Case:Patient 1, female, 11 years old

DiseaseAssertion:Rett Syndrome - Atypical Variant

FamilyInfo:De Novo. Patient 1's parents were healthy. When Patient 1 was clinically examined, the head circumferences of her mother and father were 53 cm (P25) and 59 cm (P90), respectively. The parents had normal weight.

ParentalGenotype:Both parents were sequenced for Patient 1's mutation, and the deletion was not detected.

CasePresentingHPOs:HP:0001249, HP:0001513, HP:0001626, HP:0000256, HP:0010465, HP:0012758, HP:0000750, HP:0012433, HP:0002591, HP:0001250, HP:0020174, HP:0000316, HP:0000336, HP:0000431, HP:0000377, HP:0000470, HP:0001156, HP:0001500.

CaseHPOFreeText:

Patient history

@ birth - Patient 1 was born at 38 weeks of gestation after an uncomplicated pregnancy. Her weight was 3,390 g (P69), height 51 cm (P60), and her head circumference was 36 cm (P90).

@ 6 months - Patient 1 experienced developmental delay.

@ 9 months - Patient 1 sat without support.

@ 2 years - Patient 1 began to walk.

@ later on - Patient 1 presented with speech delay and behavioral disturbances. The behavioral disturbances were reduced by the drug risperidone.

@ early childhood - Patient 1 has been obese and appeared to display hyperphagia.

@ 8 years - Patient 1 developed precocious puberty.

@ 10 years - Patient 1 had her first epileptic seizure. Treatment with lamotrigine prevented further seizures. The seizures later became refractory to this treatment.

@ 10 years - Patient 1 presented with a height of 160 cm (P>97) and a head circumference of 59 cm (P>97). She had hypertelorism and prominent eyebrows. Her nasal bridge was broad and auricles were fleshy. In addition, Patient 1's neck was short and the fingers were short and wide.

Patient 1 has an intellectual disability, metabolic syndrome, and macrocephaly.

CaseNotHPOs:HP:0002540.

CaseNotHPOFreeText:Patient 1 sat without support at 9 months old. She walked at 2 years.

CasePreviousTesting:Patient 1 was given a conventional cytogenetic analysis. The chromosomal analyses (46,XX) and array CGH results (BlueGnome CytoChip ISCA 4×180K v1.0; Agilent Human Genome CGH Microarray 180K) were normal. Patient 1 was also given a methylation-specific MLPA to exclude a Temple syndrome, which is also characterized by weight gain and precocious puberty. In addition, Prader-Willi syndrome was ruled out by methylation testing. This syndrome is another imprinting disease causing obesity and intellectual disability.

PreviouslyPublished:Not previously published

GenotypingMethod:Whole-exome sequencing analysis of the entire exome was conducted for Patient 1. Whole-genome sequencing showed heterozygosity in Patient 1, which was confirmed by Sanger sequencing. Macrocephalic syndrome genes including PTEN, NSD1, NFIX, SETBP1, RAI1, and PHF6 were analyzed, and no additional variants of interest (pathogenic, likely pathogenic, or variants of uncertain significance) were observed.

Gene:MECP2

Variant:c. 1162_1172del (p. Pro388*), heterozygosity, frameshift.

HGVS:NM_004992.3

ClinVarID:Not found

CAID:CA1139667881

gnomAD:Not found

MultipleGeneVariants:Not provided