A recognisable short stature syndrome with premature aging and pigmented naevi.

We report the progress up to the age of seven years of a small for dates baby whose face and neck are strikingly devoid of subcutaneous tissue and who has, in addition, multiple pigmented naevi.     

Microtia and short stature: a new syndrome.

Bilateral microtia, absent patellae, short stature, poor weight gain, and characteristic facial features are described in two female sibs. Other skeletal anomalies included complete habitual dislocation of the elbow, slender ribs and long bones, abnormal modelling of the glenoid fossae with hooked clavicles, and clinodactyly. Bone age was significantly delayed and there was flattening of the epiphyses. This unusual combination of features has many similarities to the syndrome described by Hurst et al.     

Mutations in C-natriuretic peptide (NPPC): a novel cause of autosomal dominant short stature

PurposeC-type natriuretic peptide (CNP) and its principal receptor, natriuretic peptide receptor B (NPR-B), have been shown to be important in skeletal development. CNP and NPR-B are encoded by natriuretic peptide precursor-C (NPPC) and natriuretic peptide receptor 2 (NPR2) genes, respectively. While NPR2 mutations have been described in patients with skeletal dysplasias and idiopathic short stature (ISS), and several Npr2 and Nppc skeletal dysplasia mouse models exist, no mutations in NPPC have been described in patients to date.MethodsNPPC was screened in 668 patients (357 with disproportionate short stature and 311 with autosomal dominant ISS) and 29 additional ISS families in an ongoing whole-exome sequencing study.ResultsTwo heterozygous NPPC mutations, located in the highly conserved CNP ring, were identified. Both showed significant reductions in cyclic guanosine monophosphate synthesis, confirming their pathogenicity. Interestingly, one has been previously linked to skeletal abnormalities in the spontaneous Nppc mouse long-bone abnormality (lbab) mutant.ConclusionsOur results demonstrate, for the first time, that NPPC mutations cause autosomal dominant short stature in humans. The NPPC mutations cosegregated with a short stature and small hands phenotype. A CNP analog, which is currently in clinical trials for the treatment of achondroplasia, seems a promising therapeutic approach, since it directly replaces the defective protein.     

A new recognisable syndrome in three sibs with congenital heart disease, round face with depressed nasal bridge, short stature, and developmental retardation.

We report three sibs with congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, developmental retardation, relatively dark skin, and high axial triradius. The chromosomes of the three patients were normal and the parents were unrelated, healthy, and of normal intelligence. The mother denied infections, drinking, drug intake, or exposure to known teratogenic agents during each pregnancy.     

Agrypnia excitata in a patient with progeroid short stature and pigmented Nevi (Mulvihill-Smith syndrome)

We report the video-polysomnographic sleep characteristics of a 25-year-old woman with the Mulvihill-Smith syndrome, a rare clinical condition characterized by progeria-like aspect, peculiar multiple pigmented nevi, low stature, and cognitive impairment. Among the various exams, two overnight video-polysomnographic recordings were carried out; moreover, cerebral MRI and molecular analysis of the prion protein gene (PRNP) were also performed. The video-polysomnographic recordings showed the absence of clear sleep episodes but the presence of periods during which the patient had poor contact with the environment, stereotyped afinalistic movements of the upper limbs and hands, irregular or periodic breathing (with central apnea episodes), heart rate arrhythmia, and rapid eye movements. Cerebral MRI showed only diffuse mild enlargement of the cortical sulci and the molecular genetics analysis of the PRNP was normal. Our clinical and neurophysiological study seems to indicate that a particular condition of severe sleep disruption, similar to some extent to that reported in the fatal familial insomnia and in the Morvan fibrillary chorea, which has been indicated as Agrypnia Excitata in recent literature, might be associated with the Mulvihill-Smith syndrome. The inclusion of a detailed study on the sleep characteristics of eventual additional patients will certainly help our understanding of this rare condition.     

Hepatoerythropoietic porphyria in a woman with short stature and deformed hands.

A 23-year-old woman from Honduras was diagnosed to have hepatoerythropoietic porphyria. She had photosensitive skin of early onset, hypertrichosis, and severe scleroderma-like lesions of the hands. Erythrocyte uroporphyrinogen decarboxylase activity was reduced to about 10% of the normal activity.     

Frontonasal dysplasia, congenital heart defect, and short stature: a further observation.

We present a mildly retarded boy with frontonasal dysplasia, valvular aortic stenosis, short stature, and small head circumference. In addition, mild genital anomalies and bilateral Sydney lines were present. Strikingly similar cases recently published by de Moor et al suggest a defined clinical entity.     

