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Introduction The most common form of spinal muscular atrophy (SMA) is a recessive disorder caused by SMN1 mutations in 5q13, whereas the genetic etiologies of non-5q SMA are very heterogenous and largely remain to be elucidated. We present a father and son with atrophy and weakness of the lower leg muscles since infancy. Genetic studies in this family revealed a novel BICD2 mutation causing autosomal dominant lower extremity-predominant SMA type 2. Patients The proband was the father, aged 30, and the son was aged 3. Both of them were born uneventfully to nonconsanguineous parents. While the father first walked at the age of 19 months, the son was unable to walk at age 3 years. In both, knee and ankle reflexes were absent and sensation was intact. Serum creatine kinase levels were normal. The son showed congenital arthrogryposis and underwent orthopedic corrections for talipes calcaneovalgus. Investigation of the father at the age of 5 years revealed normal results on nerve conduction studies and sural nerve biopsy. Electromyography showed chronic neurogenic change, and muscle biopsy showed features suggestive of denervation. The father was diagnosed clinically with a sporadic distal SMA. Follow-up studies showed very slow progression. Investigations and results Next-generation and Sanger sequencing revealed a deleterious mutation in BICD2: c.1667A>G, p.Tyr556Cys, in this family. Discussion BICD2 is a cytoplasmic conserved motor-adaptor protein involved in anterograde and retrograde transport along the microtubules. Next-generation sequencing will further clarify the genetic basis of non-5q SMA.

We describe a very unusual combination, and previously unreported, of malformations in an 18-week, spontaneously aborted male fetus. The fetus had a reversed dorsoventral positioning of the head and upper limbs relative to the body axis with the head and both upper limbs directed dorsally, and an abrupt rotation of the vertebral bones at the level of CZ The fetus also had asplenia, single ventricle, and conotruncus. The fetus also had flexion deformities at the wrist, reduction deformity of the left second digit, anomalies in ossification of the bones of the left hand, and bilateral talipes calcaneovalgus. The major malformations in this fetus were all blastogenetic in origin and consisted of dorsoventral patterning defect involving structures cranial to C7, a laterality, and a septation defect of the ventricle and outflow tract of the heart. The defects are interpreted as being the result of abnormal coordination of the molecular signaling involved in dorsoventral axis formation and laterality of the limbs and trunk, and possibly also in cardiac septation.

Objectives: To evaluate the association between large for gestational age (LGA) and demographic and medical risk factors as well as specific types of congenital anomalies. Study design: A retrospective, case-control study on 2,149,617 consecutive births was conducted. LGA was defined as 1.64 SD above the mean weight for gestational age, adjusted by sex and altitude. Risk factor frequency distributions were compared between LGA and normal birth weight neonates.Associations between LGA and 41 infants with isolated congenital anomalies were evaluated. Results: Of 31,897 neonates with congenital anomalies, 1800 were LGA. Five anomalies were associated with LGA: talipes calcaneovalgus, hydrocephaly, combined angiomatoses, hip subluxation, and non-brown-pigmented nevi. Multiparity, vaginal bleeding, diabetes, and delivery by cesarean section were more frequent in LGA than in appropriate for gestational age infants' mothers. Several maternal but no paternal factors were statistically associated with an increased risk for LGA infants. Conclusions: The clinical observation that nevi are more commonly observed in LGA patients was supported. The higher frequencies of hip subluxation and talipes calcaneovalgus among LGA neonates reinforces their pathogenesis as deformations, whereas those of combined angiomatoses and hydrocephaly could reflect increased fluid or body mass. (J Pediatr 2002; 140:200-4)

Twelve patients with residual talipes calcaneovalgus deformity due to poliomyelitis were reviewed. A two-stage Elmslie's arthrodesis was performed on nine patients with rigid deformity. Tendon transfer (peroneus brevis in one, peroneus brevis and longus in two) to the tendo Achillis insertion is used to correct the calcaneus deformity, after reduction of the calcaneus in the subtalar joint, using a Steinmann pin passed through the calcaneus. Good results were obtained in patients treated by arthrodesis. However, the deformity recurred in patients treated only with tendon transfer.

A case of partial deletion of chromosome No. 13 identified by G banding as 46, XX, del(13)(q21--ater) is reported in an infant with severe microcephaly, microphthalmos, talipes calcaneovalus, and a single crease on each of the little fingers. A review of other cases of chromosome No. 13 deletion that were identified by banding is presented and the correlation between clinical features and deletion of specific bands is discusses.

We describe a congenital deformity of the foot which is characterised by calcaneus at the ankle and valgus at the subtalar joint; spontaneous improvement does not occur and serial casting results in incomplete or impermanent correction of the deformities. Experience with five feet in four children indicates that release of the ligaments and tendons anterior and lateral to the ankle and lateral to the subtalar joint is the minimum surgery necessary; subtalar arthrodesis may be required in addition. The foot deformity described may occur as an isolated condition or in association with multiple congenital anomalies. The possibility of a neurological deficit should always be excluded.

THREEEE female children we have observed have certain anomalies of the external genitalia which do not correspond to any known type of genital malformation. Report of Cases Case 1.—An immature newborn child weighed 2,100 gm (4 lb 9 ounces) and was 44 cm (17 inches) long. Death occurred approximately 24 hours after delivery. The child was found to be chromatin-positive. Postmortem findings revealed proximal tracheoesophageal fistula, defect of ventricular septum approximately 2 mm in diameter, talipes calcaneovalgus, epicanthus, and malformation of pinnae. Adrenal glands, ovaries, and uterus were normal. External genitalia were malformed (Fig 1). On each side, laterally and superior to the external vaginal opening, were two cutaneous lobules measuring approximately 3 × 2 × 1 cm. The vagina was prolapsed and its opening partially covered with two cutaneous duplications which extended from the elevated phallic region. The urethral opening was between them and above the opening of the