Table 1

Summary of clinical features for affected individuals with HERC2 mutations



Publication and pedigree
IndividualGenderAge seen (years)SpeechWalked (years)Intellectual disabilityChildhood hypotoniaSeizuresNeuroimagingBlindnessGenotype (NM_004667.5)
This reportII:3F6 (died 7)NN++++YYCMD, ACCYc.13767_13770delTGAA
p.(Asn4589LysfsTer4598)
II:5M1.5 (died 4)NN++++YNCMD, ACCY
II:6F3.5NN++++YYCMD, ACCY
Harlalka et al: 1A9 VIII:7F39100 words4.3++YNNorN c.1781C>T, p.(Pro594Leu);
VIII:8M35<30 words4.3++/+++YNNKN
IX:1F24SS4++YNNKN
IX:6M17SS4++YYNKN
IX:7F19SS4++YNNorN
X:1F13.6<30 words4++YNNorN
X:2F12.610 words4++YNNKN
X:4F5.1NN++/+++YNACCN
X:5F6.7SS5++YNNKN
XI:2M7.8Limited3.5+YNNKN
XI:3M5.120 wordsN++YYACCN
Harlalka et al: 1B9 IX:8M17.8SS4.5+/++NKYACCN c.1781C>T, p.(Pro594Leu)
IX:10M16.8SS4+/++NKNNKN
IX:1F0.97NN++YYNKN
IX:2F2.7<10 wordsN+/++YNNKN
Puffenberger et al 8 Michigan sibship P1NK32NKa NKb +/++/+++c YNNKN c.1781C>T, p.(Pro594Leu)
Michigan sibship P2NK25NKa NKb +/++/+++c YNNKN
Michigan sibship P3NK31NKa NKb +/++/+++c NNNKN
Wisconsin sibship P1F7NKa NKb +/++/+++c NYNKN c.1781C>T, p.(Pro594Leu)
Wisconsin sibship P2F2NKa NKb +/++/+++c NYNKN
Puffernberger et al 8/Abraham et al 7 Puffenberger Ohio sibship P1/Abraham #1FPuffenberger: 40
Abrahams: 47
NKa NKb +/++/+++c NNNKd N c.1781C>T, p.(Pro594Leu)
Puffernberger Ohio sibship P2/Abraham #2MPuffenberger: 37
Abrahams: 43
NKa NKb +/++/+++c NNNKd N
Abraham et al 7 #3M23Few wordsNor++NNNKNKc.4625G>A, p.Arg1542His
#4F1110 words at 2 years, SS at 3 yearsNor+NYNN
Morice-Picard et al 10 ProbandM0, died 2 yearsNKNKNKYNKACC, CMD, megacisterna magnaNK (moderate retinal hypopigmentation)chr15: g. 28143765_28429460 del including OCA2 and HERC2
Proportion with feature (where known)Delayed speech:
20/20
Delayed walking: 18/20Intellectual disability: 27/27Childhood hypotonia:
19/26
Seizures:
9/27
Abn neuroimaging: 7/11Blindness: 3/26
  • NKa means details of individual cases not known; most had words by 2 years.

  • NKb means details of individual cases not known, walked at an average of 3.5 years (range 2.25–5.0 years).

  • +c means details of individual cases not known, range mild–moderate/severe.

  • NKd means details of individual cases not known, one sibling with normal MRI and one with mild cerebral atrophy.

  • + indicates mild; ++ indicates moderate; +++ indicates severe; ++++ indicates profound.

  • Abn, abnormal; ACC, absent corpus callosum; CMD, cortical migration defect; F, female; M, male; N, no; NK, not known; Nor, normal; SS, short sentence; Y, yes.