Jürgen Herrmann

The SC phocomelia and the Roberts syndrome: Nosologic aspects

We reviewed the SC phocomelia syndrome (SCS) and the Roberts syndrome (RS) to demonstrate techniques of nosologic analysis based primarily on the phenotype analysis. We considered the type, localization, severity, and variability of the manifestations. In this patient sample these techniques are not sensitive enough to rule out any one of the three most likely etiologic hypotheses, namely whether the SCS and the RS are due to different recessive genes, different alleles, or the same recessive gene. However, this study does suggest certain implications for each of these possibilities.

Short rib-polydactyly (SRP) syndromes, types Majewski and Saldino-Noonan

Four examples of short rib-polydactyly syndromes are described. Case 1 represents the Majewski type, and the other three are examples of the Saldino-Noonan type. Both conditions are true multiple congenital anomaly syndromes and neonatally lethal forms of dwarfism with a narrow thorax, polydactyly and associated visceral malformations. They are probably caused by the homozygous state of different autosomal recessive genes. They must be differentiated from similar conditions such as chondroectodermal dysplasia, asphyxiating thoracic dysplasia, the Meckel syndrome and the trisomy 13 syndrome.The short rib-polydactyly syndrome type Majewski is characterized by thoracic dystrophy, pre- and postaxial polydactyly, mesomelic brachymelia and cleft lip and/or palate. Skull, vertebral column and pelvis are not markedly affected. Associated features include polycystic kidneys, hypolastic epiglottis and lungs, and various malformations of the cardiovascular system, genitalia and the central nervous system.The short rib-polydactyly syndrome type Saldino-Noonan is characterized by thoracic dystrophy, postaxial polydactyly, severely shortened, flipper-like extremities and a striking metaphyseal dysplasia of the tubular bones. The ossification of the calvaria, vertebral column, pelvis and short bones of the hands and feet is defective. Associated features occurring in varying frequency include polycystic kidneys, transposition of the great vessels and atretic lesions of the gastrointestinal and genitourinary systems.ZusammenfassungEs wird über 4 Fälle mit Thoraxdysplasie-Polydaktylie-Syndromen berichtet. Fall 1 wird dem Majewski-Typ, die Fälle 2–4 werden dem Saldino-Noonan-Typ dieser Syndrome zugeordnet. Es handelt sich um letale Zwerg-wuchsformen mit eigenartigen Mißbildungsmustern. Sie sind wahrscheinlich durch Homozygotie autosomal recessiver Gene bedingt. Differentialdiagnostisch sind sie in erster Linie von der chondroektodermalen Dysplasie (Ellis-van Creveld-Syndrom), der asphyxierenden Thoraxdysplasie, dem Meckel-Syndrom und der Trisomie 13 abzugrenzen.Der Majewski-Typ der Thoraxdysplasie-Polydaktylie-Syndrome ist charakterisiert durch kurze Rippen, prä- und postaxiale Polydaktylie, eine mesomele Brachymelie und Spaltbildungen im Lippen-Kiefer-Gaumen-Bereich. Weitere Merkmale sind Nierencysten, eine Hypoplasie von Epiglottis und Lungen, verschiedene Fehlbildungen von Herz, großen Gefäßen, Zentralnervensystem und Genitalien.Der Saldino-Noonan-Typ der Thoraxdysplasie-Polydaktylie-Syndrome ist gekennzeichnet durch kurze Rippen, postaxiale Polydaktylie, eine schwere Verkürzung der Gliedmaßen und eine ausgeprägte metaphysäre Dysplasie der Röhrenknochen. Es bestehen erhebliche Ossifikationsstörungen der kurzen Röhrenknochen, leichtere der Schädelkalotte und Wirbelkörper. Das Becken ähnelt dem bei der chondroektodermalen Dysplasie und der asphyxierenden Thoraxdysplasie. Begleitfehlbildungen sind Nierencysten, Transposition der großen Gefäße und Atresien im Bereich des Gastrointestinal- und Urogenitaltrakts.

Studies of malformation syndromes of man XXIX: The Wiedemann-Beckwith syndrome

This report describes 12 patients with the Wiedemann-Beckwith syndrome (WBS), including 6 familial cases from 2 families. The clinical manifestations do not allow for a differentiation between familial and sporadic cases. Consistent morphologic features include organomegaly, cytomegaly nd nucleomegaly. The pathogenetic process may involve few or many organs and tissues and may represent a nuclear/mitotic dysfunction. Clinically, the manifestations are hyperplasia, hypoplasia, dysplasia, neoplasia and defects in differentiation. Secondary functional disturbances are at times prominent.The differential diagnosis of the WBS includes 1) the Wilms tumor (WT)-aniridia syndrome; 2) the “tumor-hypertrophy syndrome” which includes WT, adrenocortical tumors or hepatoblastoma; 3) the WT-pseudohermaphroditism syndrome; and 4) the “tumor-nevus syndrome” with or without malformations (particularly duplications) of the urinary tract. The latter two conditions are apparently not associated with hemihypertrophy.Familial occurrence suggests that some cases of the WBS may be due to delayed mutation. Carriers of the premutated allele appear to belong to two classes: those with a high risk of producing affected offspring and those who transmit the premutated allele but have no affected offspring.

