Increased need for medical interventions in infants with velocardiofacial (deletion 22q11) syndrome.

Ten of 12 patients diagnosed with deletion 22q11.2 in infancy required a total of 26 hospitalizations during their first year of life. After heart disease, feeding and respiratory problems were the most frequent reasons for intervention.

Premature closure of foramen ovale and renal vein thrombosis in a stillborn twin homozygous for methylene tetrahydrofolate reductase gene polymorphism: a clinicopathologic case study.

Premature closure of the foramen ovale, 4-chamber cardiac hypertrophy, and renal vein/vena cava thrombosis were found at autopsy of a stillborn dizygotic twin at 36 weeks gestational age. Review of the original prenatal sonograms showed features suggestive of early closure of the foramen ovale. Homozygosity for the 5, 10 methylene tetrahydrofolate reductase mutation was shown only in the affected twin after the parents were found to be heterozygous for the mutation. The difference in outcome of the twins following prenatal treatment with beta mimetics and corticosteroids for preterm labor may be related to the added susceptibility factor for thromboembolism associated with presumed hyperhomocysteinemia in the proband which was not shared by the surviving healthy twin. The role of premature closure of the foramen ovale and prenatal treatment are discussed but remain uncertain.

45,X/46,X,r(Y) karyotype transmitted by father to son after intracytoplasmic sperm injection for oligospermia. A case report.

BACKGROUND: The advent of assisted reproductive techniques, such as intracytoplasmic sperm injection (ICSI), has permitted conception and successful pregnancy for an increasing population of infertile men. Approximately 13.7% of infertile men with aspermia and 4.6% with oligospermia have a coexistent chromosome abnormality. Although the ICSI procedure appears safe thus far, early studies are in progress to evaluate outcomes of such pregnancies. For men whose infertility is linked to genetic conditions, it is an unprecedented challenge to predict the potential effects on their offspring. CASE: At 18 weeks' gestation, a 45,X/46,X,r(Y) karyotype was found on genetic amniocentesis performed for advanced maternal age. The pregnancy was achieved by ICSI using sperm from the husband, who was infertile due to severe oligospermia. Subsequently the same karyotype was found in the father. To our knowledge, this is the first reported case of familial transmission of ring Y chromosome. CONCLUSION: It is strongly recommended that ICSI and other new assisted reproductive techniques be preceded by genetic screening for male infertility as well as other indications warranted by the family history since traditional risk assessment may require revision and outcomes may be uncertain in some cases.

Strokes, cutis marmorata telangiectatica congenita, and factor V Leiden.

Cutis marmorata telangiectatica congenita is an uncommon, congenital cutaneous condition typified by persistent cutis marmorata and other associated abnormalities. Progressive neurologic complications are generally not a feature of the disorder. A case is reported of cutis marmorata telangiectatica congenita associated with diffuse cerebrovascular infarcts at 7 months of age. Moyamoya-like vascular abnormalities were demonstrated in addition to the factor V Leiden mutation, a congenital hypercoagulable disorder. This novel case illustrates the importance of evaluating children with strokes for congenital thrombophilic disorders.

Noncompaction of the ventricular myocardium in Melnick-Needles syndrome.

A 4-year-old asymptomatic boy was referred for evaluation after being diagnosed with Melnick-Needles syndrome. Echocardiography demonstrated noncompaction of the left ventricular myocardium as an isolated cardiac finding. Though other structural cardiac defects were reported previously in this syndrome, this is the first report of this rare cardiac anomaly in this likewise rare syndrome. We postulate that this occurrence represents a primary disorder of early fetal development. Patients with Melnick-Needles syndrome should be evaluated for noncompaction of the ventricular myocardium and its potential cardiovascular dysfunction.

New insights into the phenotypes of 6q deletions.

