been reported before. The authors found five these cases in one family. All five cases were females, two of whom were sisters and other three were cousins. Their mothers had not particular disturbances in the early stage of pregnancy. The sex-linked heredity was highly suspected in this familial occurrence. All the cases showed bilateral conductive hearing loss. Tympanotomies on all cases revealed no abnormality of the middle ear cavity, except that all the stapes were not mobile at the footplate in spite of the normal shape. Openings of a small fenestra onto the footplate were performed and teflon piston wire prostheses were used to reconstruct the new conducting route. The excellent improvement of postoperative hearing was gained in all the cases. Furthermore, out of family members another three cases with hearing loss were found. Pathogenesis was discussed in consideration of the developmental process of the stapes and histopathological findings in the previous reports.     

Pachydermoperiostosis–critical analysis with report of five unusual cases

Pachydermoperiostosis (idiopathic hypertrophic arthropathy) {MIM 167100} is an uncommon disease characterized by unique phenotype (digital clubbing and pachydermia) and distinctive radiographic appearances (periostosis). Two families are reported that, in additional to the typical phenotype and radiographic characteristics of pachydermoperiostosis, show some rare and/or unusual, not yet reported, clinical findings. In the first family, distinctive features were severe progressive arthritis with villonodular involvement of the knees. The clinical course of the disease was much more severe than usually reported. The older brother was disabled at the age of 29 years. In the second family, the clinical history was exceptional, with unique early appearance of clinical signs. Pachydermoperiostosis is usually inherited as a dominant trait, but probable autosomal recessive inheritance has been reported. Also in the present families, autosomal recessive inheritance is likely, possibly explaining the severe clinical course of the disease. Differential diagnosis and the confusing nomenclature of pachydermoperiostosis are discussed. A. Latos-Bielenska and I. Marik are equal contributors.     

Phenotypic Variability in Two Families of Muenke Syndrome with FGFR3 Mutation

Muenke syndrome is a nonsyndromic coronal craniosynostosis, characterised by clinical and radiological variability, with occurrence of both familial and sporadic cases. Pro250Arg (P250R) is a pathogenic mutation, causing this highly clinically heterogeneous syndrome reported worldwide irrespective of race and ethnicity. The authors describe three Indian cases in two different families showing phenotypic spectrum of the disease, which was later confirmed by genetic testing.     

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.     

First report of an Asian family with hemoglobin Evans [α2 62 (E11) Val → Met]

Hemoglobin Evans is an unstable variant caused by a single nucleotide mutation that produces a valine‐to‐methionine substitution at residue 62 of the α‐globin chain. It has not been reported in the Asian population and only three cases have been reported worldwide. We diagnosed a Japanese boy with chronic hemolytic anemia with hemoglobin Evans after genetic testing. This is the first familial case of hemoglobin Evans in an Asian population.     

Persistent non-familial asymptomatic hyperphosphatasemia: a report on three cases

Three male children, aged 9 days, 2 years and 13 years, were found to have elevated serum alkaline phosphatase (ALP) activity (hyperphosphatasemia) in the absence of disease. In these three cases, elevation of ALP activity had persisted for 6-10 years. These patients did not inherit the disease from their parents. Isoenzyme determination revealed a skeletal origin of the elevated ALP in the three patients. They were diagnosed as having persistent non-familial asymptomatic hyperphosphatasemia (PNAH) which differs from transient and persistent asymptomatic familial hyperphosphatasemia. Reviewing the literature, although the term PNAH had not been used, two similar cases have been reported in a 24-year-old female and in a 27-year-old female. PNAH may be another type of benign hyperphosphatasemia.     

Intracranial desmoid tumor with familial adenomatous polyposis coli

Intracranial desmoid tumors are extremely rare. The association of desmoid tumors with familial adenomatous polyposis coli was reported previously, with the tumors involving trunk and extremities. We report a 3.5-year-old girl with intracranial desmoid tumor with familial adenomatous polyposis coli. This condition in a child is rarely reported. Follow-up of the patient after cranial surgery and of the family for this premalignant inherited condition is necessary.     

Familial extrahepatic biliary atresia

Only a small number of cases with familial extrahepatic biliary atresia, suggesting a recessive autosomal inheritance, have been reported. However, the cases reported in twins are consistent with an acquired disease. Here the case of two brothers with familial atresia of the extrahepatic biliary system is studied. Diagnosis was confirmed by laparotomy and histologic study of biliary fibrous remnants. In the present cases parental consanguinity might suggest a recessive autosomal inheritance. However, clustering of cases in a family might also suggest a common exposure to responsible factors not so far identified.     

Familial polythelia over three generations with polymastia in the youngest girl

Supernumerary nipples or polythelia are developmental abnormalities located along the embryonic mammary lines. It is the most common form of accessory breast tissue malformation and usually occurs sporadically but familial aggregation has been reported. Polythelia has been reported in association with congenital malformations, in particular with renal anomalies. Polymastia in female patients has been reported to manifest usually during pregnancy or lactation. We report on a pedigree with six cases of polythelia over three generations and one case of polythelia and polymastia in the youngest member of this family. The girl (11 years old ) had in addition to six supernumerary nipples, an accessory breast gland located under the normal left breast. No other congenital malformations could be detected. This girl will remain under follow-up until the end of puberty when the accessory breast gland will be removed. Manifestation of polymastia during puberty rarely has been reported. Conclusion Polymastia may appear with familial polythelia even without renal anomalies. Received: 16 November 2000 / Accepted: 16 January 2001     

Complete cranium bifidum without scalp abnormality. Case report

Cranium bifidum is an unusual lesion in newborns. The majority of previously reported cases have described enlarged parietal foramina with some scalp and other congenital abnormalities. In this report the authors present the first case of complete cranium bifidum without any other anomaly. The cranial defect persisted for 3 years during the follow-up period. No hereditary or familial transition has been observed. The authors conclude that such an extremely rare occurrence of complete cranium bifidum may be a result of a coincidental mutation.     

Familial Takayasu arteritis - a pediatric case and a review of the literature

Takayasu arteritis (TA) is a rare chronic inflammatory disease of the aorta and its major branches. It is seen predominantly in females during the second and third decades of life, although it can occur in childhood. The aetiology of TA remains unknown. To date, familial cases of TA have been considered rare; however, a review of the literature suggests that cases are accumulating. We report a case of two sisters affected by severe TA, and review other reported familial cases.