Profile of major congenital malformations in neonates in Al-Jahra region of Kuwait.

We investigated major congenital abnormalities in babies born in Al Jahra Hospital, Kuwait from January 2000 to December 2001. Of 7739 live and still births born over this period, 97 babies had major congenital malformations (12.5/1000 births): 49 (50.6%) babies had multiple system malformations, while 48 (49.4%) had single system anomalies. Of the 49 babies with multiple malformations, 21 (42.8%) had recognized syndromes, most of which were autosomal recessive and 17 had chromosomal aberrations. Isolated systems anomalies included central nervous system (12 cases), cardiovascular system (9 cases), skeletal system (7 cases) and gastrointestinal system (6 cases). Of the parents, 68% were consanguineous. Genetic factors were implicated in 79% of cases. Genetic services need to be provided as an effective means for the prevention of these disorders.

A morpho-etiological description of congenital limb anomalies.

BACKGROUND: Limb anomalies rank behind congenital heart disease as the most common birth defects observed in infants. More than 50 classifications for limb anomalies based on morphology and osseous anatomy have been drafted over the past 150 years. The present work aims to provide a concise summary of the most common congenital limb anomalies on a morpho-etiological basis. PATIENTS AND METHODS: In a retrospective study, 70 newborns with anomalies of the upper and/or lower limbs were ascertained through clinical examination, chromosomal analysis, skeletal surveys and other relevant investigations. RESULTS: Fetal causes of limb anomalies represented 55.8% of the cases in the form of 9 cases (12.9%) with chromosomal aberrations (trisomy 13, 18 and 21, duplication 13q and deletion 22q) and 30 cases (42.9%) with single gene disorders. An environmental etiology for limb anomalies was diagnosed in 11 cases (15.7%) as amniotic band disruption, monozygotic twin with abnormal circulation, vascular disruption (Poland sequence, sirenomelia and general vascular disruption) and an infant with a diabetic mother. Twenty cases (28.5%) had limb anomalies as part of sporadic syndromes of unknown etiology. CONCLUSIONS: The morpho-etiological work-up of limb anomalies adopted in the present study is valuable for detecting the cause of the anomaly and is crucial for its prevention. Prevention can be achieved by proper genetic counseling, which includes recurrence risk estimation and prenatal diagnosis.

Autosomal recessive nonsyndromal microcephaly with normal intelligence.

Autosomal recessive microcephaly is usually associated with moderate to severe mental retardation. An apparently new autosomal recessive disorder comprising a characteristic facial appearance associated with microcephaly and normal intelligence, immunodeficiency, and increased risk for lymphoreticular malignancies has been described recently. We report on a large Arab kindred with frequent consanguineous marriages and eight cases in five sibships with microcephaly, peculiar facies, and normal intelligence. Of these cases, two died of an acute lymphoreticular malignancy or bronchopneumonia. Immunological and chromosomal studies carried out for the three affected living sibs were normal. The existence of an autosomal recessive nonsyndromal variant of microcephaly with normal intelligence is proposed and discussed.

Nonsyndromal anencephaly: possible autosomal recessive variant.

The recurrence of anencephaly in families has been explained on a multifactorial basis. We present two unrelated families with three sibships of several nonsyndromal anencephalics including two pairs of concordantly affected like-sex twins. A rare autosomal recessive variant is proposed and inheritance is discussed in view of parental consanguinity among the two affected sibships in one family.

Apparently nonmosaic trisomy 22: clinical report and review.

We report on apparently nonmosaic trisomy 22 in a liveborn girl with multiple congenital anomalies. The abnormalities were growth retardation; microcephaly; hypertelorism; epicanthic folds; anti-mongoloid slant; apparently low-set, malformed ears; highly arched, cleft palate; short webbed neck; and hypoplastic nails. The extra 22 was found to be of maternal origin by chromosome polymorphism.

Primary hypogonadism and partial alopecia in three sibs with müllerian hypoplasia in the affected females.

We describe 3 sibs, two females and a male, with hypogonadism, defective Müllerian development in the sisters, and partial alopecia consisting of cranial hair only in the center of the scalp. One sister had absent gonads, the other had streak ovaries; both had markedly hypoplastic internal genitalia. Their brother had hormonal and histologic findings consistent with germinal cell aplasia. In view of the fact that the parents were consanguineous, autosomal recessive inheritance of the syndrome is likely.