Deletions of chromosome 6q are rare. We report 3 new patients with 6q deletions. Case 1 is a male with an interstitial deletion [del(6)(q13q14.2)], hypotonia, speech delays, and minor anomalies. Case 2 is a male with an interstitial deletion [del(6)(q16.2q22.32)] and malformations, including truncus arteriosus and bilateral oligodactyly. Case 3 is a male with a terminal deletion [del(6)(q25.2)] with retinal pits, hydrocephalus, atrioventricular canal, and hydronephrosis. The findings in our patients and those from 57 previously reported cases demonstrated 3 phenotypic groups associated with 6q deletions. Group A [del(6)(q11-q16)] had a high incidence of hernias, upslanting palpebral fissures, and thin lips with lower frequency of microcephaly, micrognathia, and heart malformations. Group B [del(6)(q15-q25)] was associated with increased intrauterine growth retardation, abnormal respiration, hypertelorism, and upper limb malformations. Group C [del(6)(q25-qter)] was associated with retinal abnormalities, cleft palate, and genital hypoplasia. The only universal finding among all patients with 6q deletions was mental retardation. Other findings common to all 3 groups included ear anomalies (90%), hypotonia (82%), and postnatal growth retardation (68%).

Ultrasound and genetic features of a term triploid pregnancy.

A 69,XXY triploid term infant is reported to demonstrate the prenatal sonographic findings of first trimester intrauterine growth retardation as an important early indicator of this diagnosis. Progressive lag in early sonographic dating for gestational age should raise suspicion of triploidy, which can lead to an early diagnosis, genetic counseling, and a realistic management plan.

A familial MCA/MR syndrome due to translocation t(10;16) (q26;p13.1): report of six cases.

A minute familial translocation t(10;16) (q26;p13.1) was detected in a family with 6 affected children in 2 generations and 9 carriers in 3 generations. This apparently unique translocation is associated with a deleterious syndrome which includes fetal hydrops, ascites, complex congenital heart defect, psychomotor retardation, failure to thrive, hypotonia, narrow palpebral fissures, abnormally modeled, apparently low-set ears, cleft palate, thumb abnormalities, hypogenitalism, inguinal hernia, and sparse hair. All children of known or presumed carriers have been either balanced or unbalanced carriers of this translocation.

Spontaneous resolution of fetal cystic hygroma and hydrops in Turner syndrome.

On a routine ultrasound examination, a cystic hygroma and hydrops were noted at 21 weeks' gestation in a fetus with a 45,X karyotype. Serial studies demonstrated a marked reduction in the size of the cystic hygroma and complete resolution of ascites. At birth, the term infant had features characteristic of the Turner syndrome, including a webbed neck. A critical coarctation of the aorta required repair in the neonatal period. Our case provides glimpses of the intrauterine evolution of the Turner phenotype. We suggest that the possibility of survival when such lesions are detected prenatally may be greater than previously thought.

Prominent transverse (Bowdler) bone spurs as a diagnostic clue in a case of neonatal hypophosphatasia without metaphyseal irregularity.

Transverse midshaft spurs allowed a diagnosis of hypophosphatasia in a newborn infant without metaphyseal irregularity.

Comparative diagnostic value of phenylalanine challenge and phenylalanine hydroxylase activity in phenylketonuria.

Serum phenylalanine (phe) concentrations during and following phe challenges and liver phenylalanine hydroxylase (PH) activity were compared in 13 phenylketonuric (PKU) patients. These patients were separated into two groups: eight patients with no detectable PH activity (PH degrees) and five patients with residual PH activity (PH-) ranging from 9 to 24% of the activity obtained in 10 non-PKU subjects. The rise in serum phe concentration during 3 days of oral loading did not differentiate the two groups. However, the difference in serum phe concentration of the PH degrees and PH- groups reached statistical significance at 24 h postloading (p less than 0.01). We concluded that combined results from multiple measurements during the oral challenge, namely serum phe concentration after termination of loading, serum phe clearance rate, post-loading phe tolerance index and urinary metabolite excretion, make a better indicator for predicting residual PH activity for the majority of PKU subjects than peak phe concentrations during phe challenge.

Reduction of cerebrospinal fluid phenylalanine after oral administration of valine, isoleucine, and leucine.

