Two brothers with Martsolf''s syndrome.

Two brothers affected by a syndrome consisting of short stature, hypogonadism, and severe mental retardation are reported. The syndrome shares the features of that described by Martsolf et al in two brothers born to a consanguineous Polish Jewish couple. Although our patients' parents are Sephardic Jews, they deny consanguinity. These observations and personal knowledge of another affected Jewish boy raise the question of whether Martsolf's syndrome is a new entity that should be included in the group of those that affect mainly Jewish people, and whether its pattern of inheritance is X linked recessive or autosomal recessive limited to males.     

Testicular tumors in non-twin brothers from a consanguineous marriage

Malignant testicular tumors occurring in non-twin brothers are reported. Both of the brothers suffered from amentia and epilepsy and were the product of a consanguineous marriage. One brother presented with teratocarcinoma and the other seminoma. With a review of the literature, genetic roles in the etiology of testicular neoplasia are discussed.     

Cerebrofaciothoracic dysplasia: a new family.

We describe two brothers, born to consanguineous parents, who had facial dysmorphism, complex anomalies of the vertebrae and ribs, enlarged cerebral ventricles and septum pellucidum, mental retardation, and affable behaviour. The features are similar to those previously described in three unrelated children and may represent new cases of cerebrofaciothoracic dysplasia.     

TESTICULAR TUMORS IN NON-TWIN BROTHERS FROM A CONSANGUINEOUS MARRIAGE

Malignant testicular tumors occurring in non-twin brothers are reported. Both of the brothers suffered from amentia and epilepsy and were the product of a consanguineous marriage. One brother presented with teratocarcinoma and the other seminoma. With a review of the literature, genetic roles in the etiology of testicular neoplasia are discussed. ACTA PATHOL JPN 38: 1077∼1086, 1988.     

Two brothers with characteristic facial appearance,severe psychomotor retardation,hypospadias, contractures,and other symptoms: a new recessive syndrome?

We report on two severely mentally retarded male children of consanguineous parents who seem to be affected by an identical syndrome. The main physical anomalies are typical facial stigmata with a broad nasal bridge, a bulbous nose, upward slanting palpebral fissures, microretrognathia, low hair line, and large ears with an incompletely developed upper helix. In addition, both brothers had hypospadias type II, limb contractures, and delayed bone age. One child had a bilateral cleft lip with cleft palate and cryptorchidism, and developed scoliosis during adolescence. The other had bilateral inguinal hernias and strabismus. Chromosome analysis showed a normal karyotype in both. The striking similarity between the brothers, the dissimilarity to other known syndromes, and the parental consanguinity argue in favour of a new, hitherto undescribed, possibly autosomal recessive syndrome.     

Ivemark syndrome in siblings

A family in which two brothers have the lemurs syndrome is reported, thus bringing to eight the total number of families reported with multiple affected siblings. Study of 4059 autopsies, performed over 21 years at a major pediatric referral hospital, identified 32 cases of Ivemark syndrome. All were isolated occurrences in the families. One of six families which provided complete pedigree information was found to be consanguineous. This brings to four the number of reported consanguineous families with Ivemark syndrome. The male excess of affected with Ivemark syndrome is found both for the families with multiple affected siblings and for autopsy-identified cases. These data suggest a recessive inheritance of Ivemark syndrome with male predisposition.     

Autosomal recessive ectodermal dysplasia, cleft lip/palate, mental retardation, and syndactyly: the Zlotogora-Ogur syndrome

We report on 3 Brazilian brothers born to normal consanguineous parents (F = 1/16) and presenting ectodermal dysplasia, cleft lip/palate, mental retardation, syndactyly of fingers 2-3, accessory nipples, and ear anomalies. The similarities of these 3 brothers to previously reported cases and the pattern of inheritance are discussed.     

Congenital isolated leukonychia totalis in three Egyptian sibs

Isolated leukonychia totalis is a rare condition of nails with mainly an autosomal dominant pattern of inheritance. In this report, we present three sibs (a sister and two brothers) with isolated congenital leukonychia totalis, without any manifestation among parents and other family members. The sibs had similar facial features and were offspring of consanguineous Egyptian parents. We discussed possible mechanisms of inheritance and suggested an autosomal recessive mode of transmission.     

Apple peel syndrome in sibs.

We report an Arab sibship of two brothers with apple peel jejunal atresia. The parents are consanguineous. Other reported familial cases are briefly reviewed.     

