Pediatirc/ Genetics (1)

common, with 2% of live-born babies having a significant congenital malformation and about 5% a genetic disorder
burdensome to the affected individual, family and society, as many are associated with severe and permanent disability

1. Single gene mutations,((Mendelian disorders)

2. Chromosomal disorders
3. Multifactorially inherited conditions
4. Disorders that show an unusual pattern of inheritance
5. Teratogenically caused conditions

Disorders with these patterns of inheritance, described by Mendel in 1865, are rare individually, but collectively numerous, with over 15 000 single gene traits or disorders described
There are three classic forms of genetic inheritance: autosomal dominant, autosomal recessive, and X-linked


This is the most common mode of Mendelian inheritance Autosomal dominant inheritance is determined by the presence of one abnormal gene on one of the autosomes (chromosomes 1–22). Male and female offspring each have a 1 in 2 (50%) chance of inheriting the abnormal gene from an affected parent

Tuberous sclerosis

Marfan syndrome
Neurofibromatosis
Huntington's disease
Retinoblastoma
Waardenburg syndrome
Myotonic dystrophy
Familial hypercholestrolemia (LDL receptor defect Type IIa)
Adult polycystic kidney disease
von Hippel Lindau
Familial adenomatous polyposis and Peutz Jeghers Syndrome
Hereditory spherocytosis
Achondroplasia
Ehlor's Danlos (vascular type)
Acute intermittent porphyria
Hypertrophic Obstructive Cardiomyopathy (HOCM)
Von Willebrand Disease
Polydactyly
Osteogenesis Imperfecta (Except Type VII)
Hereditary hemorrhagic telengiactasia (Osler-weber-rendu syndrome)
Osteopetrosis Type II (Adult type)
Hypokalemic Periodic Paralysis

Within a family, some affected individuals may manifest the disorder mildly and others more severely. For example, a parent with tuberous sclerosis may have mild skin abnormalities only, but his or her affected child may have, in addition, epilepsy and learning difficulties.

Refers to the lack of clinical signs and symptoms in an individual who must have inherited the abnormal gene. An example of this is otosclerosis, in which only about 40% of gene carriers develop deafness


A new mutation in one of the gametes leading to the conception of the affected person. This is the most common reason for absence of a family history in dominant disorders, e.g. >80% of individuals with achondroplasia have normal parents.

Trait appears in every generation

Each child of an affected parent has a 1 in 2 chance of being affected
Males and females are equally affected
Male-to-male transmission occurs

Achondroplasia

achondroplasia is the most common skeletal dysplasia in humans. The bony abnormalities in achondroplasia lead to short stature, macrocephaly, a flat midface with a prominent forehead, and rhizomelic shortening of the limbs.

Clinical symptoms mostly involve three systems: cardiac, musculoskeletal, and ophthalmologic. Musculoskeletal findings include dolichostenomelia (a tall, thin body habitus), arachnodactyly (spider-like fingers and toes), abnormalities of the sternum (pectus excavatum or carinatum), kyphoscoliosis, pes planus, and joint laxity


Eye findings include high myopia, which eventually can lead to vitreoretinal degeneration; an abnormal suspensory ligament of the lens, which can lead to ectopia lentis (dislocation of the lens; in Marfan syndrome, the lens usually dislocates upward and outward); and cataracts. Cardiac findings include a weakened aortic wall, which leads to progressive dilation of the aortic root. Aortic insufficiency followed ultimately by aortic dissection is a common complication of this disorder