Terminological, diagnostic, nosological, and anatomical-developmental aspects of developmental defects in man.

Man’s experience of congenital malformations antedates recorded history and can be inferred from philology and the most ancient of legends. Indeed, the presence of Down syndrome in the chimpanzee (McClure et al., 1969, 1970) and of various X-linked disorders in other mammals (Ohno, 1967) means that even during phylogeny man lived side by side with mammalian cousins affected with homologous forms of his own genetic aberrations. The history of teratology has been written many times and is astoundingly voluminous (Gruber, 1964). It shows that the accomplishments of the early workers in the field consisted primarily of anatomical and clinical descriptions.

Arthro-dento-osteo dysplasia (Hajdu-Cheney syndrome)

From one personal patient and thirteen reported in the literature, arthro-dento-osteo dysplasia (ADOD) is defined as a heritable connective tissue disorder with the main clinical manifestations of laxity of joints, early loss of teeth, and multiple osteolytic lesions, including acro-osteolysis, on roentgenographic examination. These lesions are likely to represent “pseudo-osteolysis” with faulty primary bone formation rather than true osteolysis of previously normal bone.ADOD is an example of relational pleiotropism with most clinical manifestations representing secondary effects and deformities. The cranial sutures frequently remain uncalcified and contain multiple Wormian bones. Secondary deformities may be progressive and affect primarily the skull, spine, fingers and fingernails. Pathologic fractures are clinically the most important manifestation of ADOD.In one family the mother and four of her six children were affected. The other nine case reports describe sporadic instances. ADOD is presumed to be caused by an autosomal dominant gene, the sporadic cases representing new mutations.

Delayed Mutation as a Cause of Genetic Disease in Man: Achondroplasia and the Wiedemann-Beckwith Syndrome

The concept of delayed mutation was developed by Auerbach1 (1956) to explain the sudden occurrence of the same autosomal dominant mutation in collateral relatives. Auerbach postulated that the “connecting” unaffected ancestors of the affected individuals transmitted a labile premutated allele which, by delayed mutation, gave rise to the (fully) mutant allele. In unaffected offspring of such carriers the premutated allele could either have remained premutated or have reverted to a stable allele with normal phenotype. Auerbach had observed this phenomenon previously in Drosophila; she noted a pedigree of human extrodactyly when she suggested the possibility also in man.l Here we should like to describe some general aspects of the model of delayed mutation, using achondroplasia and the Wiedemann-Beckwith syndrome as specific examples.

Studies of malformation syndromes in man XXXVI: the Pfeiffer syndrome, association with Kleeblattschädel and multiple visceral anomalies

This paper reports sporadic occurrence of the Pfeiffer syndrome with Kleeblattschädel (KS) in a male infant who died at 6 months of pneumonia with signs of increased intracranial pressure and who was found to have hydrocephalus, polymicrogyria, cerebellar herniation, bicuspid aortic valve, a common mesentery, absence of lesser omentum, hypplasia of gallbladder, a single umbilical artery, and multiple eye defects. This case is presumed to represent a new mutation: in other families the Pfeiffer syndrome has been dominantly inherited. The Pfeiffer syndrome is a form of acrocephalosyndactyly and impresses clinically as a mild form of the Apert syndrome. The Kleeblattschädel is an etiologically non-specific developmental field defect (DFC); about two fifths of 51 known cases have apparent thanatophoric dwarfism and about one fifth are probable or possible examples of the Pfeiffer syndrome. The KS-DFC has also been seen in the syndromes of Carpenter, Apert and Crouzon.

Immunodeficiency associated with exomphalos-macroglossia-gigantism syndrome

Severe combined immunodeficiency disease was observed with the exomphalosmacroglossia-gigantism(EMG) syndrome in a female infant who died of Pneumocystis carinii pneumonia and intractable diarrhea. Two male siblings of this patient who died in infancy probably had similar immunodeficiency disease but no overt manifestations of the EMG syndrome. This report considers possible etiologic and pathogenetic relationships between the EMG syndrome and the immunodeficiency disorder.

Studies of malformation syndromes of man VB: The hypertelorism-hypospadias (BBB) syndrome

We describe a boy with the hypertelorism-hypospadias (BBB) syndrome. His mother and his maternal grandmother showed minor manifestations suggestive of the syndrome. The BBB syndrome is a syndrome of multiple congenital anomalies with mental retardation due a segregating mendelian mutation, either X-linked or autosomal. This paper reviews the literature on the subject and emphasizes the problem of identifying females at high risk of transmitting the condition.

Studies of malformation syndromes of man XXXXIIB: mother and son affected with the ulnar-mammary syndrome type Pallister.

We report mother and son with the ulnar-mammary syndrome type Pallister: both had postaxial polydactyly in one upper limb and absence or hypoplasia of the axillary apocrine glands bilaterally. The mother had total lack of the mammary gland tissue and absence of one kidney. Her son also had unilateral oligodactyly, an absent ulna and hypoplasia of the ipsilateral shoulder girdle.