Adams-Oliver syndrome (AOS) is characterized by the association of aplasia cutis congenita with terminal transverse limb defects, often accompanied by additional cardiovascular or neurological features. Both autosomal-dominant and autosomal-recessive disease transmission have been observed, with recent gene discoveries indicating extensive genetic heterogeneity. Mutations of the DOCK6 gene were first described in autosomal-recessive cases of AOS and only five DOCK6-related families have been reported to date. Recently, a second type of autosomal-recessive AOS has been attributed to EOGT mutations in three consanguineous families. Here, we describe the identification of 13 DOCK6 mutations, the majority of which are novel, across 10 unrelated individuals from a large cohort comprising 47 sporadic cases and 31 AOS pedigrees suggestive of autosomal-recessive inheritance. DOCK6 mutations were strongly associated with structural brain abnormalities, ocular anomalies, and intellectual disability, thus suggesting that DOCK6-linked disease represents a variant of AOS with a particularly poor prognosis.
We report a boy with a rare association of congenital anomalies including facial dysmorphism with a very large fontanel and cleft palate, thoracic deformity, right-sided aortic arch, hypoplastic genitals, abdominal wall hypoplasia and a very rare umbilical abnormality, previously unreported. All anomalies are positioned on the midline suggesting a midline ventral developmental field defect. Different diagnoses were considered in this patient, including the pentalogy of Cantrell and Donnai-Barrow syndrome. However, none can account for all the abnormalities seen.
We describe a patient with a bilateral fusion of a hypoplastic 5th metacarpal with the 4th metacarpal. Family history was negative and no other abnormalities were noted.A 17-year-old male was seen at the Genetic Clinic with bilateral short, angulated 5th fingers (Fig. 1). There was no syndactyly. He had a normal function of both hands. Family history was normal and apart from the digital abnormality no other malformations were noticed. On X-ray, a hypoplastic 5th metacarpal fused with the fourth metacarpal was noticed. The outline of the hypoplastic 5th metacarpal can be distinguished in the 4th metacarpal ('bone in bone' appearance) (Fig. 2). Ultrasound of the kidneys was normal. Chromosome studies on a peripheral blood lymphocyte culture showed a 46,XY normal male karyotype after G-banding.Fusion of metacarpals 4 and 5 is not a frequent finding in non-syndromic hand malformations. Syndactyly type V (OMIM 186300), one of the rarest forms of nonsyndromic syndactyly, is characterized by fusion of metacarpals 4 and 5 with angulation of digit 5. Different degrees of syndactyly, brachydactyly, split hand, and camptodactyly are also seen [Robinow et al., 1982]. Synostosis between metacarpals 4 and 5 has also been described as an X-linked recessive trait (OMIM 309630) [Orel, 1928;Holmes et al., 1972;Annerén and Amilon, 1994] but other reports suggest autosomal inheritance [Lerch, 1948;Habighorst and Albers, 1965]. A Y-like fusion of metacarpals 4 and 5 has also been observed in patients with a distal 13q deletion [Schinzel, 2001].This report describes a sporadic case of an isolated synostosis between metacarpals 4 and 5. Apart from this fusion no other hand-or foot abnormalities were noted. Since no other family members were affected, this case
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