Spastic paresis,glaucoma and mental retardation - a probable autosomal recessive syndrome?

A syndrome of spastic paresis, mental retardation and glaucoma has been described only once previously (Heijbel & Jagell 1981). We describe three brothers, products of a marriage between first cousins once-removed, who appear to have the same syndrome. The brothers are not dysmorphic but they have slowly progressive spastic paresis, moderate mental retardation and glaucoma with secondary cataracts. Documentation of a second consanguineous kindred with this triad of features supports the view that this is a distinct entity with an autosomal recessive mode of inheritance.     

Three sibs with achalasia and alacrimia: a separate entity different from triple-A syndrome

We report on two brothers and one sister with achalasia and alacrimia born to consanguineous unaffected parents. The combination of achalasia and alacrimia may represent an entity different from the triple-A syndrome in showing normal adrenal function.     

Newly recognized autosomal recessive faciothoracoskeletal syndrome

We report on 2 brothers, born to consanguineous parents presenting thin/long face, small ears, blepharophimosis, malar hypoplasia, long nec, pectus excavatum, brachy-camptodactyly, and sacral dimple. We suspect that these patients represent a previously undescribed autosomal recessive syndrome. © 1994 Wiley-Liss, Inc.     

Sialidosis Type 1

Observations have been made on two brothers who had progressive ataxia, intention myoclonus and visual failure starting early in the third decade of life. Their parents were consanguineous. The brothers showed bilateral cherry red spots at the maculae and bilateral perinuclear cataracts; their intelligence was preserved. Urine was found to contain large amounts of sialylated oligosaccharides; cultured skin fibroblasts showed deficiency of the enzyme sialidase (neuraminidase). Studies on leucocytes and cultured skin fibroblasts showed aberrant electrophoretic mobilities of six enzymes all of which are known to be glycoproteins, and this has been attributed to excessive amounts of sialic acid on the enzyme molecules. The clinical features together with the biochemical findings indicate that these are further cases of the newly described condition Sialidosis Type 1 and it is suggested that the electrophoretic findings might be typical of the condition.     

Anophthalmos-syndactyly (Waardenburg) syndrome without oligodactyly of toes

We report on 2 brothers from a consanguineous family from a small city of southeast Turkey. Both have bilateral anophthalmia, soft tissue syndactyly of the feet, bilateral partial synostosis of metatarsals IV and V, and basal synostosis of the fourth and fifth toes on the right in the older sib only, thus differing from all previously reported cases of anophthalmos-syndactyly syndrome. © 1995 Wiley-Liss, Inc.     

Mental retardation,premature balding,small genitalia,small acra and small patellae in brothers: Confirmation of an entity

We describe two brothers with moderate to severe mental retardation, short stature, an unusual skull shape, early anterior balding, unusual facial morphology, hypogonadotrophic hypogonadism, small genitalia, and small patellae. The older sib had generalized hypotonia without focal neurological abnormalities or myotonia. His brother had epileptic fits in infancy and tonic-clonic seizures from 5 years on, and died at 8 years of age during a seizure with possibly an intra-cerebral haemorrhage. Both brothers had a very similar face characterized by a high anterior hair line, small and upslanting palpebral fissures, deeply set eyes, a broad nasal tip, and everted lower lip. Additional studies in the older sib included a CGH array, and molecular testing of PQBP1 and FRAXA, all with normal results. Investigations of maternal lymphocytes showed completely skewed X-inactivation.The phenotype in the sibs resembles the phenotype reported in three unrelated patients reported by Scholte et al. in 1991 (MIM %181515) and Fryns et al. in 1993, and confirms this to be a clinically distinct entity. As all reported cases have been males, including two brothers, none of the parents were consanguineous, cytogenetic studies failed to show abnormalities, and X-inactivation was completely skewed in one of the mothers, we suggest this entity to follow an X-linked recessive pattern of inheritance.     

Sotos syndrome in two brothers

Two brothers presented from birth with features characteristic of Sotos syndrome (cerebral gigantism): overgrowth, craniofacial abnormalities, and mental retardation with hyperactive and aggressive behavior. X-ray examination of the hands revealed imbalanced and advanced skeletal age in one, whereas anterior fontanel bones were present in both brothers. Various hormone concentrations in plasma were all within normal limits, as were the results of a search for abnormal metabolites in plasma and urine. The occurrence of this usually sporadic syndrome in two sons of possibly remotely consanguineous, healthy parents, suggests that in some cases Sotos syndrome may be inherited as an autosomal recessive trait. Thus our observation may support the suggestion of heterogeneity of Sotos syndrome. Until specific tests for the identification of various types are available, genetic counseling for this syndrome is difficult.     

