P. Franceschini

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Arterial tortuosity syndrome

We describe a patient with arterial tortuosity syndrome (ATS), a rare disorder comprising generalized tortuosity and elongation of all major arteries, soft skin, joint laxity, severe keratoconus, and diffuse tortuosity of the carotids and of intracranial arteries. The patients probably affected brother and sister died at an early age. Cytochemical studies excluded Ehlers-Danlos type IV and type VII syndromes. We review 11 previously described patients.

Macrocephaly–cutis marmorata telangiectatica congenita without cutis marmorata?

We report on two patients with clinical manifestations consistent with a diagnosis of macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC). Both showed macrocephaly with high forehead, overgrowth, capillary hemangiomata involving philtrum, nose, and lips, and redundant skin. In addition, the first had cutis marmorata and joint laxity. The second had postaxial polydactyly of hands and feet, cutaneous syndactyly of third and fourth right fingers and of second and third right toes without evident cutis marmorata. A magnetic resonance imaging scan showed cerebral alterations in both patients. The first had bilateral cortical dysplasia with frontal bilateral myelinization defect of corona radiata. The second had mild intertonsillar widening, cavum septi pellucidi, small porencephalic areas in the anterolateral region of cellae, and subsequently developed a nonobstructive hydrocephalus. Reviewing all reported cases we propose a new criterion for M-CMTC diagnosis.

Oro-facial-digital syndrome II. Transitional type between the Mohr and the Majewski syndromes: report of two new cases

Two patients with the oro‐facial‐digital syndrome II or Mohr syndrome presented laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet. Those rare malformations are typically observed in patients with the Majewski syndrome, a lethal, short rib‐polydactyly skeletal dysplasia with orofacial findings almost identical to those of the Mohr syndrome. Phenotypic overlap between the Mohr and the Majewski syndromes has already been reported in the literature, and it has been suggested that the two syndromes may be mild and severe expressions of the same autosomal recessive disorder. Our two cases give further support to this hypothesis.

Distinctive hair changes (pili torti) in Rapp-Hodgkin ectodermal dysplasia syndrome.

An 8‐year‐old girl with narrow nose, small mouth, maxillary hypoplasia, cleft palate, hypodontia and hypohidrosis is described. Her scalp hair was coarse, dry and wiry. Microscopic examination showed the hair to be twisted at irregular intervals on its long axis, as seen in pili torti. Her mother has the same features; as a child, she had identical hair and is now bald. Both mother and daughter display signs and symptoms of Rapp Hodgkins ectodermal dysplasia. The autosomal dominant inheritance of the disease is further supported by the findings in this family.

Bladder carcinoma in Costello syndrome : Report on a patient born to consanguineous parents and review

We report on a 12-year-old boy with Costello syndrome born to consanguineous (first cousins once removed) parents, supporting the hypothesis of recessive transmission of this syndrome. At age 11 years, the patient developed a bladder carcinoma, a rare pediatric tumor not previously described in Costello syndrome. This suggests that an increased risk of malignancy may be part of this condition.

Variability of clinical and immunological phenotype in immunodeficiency-centromeric instability-facial anomalies syndrome. Report of two new patients and review of the literature.

Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a condition characterized by variable combined immunodeficiency, developmental delay, facial anomalies and a variety of structural chromosomal rearrangements. Recently, aberrations at the molecular level have been described consisting of alterations in the methylation pattern of classical satellite DNA. To our knowledge 15 subjects have been described so far in the literature showing marked phenotypic variability. We report on two new patients with normal development and some peculiar clinical and immunological manifestations. All patients previously reported in the literature are reviewed.ConclusionThe identification of these two cases among our hypogammaglobulinaemic patients suggests that ICF syndrome is not a rare disorder and it should be always taken into account in immunodeficient patients with facial abnormalities.

The effect of phytohaemagglutinin on the metabolism and γ-globulin synthesis of human lymphocytes

Abstract The effect of phytohaemagglutinin on the metabolism of purified lymphocytes from human peripheral blood has been studied. The results show that phytohaemagglutinin stimulates the rate of glycolysis, nucleic acid synthesis as measured by the incorporation of 32P into RNA and DNA, and protein synthesis. The synthesis of γ-globulins is also stimulated, but to a smaller extent than the synthesis of other cellular proteins. The results are discussed in relation to the previously described effects of phytohaemagglutinin on antibody synthesis and lymphocyte transformation.

Interstitial deletion of the long arm of chromosome 2 (q31q33) in a girl with multiple anomalies and mental retardation

Three cases of interstitial deletion of the long arm of chromosome 2 have been described up to date (Warter et al. 1976; Fryns et al. 1977; Taysi et al. 1981). The deleted segment was different in each instance, and so was the phenotype. We have observed an l 1-year-old female with a 2q31q33 deletion (Fig. 1) and the following clinical findings: mental retardation, short stature, microphthalmia, ptosis, antimongoloid slant of the palpebral fissures, cleft palate prominent nose, maxillary and mandibular hypoplasia, camptodactyly of the third, fourth and fifth fingers, hyperextensible index fingers, and syndactyly of the second, third, fourth and fifth toes (Fig. 2). Although the cytogenetic finding appears to be the same as in the patient described by Taysi et al. (1981), our patient also shares clinical symptoms with the other two cases with different 2q deletion. Obviously, many more cases are required to establish a genotype-phenotype correlation. We are interested in information on such cases.

Interstitial deletion of the long arm of chromosome 7 46,XX,del(7)(pter→q2200::q3200→qter)

SummaryA newborn girl with multiple anomalies had an interstitial deletion of the long arm of chromosome 7 (46,XX,der(7)mat). The patients mother and maternal grandmother were carriers of a balanced translocation, 46,XX, inv ins(5;7)(q14;q3200q2200). Both cytogenetic and clinical findings were similar to those in the two cases already described.