Direct duplication of chromosome 1, dir dup(1)(p21.2----p32) in a Bedouin boy with multiple congenital anomalies.

Here we describe a Bedouin boy with a de novo duplication of 1p and multiple congenital anomalies. He had microcephaly, convergent squint, anteverted nostrils, malformed ears, micrognathia, hypoplasia of the terminal phalanges, clinodactyly of 5th fingers, simian creases, left inguinal hernia, cryptorchidism, and severe postnatal growth retardation. Our clinical findings are compared with those of previous reports of duplication involving chromosome 1p.

Late diagnosis of phenylketonuria in a Bedouin mother.

We report on the first case of phenylketonuria in a Bedouin woman with 3 children having the phenylketonuria embryofetopathy. Herein, we discuss briefly hazards of late diagnosis of maternal phenylketonuria.

Interstitial deletion of the long arm of chromosome 1 [del(1)(q32q42)].

A severely malformed girl died 7 days after birth and was found to have de novo interstitial deletion of 1q (1q32----1q42). Clinical abnormalities included microcephaly, encephalocele, small eyes with unilateral esotropia, hypertelorism but small prominent nose, highly arched palate, micrognathia, abnormal cry, apparently abnormal low-set ears, short neck with low posterior hair line, narrow shoulders, congenital heart defect, hypoplastic nails, overlap of toes with flat feet, and single umbilical artery.

A new autosomal recessive disorder resembling Weaver syndrome.

Most reported cases of Weaver syndrome are sporadic, and the mode of inheritance is still unclear. We describe two (male and female) sibs born to consanguineous Bedouin parents with manifestations resembling Weaver syndrome. Both sibs had accelerated growth of prenatal onset, hypotonia, psychomotor retardation, excess loose skin, peculiar craniofacial and acral anomalies, dental dysplasia and/or serrated gums, joint laxity, and hoarse low-pitched cry. One of them had an accelerated harmonic skeletal maturation. Differentiating features from Weaver syndrome are discussed, and autosomal recessive inheritance is suggested.

Familial uterine hernia syndrome: report of an Arab family with four affected males.

We report an Arab Bedouin family including four males with uterine hernia syndrome. All had a male chromosome constitution and phenotype, inguinal herniae, cryptochidism, and persistence of Müllerian derivatives. Histopathological studies confirmed the presence of both testicular tissue and Müllerian derivatives. The presence of two affected brothers and two affected maternal uncles suggests X-linked inheritance. Autosomal recessive determination with male sex limitation is also a possibility based on parental consanguinity in one sibship.

Greig cephalopolysyndactyly syndrome with dysgenesis of the corpus callosum in a Bedouin family.

We report on the first known Bedouin family with Greig cephalopolysyndactyly syndrome (MIM 175700). The index patient and his father shared pre- and postaxial polysyndactyly, mild mental retardation, and corpus callosum dysgenesis. Their phenotypic findings were compared with reported cases of both Greig cephalopolysyndactyly (GCPS) and acrocallosal syndromes. This family represents the second report of the rare occurrence of dysgenesis of the corpus callosum in GCPS.

Craniofacial dyssynostosis with cryptorchidism and normal stature.

We describe an Arab boy with craniofacial dyssynostosis. He presented with facial anomalies, mental retardation, epilepsy, hypotonia, and agenesis of the corpus callosum. This report reemphasises the previously reported traits of craniofacial dysostosis syndrome and suggests that cryptorchidism represents part of the syndrome profile and that the presence of normal stature does not preclude the diagnosis.

Ullrich-Turner syndrome in monozygotic twins.

We report on the Ullrich-Turner syndrome in monozygotic twin sisters. The first twin had the syndrome with a 45,X chromosome constitution. The second twin had only minor manifestations of the syndrome with 46,XX/45,X mosaicism. The literature on the Ullrich-Turner syndrome in twins is reviewed.

Kenny-Caffey syndrome in six Bedouin sibships: autosomal recessive inheritance is confirmed.

We are reporting on 16 children, in 6 unrelated sibships, born to healthy, consanguineous parents of Bedouin ancestry. Eleven of them were assessed clinically. All presented with marked growth retardation, craniofacial anomalies, small hands and feet, hypocalcemia, hypoparathyroidism, radiological evidence of cortical thickening of long bones with medullary stenosis, and absent diploic space in the skull. There was a history of 6 affected sibs dying in infancy with hypocalcemic convulsions. All cases show absence of macrocephaly and early psychomotor retardation. The present cases confirm the presence of clinical variability and co firm autosomal recessive inheritance of Kenny-Caffey syndrome.

