New syndrome: Autosomal dominant microcephaly and radio‐ulnar synostosis

Abstract

To date, the combination of microcephaly and radio-ulnar synostosis has not been recognized as a distinct clinical and genetic entity. We report on 4 familial cases with this previously undescribed combination of defects, showing autosomal dominant inheritance (Fig. 1).

Clinical delineation of Giuffrè–Tsukahara syndrome: Another case with microcephaly and radio‐ulnar synostosis with apparent X‐linked semi‐dominant inheritance

“…As Giuffrè et al [1994] noted in their patients, mild psychomotor impairment in the male patients (not reported in the female patients in the second family) leave X-linked semi-dominant inheritance possible as in our family. Further investigations of familiar occurrence of the disorder and of X-inactivation in female patients should be performed in order to obtain more evidence regarding this type of inheritance.…”

“…However, these entities do not seem to be clearly distinguishable. Some of the patients described by Giuffrè et al [1994], Tsukahara et al [1995], as well as our patients show an overlapping phenotype regarding fingers (especially clinodactyly of the fifth fingers, single crease of the fifth finger, webbing between the fingers).…”

“…The patient also showed dysmorphic features: bushy eyebrows, mild synophrys, epicanthal folds, hypoplastic philtrum, thin vermilion border of the upper lip, malaligned permanent teeth, clinodactyly of the fifth fingers, single crease of the right fifth finger and partial webbing of the fingers. The authors discussed the similarities between their family and the first family described by Giuffrè et al [1994]; however, they presumed that the syndrome present in their family was not the same because the patients of Giuffré et al lacked mental retardation, scoliosis, and had a different facial phenotype. Tsukahara et al [1995] did not mention the second family with psychomotor delay in the male patient.…”

“…In the second family described by Giuffrè et al [1994] three members were affected: an 8-year-old boy showed intrauterine growth retardation, psychomotor delay, speech delay, microcephaly, bilateral proximal radio-ulnar synostosis, a prominent nose, a submucous cleft of the palate, shawl scrotum and proximally inserted thumbs. His sister had microcephaly and proximal radio-ulnar synostosis on the right side and an enlarged and morphologically abnormal radial head on the left side.…”

“…To date two families and three sporadic cases were described with a pattern of congenital anomalies which included radio-ulnar synostosis and microcephaly as main features, Giuffrè et al [1994] described a family of one 8-month-old male patient and his sister, mother and grandmother with head circumference below the 3rd centile and radio-ulnar synostosis. Neither mental retardation nor neurological abnormalities were observed in these patients except for the boy who revealed peripheral hypertonia and increased deep tendon reflexes in the lower limbs.…”