Glanzmann's thrombasthenia with mild von Willebrand's disease.

A Saudi Arabian family is reported in which Glanzmann''s thrombasthenia and von Willebrand''s disease occurred simultaneously. The daughter presented with menorrhagia and gave a history of gastrointestinal bleeding and a strong family history of bleeding disorder. Full haematological investigations were performed on the propositus, parents, and siblings, including complete blood count, bleeding time, prothrombin time, partial thromboplastin time, factor VIII:C, von Willebrand factor, ristocetin cofactor, platelet aggregometry, platelet glycoprotein Ib and IIb/IIIa and platelet antigen PLT-1 (Coulter Clone). The propositus had Glanzmann''s thrombasthenia, both parents had mild von Willebrand''s disease and were carriers of Glanzmann''s thrombasthenia. Three symptomatic brothers had both Glanzmann''s thrombasthenia and von Willebrand''s disease; two asymptomatic brothers had von Willebrand''s disease only and one had completely normal results. Those family members with both diseases were more severely affected than those with just one disease. In areas where consanguineous marriage is common, such as Saudi Arabia, multiple haemostatic abnormalities may occur, and investigation should not stop with the discovery of a single abnormality. The increased clinical severity of bleeding, including haemarthroses, in those patients having both congenital defects emphasises the importance of von Willebrand factor in glycoprotein Ib-mediated platelet adhesion.     

Oto-facio-osseous-gonadal syndrome: a new form of syndromic deafness?

In this study, we report on two brothers, born to consanguineous parents, with a syndrome of sensorineural deafness, short stature, cryptorchidism, inguinal hernia, brachycephaly, prominent forehead, flat face, downslanting palpebral fissures, low nasal root, hypoplastic alae and round tip to the nose, low-set prominent ears, narrow thorax, genu valgum, wormian bones, fusion of carpal bones, delayed bone age and congenital clubfeet. This combination of anomalies appears to be a previously undescribed syndrome, with probable autosomal recessive inheritance.     

A novel MSH2 germline mutation in homozygous state in two brothers with colorectal cancers diagnosed at the age of 11 and 12 years

Hereditary non-polyposis colorectal cancer (HNPCC) syndrome is caused by heterozygous germline mutations in DNA mismatch repair genes (MMR), (MSH2, MLH1, MSH6, and PMS2) and it is inherited in an autosomal dominant pattern with high penetrance. Several patients have been reported carrying bi-allelic MMR gene mutations and whose phenotype resembled a syndrome with childhood malignancies including hematological malignancies, brain, and colorectal tumors. This phenotype is similar to the tumor spectrum of MMR knockout mice. Herein we describe two brothers of healthy consanguineous parents from Pakistan, who had developed two and three colorectal cancers at the ages of 11 and 12 years, respectively, and less than 30 polyps. Tumor specimens were microsatellite instable (MSI-H), and expression of MSH2 and MSH6 was lost. Mutation analyses of DNA samples from both patients revealed a novel homozygous c.2006-5T > A mutation in intron 12 of the MSH2 gene. This phenotype of the brothers is unusual as they neither develop hematological malignancies nor brain tumors at an older age of presentation than other patients with homozygous MSH2 mutations. The milder phenotype may be due to the expression of low amounts of MSH2 protein with reduced activity.     

Knockout mouse models of sperm flagellum anomalies

To date, 21 knockout mouse models are known to bear specific anomalies of the sperm flagellum structures leading to motility disorders. In addition, genes responsible for flagellar defects of two well-known spontaneous mutant mice have recently been identified. These models reveal genetic factors, which are required for the proper assembly of the axoneme, the annulus, the mitochondrial sheath and the fibrous sheath. Many of these genetic factors follow unexpected cellular pathways to act on sperm flagellum morphogenesis. These mouse models may bear anomalies which are restricted to the spermatozoa or display more complex phenotypes that often include neuropathies and/or cilia-related diseases. In human, several structural disorders of the sperm flagellum found in brothers or consanguineous men probably have a genetic origin, but the genes involved have not yet been identified. The mutant mice we present in this review are invaluable models, which can be used to identify potential candidate genes for infertile men with specific sperm flagellum anomalies.