Mendelian Inheritance in Man

Fibular aplasia and/or hypoplasia is documented as a developmental field defect and the extent of the fibular developmental field is delineated. The term fibular a/hypoplasia denotes the clinical spectrum of fibular deficiency in different patients and also implies that aplasia can be present in one limb and hypoplasia in the other. Causal heterogeneity of fibular a/hypoplasia is demonstrated, thereby defining it as a developmental field defect. Most cases of fibular a/hypoplasia are isolated, sporadic events. An autosomal dominant form of isolated fibular a/hypoplasia with ankle joint anomaly is reviewed. Fibular a/hypoplasia may be part of more complex sporadic dysostoses; sporadic syndromes, an aneuploidy syndrome; several autosomal dominant and autosomal recessive conditions. Fibular a/hypoplasia is also postulated to occur as a result of disruption or teratogenic insult; in animals, fibular development can be disturbed by radiation, busulfan, and retinoic acid. Clinical data allow evaluation of the extent of the fibular developmental field of the lower limb. This appears to include the pubic portion of the pelvis, proximal femur (distal half being apparent tibial developmental territory), patella, anterior cruciate ligament, and lateral and/or axial foot rays (but "never" the hallux and almost never associated with polydactyly). The rare cases of fibuloulnar dimelia allow confirmation of the well known homology of mesomelic limb segments responsible for concordant ulnar and fibular (and radial and tibial) defect, if both upper and lower limbs are involved in a given condition. Because fibular a/hypoplasia is the commonest of the mesomelic paraxial hemimelias, is usually nonsyndromal, and in most cases is apparently nongenetic (ie, with negligible recurrence risk), we propose that in humans, as in several other tetrapods, the fibula is undergoing regressive evolution and hence is developmentally especially labile.

Fibular a/hypoplasia: review and documentation of the fibular developmental field

Kuwait has a cosmopolitan population of 1.7 million, mostly Arabs. This population is a mosaic of large and small minorities representing most Arab communities. In general, Kuwait's population is characterized by a rapid rate of growth, large family size, high rates of consanguineous marriages within the Arab communities with low frequency of intermarriage between them, and the presence of genetic isolates and semi-isolates in some extended families and Bedouin tribes. Genetic services have been available in Kuwait for over a decade. During this time it has become clear that Arabs have a high frequency of genetic disorders, and in particular autosomal recessive traits. Their pattern is unique and some disorders are relatively common. Examples are Bardet-Biedl and Meckel syndromes, phenylketonuria, and familial Mediterranean fever. A relatively large number of new syndromes and variants have been delineated in Kuwait's population, many being the result of homozygosity for autosomal recessive genes that occurred because of inbreeding. Some of these syndromes have subsequently been found in other parts of the world, negating the concept of the private syndrome. This paper provides an overview of autosomal recessive disorders among the Arabs in Kuwait from a personal perspective and published studies, and highlights the need for genetic services in Arab countries with the goal of prevention and treatment of genetic disorders.

https://jmg.bmj.com/content/jmedgenet/31/3/224.full.pdf

Autosomal recessive disorders among Arabs: an overview from Kuwait.

Familial aggregates of the most common disorders of mullerian differentiation in females—Mullerian aplasia, incomplete Mullerian fusion—are best explained on the basis of polygenic/multifactorial inheritance. No information exists on the number and chromosomal location of responsible genes. Single mutant genes (Mendelian) are responsible for the McKusick-Kaufman syndrome (MKS) and the hand-foot-genital syndrome. The molecular basis for the latter condition involves HOXA13, but the molecular basis of MKS and other disorders of the female reproductive ducts is unknown. Vaginal atresia, Mullerian aplasia, and incomplete Mullerian fusion are not infrequently observed in malformation syndromes. Am. J. Med. Genet. (Semin. Med. Genet.) 89:224–239, 1999. © 2000 Wiley-Liss, Inc.

Genetics of the female reproductive ducts

Summary:  Purpose: We analyzed databases on chromosomal anomalies and epilepsy to identify chromosomal regions where abnormalities are associated with clinically recognizable epilepsy syndromes. The expectation was that these regions could then be offered as targets in the search for epilepsy genes.



Methods: The cytogenetic program of the Oxford Medical Database, and the PubMed database were used to identify chromosomal aberrations associated with seizures and/or EEG abnormalities. The literature on selected small anomalies thus identified was reviewed from a clinical and electroencephalographic viewpoint, to classify the seizures and syndromes according to the current International League Against Epilepsy (ILAE) classification.



Results: There were 400 different chromosomal imbalances described with seizures or EEG abnormalities. Eight chromosomal disorders had a high association with epilepsy. These comprised: the Wolf–Hirschhorn (4p-) syndrome, Miller–Dieker syndrome (del 17p13.3), Angelman syndrome (del 15q11-q13), the inversion duplication 15 syndrome, terminal deletions of chromosome 1q and 1p, and ring chromosomes 14 and 20. Many other segments had a weaker association with seizures. The poor quality of description of the epileptology in many reports thwarted an attempt to make precise karyotype–phenotype correlations.



Conclusions: We identified certain chromosomal regions where aberrations had an evident association with seizures, and these regions may be useful targets for gene hunters. New correlations with specific epilepsy syndromes were not revealed. Clinicians should continue to search for small chromosomal abnormalities associated with specific epilepsy syndromes that could provide important clues for finding epilepsy genes, and the epileptology should be rigorously characterized.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1528-1157.2002.19498.x

Chromosomal abnormalities and epilepsy: a review for clinicians and gene hunters.

A newly recognised profound limb deficiency malformation syndrome in two Arab sibs of different sexes with consanguineous parents is described. Additional features, which include thoracic dystrophy, unusual facies, and normal intelligence, are consistent in both of them. Autosomal recessive inheritance is suggested.

https://jmg.bmj.com/content/jmedgenet/22/1/36.full.pdf

Profound limb deficiency, thoracic dystrophy, unusual facies, and normal intelligence: a new syndrome.

We present a family with numerous first cousin marriages and several members affected with spondyloepiphyseal dysplasia tarda with progressive arthropathy causing severe crippling and deformity. The extensive pedigree provides strong evidence for autosomal recessive inheritance.

https://jmg.bmj.com/content/jmedgenet/21/3/193.full.pdf

Spondyloepiphyseal dysplasia tarda with progressive arthropathy.

A child with a de novo interstitial deletion, 46,XX,del(2)(q31q33), is described. Clinical features included psychomotor retardation, hypotonia, microcephaly, hypertelorism, downward slanting palpebral fissures, macrostomia, cleft palate, micrognathia, abnormal ears, overlapping fingers, simian creases, and rocker bottom feet.

https://jmg.bmj.com/content/jmedgenet/20/6/464.full.pdf

K Naguib

Papers

Profound limb deficiency, thoracic dystrophy, unusual facies, and normal intelligence: a new syndrome.

Spondyloepiphyseal dysplasia tarda with progressive arthropathy.

Interstitial deletion of the long arm of chromosome 2: del(2)(q31q33).