A supplement of the branched chain amino acids, valine, isoleucine, and leucine (VIL) was administered orally to patients with phenylketonuria, either together with unrestricted diet of natural protein or with a low phenylalanine diet. The VIL supplement brought about a significant reduction of the cerebrospinal fluid-serum ratio of phenylalanine from a mean value of 0.254 without VIL to 0.204 with VIL. The reduction varied from 15-40% (mean 21%). Concentrations of glycine, lysine, methionine, threonine, tryptophan, and tyrosine were within normal limits in serum and cerebrospinal fluid of infants with phenylketonuria. No amino acid imbalance was created by the supplement and no adverse effects from VIL were observed.

Diagnosis of phenylalanine hydroxylase deficiency (phenylketonuria).

Needle liver biopsies were carried out on patients with phenylketonuria (PKU) to establish a diagnosis either of partial or complete phenylalanine hydroxylase (PH) deficiency. Ten phenylketonuric patients and two parents were studied. Nine of the ten patients had completed a three-day oral phenylalanine challenge. Each met the accepted criteria as having classic PKU, based on a sustained rise in the serum phenylalanine level greater than 20 mg/dL. A diagnosis of classic PKU was confirmed in six patients by the absence of hepatic PH activity. Four of the PKU patients had PH activity ranging from 9% to 24% of that found in liver from non-PKU control subjects. The two parents had 27% and 42% of the PH activity found in the control subjects; their child had no activity. Current methods for distinguishing partial from complete PH deficiency are not always reliable, and the degree of the deficiency can best be established by direct measurement of the enzyme in liver.

Intellectual development and academic achievement of children treated early for phenylketonuria.

Twenty early-treated children with classical phenylketonuria (PKU), five early-treated children with variant PKU and seven untreated children with hyperphenylalinemia were compared with non-PKU family members in terms of intellectual development, and 14 school-age PKU children were also compared for academic achievement. For the early-treated children with classical PKU, mean IQ (98) was within the normal range, but nine of these 20 children had IQ scores more than 1SD below those of family members. There was a significant negative correlation between phenylalanine concentrations at one to four years of age and later measured intelligence in these early-treated children, but this was probably a consequence of poor dietary control in the early years. The early-treated children with variant PKU and those with hyperphenylalaninemia had IQ scores consistent with those of unaffected family members, but untreated children with variant PKU had scores significantly lower than their own early-treated siblings. Achievement scores of the early-treated PKU children were consistent with their intellectual ability: they and their non-PKU siblings had similar standard scores for reading and spelling, but arithmetic scores were significantly lower for the PKU children. Early-treated children whose diet had been discontinued had achievement scores in all subjects below those predicted from their IQS.

Galactose-1-phosphate accumulation by a Duarte-transferase deficiency double heterozygote.

An infant, suspected of having galactosemia following a positive screening test on dried blood spots, was shown to be a Duarte-transferase deficiency compound heterozygote through studies of electrophoretic mobility of the transferase enzyme in blood from the patient and family members. No rise in blood glucose was seen following oral ingestion of galactose. At the same time, galactose rose in plasma and was excreted in the urine; galactose-1-phosphate accumulated in erythrocytes. A galactose-free diet was considered the prudent course in the presence of the patient's inability to metabolize galactose completely.

Cat eye syndrome. Partial trisomy 22 due to translocation in the mother.

We describe a case of cat eye syndrome with 47,XX, +22q--. A balanced translocation, 46,XX,t(11;22), was found by banding studies in the mother. The clinical and cytogenetic correlations disclosed by a review of sporadic and familial cases illustrate the heterogeneity of the syndrome and the challenge to genetic counseling.

Pathologic features of the eye in Down's syndrome with relationship to other chromosomal anomalies.

A 2,990-g newborn female mongoloid had narrow palpebral fissures with a mongoloid slant and Brushfield's spots. Pathologic ocular findings resembled those found in patients with trisomy 21 syndrome. Many lesions reflected excessive genetic material and qualitatively resembled those lesions in trisomy 13 and 18 syndromes.