Another Arab patient with overlap of Váradi-Papp/Opitz trigonocephaly syndromes?

We describe a Bedouin boy with multiple congenital anomalies/mental retardation (MCA/MR). He has frontal bossing, ridged metopic suture, bilateral ptosis, right squint, depressed nasal bridge, small nose, anteverted nostrils, lobulated tongue, polydactyly of both hands, microphallus, hypoplastic scrotum, microtestes, dysgenesis of corpus callosum, and a Dandy-Walker variant. This phenotype overlaps both the Varadi-Papp syndrome (OFD VI) and Opitz trigonocephaly (C syndrome). This phenotypic overlap is discussed in light of the concept of splitting and lumping in genetic diseases.

Trisomy 18 in Kuwait.

BACKGROUND: Trisomy 18 (Edwards' syndrome, T18) is the second most common trisomy in man. We describe 118 children with regular T18 who were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre during 1980-1997. METHODS: Ascertainment of T18 cases was performed shortly after birth. Chromosomal studies were carried out in addition to other relevant investigations. To investigate the factors associated with T18, a case-control study was carried out with 131 normal healthy newborns. Studied factors included maternal and paternal age, birth order, abortion, associated malformation, and survival. Multiple logistic regression analysis was used to adjust for confounding between variables. RESULTS: There was a preponderance of females among T18 cases (female:male ratio 2.1:1). The majority of T18 cases (53%) died before the second week of life. The most common associated anomalies were: congenital heart (38.1%) and gastrointestinal (25.4%). Multiplicity of malformations was also observed. Significant seasonal variation in T18 cases was detected with a peak in spring. Of the 118 T18 cases, 59 were delivered during 1994-1997 (average overall T18 birth prevalence rate 8.95 per 10 000 live births [95% CI: 6.66-11.23]). Concerning maternal age, 30.5% of the T18 cases' mothers were > or =35 years compared to 10.7% in the control group. The difference was statistically significant, P = 0.002. Logistic regression analysis showed that maternal age >30 years was a significant risk factor for T18, after adjusting for confounding with paternal age. Paternal age and abortion were not found to be significant risk factors. CONCLUSION: Trisomy 18 birth prevalence rate is high in Kuwait with advanced maternal age as a significant risk factor.

PIP: This paper describes associated factors of trisomy 18 (T18) or Edwards' syndrome among infants in Kuwait. A case control study of 131 normal newborn controls was undertaken. The study included information about gender, maternal age, paternal age, birth order, reproductive history, consanguinity, survival, and associated anomalies. Results showed a preponderance of females among T18 cases (female/male ratio, 2.1:1). The difference between the T18-case mothers and the control-group mothers was statistically significant (P = 0.002); however, there was no significant difference with regard to paternal age. The logistic regression analysis showed that the odds ratio for 2 abortions with reference to (0/1) abortion was 1.086, which is statistically significant as a risk for T18. The majority of children with T18 died before the second week of life. With regard to malformations, the most common associated anomalies were congenital heart and gastrointestinal abnormalities. Thus, the prevalence of T18 is high in Kuwait, with advanced maternal age as a significant risk factor.

Fertility with deletion Xq25: report of three cases; possible exceptions for critical region hypothesis.

We report on an Arab family in which a mother and two of her daughters, despite having deletion Xq25, are fertile. So far, only one case of deletion Xq25 associated with fertility has been reported. Consistent inactivation of the deleted X chromosome in the proposita and early menopause in the mother were noted. The effect of Xq deletion on fertility and the CRH is discussed.

Persistent Mullerian duct syndrome: report of two boys with associated crossed testicular ectopia.

Persistent Mullerian duct structures and crossed testicular ectopia were found in two phenotypically normal, unrelated males, with 46,XY karyotype, during routine herniorrhaphy. In each case, the vascular supply to the ectopic testis originated from the appropriate ipsilateral side. The clinical significance and genetic implications of this rare association are discussed.

Gerodermia osteodysplastica in a Bedouin sibship: further delineation of the syndrome.

We report a Bedouin family with gerodermia osteodysplastica in which there are two affected female siblings. They have a prematurely aged face with loose and wrinkled skin, joint laxity/dislocation, and osteoporosis. Unusual traits that have not been previously reported in association with gerodermia osteodysplastica were ear anomalies and an abnormal EEG.