Brachydactyly C, short stature, and hip dysplasia.

Short stature may be a component of the brachydactyly C syndrome. A family is presented in which the propositus has brachydactyly C, short stature, and hip dysplasia.     

Brachydactyly type A-4 (Temtamy type) with short stature in a Japanese girl and her mother

We report on a Japanese girl and her mother with brachydactyly. Their 2nd and 5th middle phalanges were short and the latter was fused with the distal phalanx in one of the patients. Length and shape of proximal and distal phalanges as well as metacarpals seemed normal. These findings are consistent with brachydactyly type 4-A, which is a rare subtype and has not been adequately documented. Short stature was reported only in some cases of brachydactyly type A-1, A-6, C, and E, but not in the other subtypes. Our patients with type A-4 brachydactyly also had short stature. © 1993 Wiley-Liss, Inc.     

GMS syndrome: a new dominant condition with goniodysgenesis, mental retardation, and short stature.

We describe a mother and daughter with a distinct phenotype that is different from previous reports. This is likely to constitute a new syndrome for which we propose the mnemonic GMS for G goniodysgenesis, M mental deficiency, and S short stature. The pattern of occurrence is compatible with either autosomal dominant or X-linked inheritance.     

Symphalangism, short stature, skeletal anomalies, and accessory testis: a new malformation syndrome.

A 17-year-old Jewish Sephardi male is described with symphalangism, short stature, multiple skeletal anomalies, and an accessory testis, which appears to be a new malformation syndrome of possible genetic aetiology.     

Unknown syndrome: proportionate short stature, mandibular prognathism, and short femoral necks

We describe a young woman with proportionate short stature, short femoral necks, limitation of wrist flexion, and a prominent mandible.     

A report of a child with a deletion (9)(q34.3): a recognisable phenotype?

We report a case of a male infant who presented with congenital anomalies and was found to have a de novo deletion in the terminal region of the long arm of chromosome 9. He died at the age of 17 weeks of cardiorespiratory failure owing to RSV positive bronchiolitis. A review of previously published reports documented one previous report of a patient with a deletion of (9)(q34.3) and multiple congenital anomalies. Comparison with the previously reported case suggests that the phenotype observed constitutes a clinically recognisable pattern of malformations.     

Partial deletion 8q without Langer-Giedion syndrome: a recognisable syndrome.

We report two de novo cases of del(8)(pter----q24.1:) with breakpoints involving the distal part of band 8q24.1. The clinical features were similar and there were no obvious stigmata of Langer-Giedion syndrome (LGS). There are three other cases reported with a deletion of chromosome 8 at approximately the same breakpoint, one without LGS and some similarities to our cases, the other two with LGS. Our findings would support the observation that the critical segment for the assignment of LGS is proximal to or involves the proximal part of 8q24.1, but a review of published reports suggests that the aetiology of LGS may be a more complex issue.     

An XYY boy with short stature and a case of Klinefelter's syndrome (XXY) in a family with inversion 9

A patient with Klinefelter's syndrome and a boy with XYY sex chromosomes were both found to have a pericentric inversion of chromosome 9. An unusual feature of the XYY patient was that he presented because of short stature and disturbed behaviour. A family study showed that the patients were related and that there was an excess of males in the pedigree. Another member of the family was found to have some XYY cells in the blood.     

Translocation (Y;22) resulting in the loss of SHOX and isolated short stature

We report a 19-year-old woman with minor craniofacial anomalies, mild mental retardation, and foramina parietalia permagna (FPP) (OMIM 168500). Cytogenetic analysis showed a de novo interstitial chromosome 22 long arm duplication. FISH with a panel of chromosome 22q12-q13 bands-specific BAC clones refined the cytogenetic investigation, and restricted the duplicated segment to the q12 region. Mutation analysis of FPP genes identified an insertion mutation in the ALX4 gene (344insC) in the proband and her father with loss of function of the gene. The patient's phenotype is considered in the light of the results of the cytogenetic, FISH, and molecular investigations, and her features are compared with those of other patients with similar duplications. Finally, variable phenotypic findings due to different 22q duplicated chromosomal segments are discussed. Our report indicates that 22q12 interstitial duplications are associated with craniofacial anomalies and mild mental retardation, while life threatening malformations are usually not present. Although these phenotypic changes are common and non-specific, molecular study of our patient established more precise relationships between clinical findings and 22q duplicated region(s). This approach fosters better counseling of the families of patients with newly diagnosed, similar duplications.